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1
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Koseoglu ND, Wang J, Anokye-Danso F, Amezcua Moreno J, Cha E, Fuchs F, Teed J, Yao J, Zhang Y, Ahima RS, Sachdeva MM. Association of serum adiponectin and leptin levels with inner retinal thickness among individuals with or without elevated HbA1c. Sci Rep 2025; 15:8498. [PMID: 40075217 PMCID: PMC11904190 DOI: 10.1038/s41598-025-93562-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Accepted: 03/07/2025] [Indexed: 03/14/2025] Open
Abstract
Inner retinal thinning precedes clinical evidence of retinopathy in prediabetes and diabetes mellitus (DM), and may contribute to retinopathy development and progression. Serum levels of the adipokines leptin and adiponectin are inversely related in the setting of impaired glucose homeostasis, but their potential association with inner retinal thickness is unknown. In this prospective study, both eyes from 24 individuals with prediabetes or type 2 DM (glycated hemoglobin [HbA1c] ≥ 5.7) and 16 controls (HbA1c < 5.7) underwent spectral-domain optical coherence tomography imaging of the macula, and thickness of the nerve fiber layer (NFL) and ganglion cell layer-inner plexiform layer (GCL-IPL) was analyzed in each subfield of the Early Treatment Diabetic Retinopathy Study grid. Serum samples were collected and metabolic factors, including adiponectin and leptin, were measured. Adjusted regression analyses revealed inverse associations of these adipokines with NFL thickness that did not differ between prediabetes/DM and controls, but differential positive associations of adiponectin with GCL-IPL thickness only in the prediabetes/DM group. The results of our pilot study suggest opposing roles for adiponectin and leptin in the retina, similar to their relationship in systemic disease, and suggest that serum adiponectin may represent a potential clinical biomarker for inner retinal thickness in patients with elevated HbA1c.
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Affiliation(s)
- Neslihan D Koseoglu
- Retina Division, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Jiangxia Wang
- Department of Biostatistics, Johns Hopkins Biostatistics Center, Johns Hopkins University, Baltimore, MD, USA
- Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA
| | - Frederick Anokye-Danso
- Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Jose Amezcua Moreno
- Retina Division, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Eumee Cha
- Retina Division, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Franklin Fuchs
- Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA
| | - Jacqueline Teed
- Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA
| | - Jianing Yao
- Department of Biostatistics, Johns Hopkins Biostatistics Center, Johns Hopkins University, Baltimore, MD, USA
| | - Yan Zhang
- Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA
| | - Rexford S Ahima
- Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Mira M Sachdeva
- Retina Division, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
- Wilmer Eye Institute, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Maumenee 748, Baltimore, MD, 21287, USA.
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Bigliassi M, Cabral DF, Evans AC. Improving brain health via the central executive network. J Physiol 2025. [PMID: 39856810 DOI: 10.1113/jp287099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Accepted: 01/06/2025] [Indexed: 01/27/2025] Open
Abstract
Cognitive and physical stress have significant effects on brain health, particularly through their influence on the central executive network (CEN). The CEN, which includes regions such as the dorsolateral prefrontal cortex, anterior cingulate cortex and inferior parietal lobe, is central to managing the demands of cognitively challenging motor tasks. Acute stress can temporarily reduce connectivity within the CEN, leading to impaired cognitive function and emotional states. However a rebound in these states often follows, driven by motivational signals through the mesocortical and mesolimbic pathways, which help sustain inhibitory control and task execution. Chronic exposure to physical and cognitive challenges leads to long-term improvements in CEN functionality. These changes are supported by neurochemical, structural and systemic adaptations, including mechanisms of tissue crosstalk. Myokines, adipokines, anti-inflammatory cytokines and gut-derived metabolites contribute to a biochemical environment that enhances neuroplasticity, reduces neuroinflammation and supports neurotransmitters such as serotonin and dopamine. These processes strengthen CEN connectivity, improve self-regulation and enable individuals to adopt and sustain health-optimizing behaviours. Long-term physical activity not only enhances inhibitory control but also reduces the risk of age-related cognitive decline and neurodegenerative diseases. This review highlights the role of progressive physical stress through exercise as a practical approach to strengthening the CEN and promoting brain health, offering a strategy to improve cognitive resilience and emotional well-being across the lifespan.
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Affiliation(s)
- Marcelo Bigliassi
- Department of Teaching and Learning, Florida International University, Miami, Florida, USA
| | - Danylo F Cabral
- Department of Neurology, Harvard Medical School, Boston, Massachusetts, USA
| | - Amanda C Evans
- Functional Flow Solutions LLC, Albuquerque, New Mexico, USA
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Barbalho SM, Laurindo LF, de Oliveira Zanuso B, da Silva RMS, Gallerani Caglioni L, Nunes Junqueira de Moraes VBF, Fornari Laurindo L, Dogani Rodrigues V, da Silva Camarinha Oliveira J, Beluce ME, Penteado Detregiachi CR, Barbalho Lamas C, dos Santos Haber JF, Cavallari Strozze Catharin VM, Quesada K, Tanaka M, Valenti VE. AdipoRon's Impact on Alzheimer's Disease-A Systematic Review and Meta-Analysis. Int J Mol Sci 2025; 26:484. [PMID: 39859201 PMCID: PMC11765103 DOI: 10.3390/ijms26020484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Revised: 12/28/2024] [Accepted: 01/03/2025] [Indexed: 01/27/2025] Open
Abstract
Alzheimer's disease (AD) remains a leading cause of cognitive decline and mortality worldwide, characterized by neurodegeneration, synaptic deficiencies, and neuroinflammation. Despite advancements in early detection, diagnosis, and treatment, AD presents substantial challenges due to its complex pathology, heterogeneity, and the limited efficacy of current therapies. Consequently, there is a pressing need for novel therapeutic agents to target the multifaceted aspects of AD pathology, enhance current treatments, and minimize adverse effects. AdipoRon, an adiponectin receptor agonist, has garnered interest for its potential neuroprotective effects, including reducing neuroinflammation, improving mitochondrial function, and mitigating tau hyperphosphorylation. This review aimed to evaluate the effects of AdipoRon-based adiponectin replacement therapy against AD, using a comprehensive approach grounded in the PICO framework-Population, Intervention, Comparison, and Outcomes. A total of six studies were reviewed, including in vitro and in vivo investigations examining AdipoRon's impact on various AD models. These studies involved different cell lines and transgenic mouse models, assessing various outcomes such as cognitive function, neuroinflammation, tau phosphorylation, synaptic deficiencies, and relevant molecular pathways. By synthesizing data from these studies, our review thoroughly explains AdipoRon's neuroprotective effects, mechanisms of action, and potential as a therapeutic agent for AD. This analysis aims to highlight the current state of knowledge, identify gaps in the research, and suggest directions for future studies and clinical applications.
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Affiliation(s)
- Sandra Maria Barbalho
- Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, São Paulo, Brazil; (S.M.B.); (L.F.L.)
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, São Paulo, Brazil
- Department of Biochemistry and Nutrition, School of Food and Technology of Marília (FATEC), Marília 17500-000, São Paulo, Brazil
- UNIMAR Charity Hospital, Universidade de Marília (UNIMAR), Marília 17525-902, São Paulo, Brazil
| | - Lucas Fornari Laurindo
- Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, São Paulo, Brazil; (S.M.B.); (L.F.L.)
- Department of Biochemistry and Pharmacology, School of Medicine, Faculdade de Medicina de Marília (FAMEMA), Marília 17519-030, São Paulo, Brazil
- Department of Administration, Associate Degree in Hospital Management, Universidade de Marília (UNIMAR), Marília 17525-902, São Paulo, Brazil
| | - Bárbara de Oliveira Zanuso
- Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, São Paulo, Brazil; (S.M.B.); (L.F.L.)
| | - Rebeca Maria Siqueira da Silva
- Department of Biochemistry and Pharmacology, School of Medicine, Faculdade de Medicina de Marília (FAMEMA), Marília 17519-030, São Paulo, Brazil
| | - Lívia Gallerani Caglioni
- Department of Biochemistry and Pharmacology, School of Medicine, Faculdade de Medicina de Marília (FAMEMA), Marília 17519-030, São Paulo, Brazil
| | | | - Lívia Fornari Laurindo
- Department of Biochemistry and Pharmacology, School of Medicine, Faculdade de Medicina de São José do Rio Preto (FAMERP), São José do Rio Preto 15090-000, São Paulo, Brazil
| | - Victória Dogani Rodrigues
- Department of Biochemistry and Pharmacology, School of Medicine, Faculdade de Medicina de Marília (FAMEMA), Marília 17519-030, São Paulo, Brazil
| | - Jéssica da Silva Camarinha Oliveira
- Department of Biochemistry and Pharmacology, School of Medicine, Faculdade de Medicina de Marília (FAMEMA), Marília 17519-030, São Paulo, Brazil
| | - Maria Eduarda Beluce
- Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, São Paulo, Brazil; (S.M.B.); (L.F.L.)
| | - Cláudia Rucco Penteado Detregiachi
- Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, São Paulo, Brazil; (S.M.B.); (L.F.L.)
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, São Paulo, Brazil
| | - Caroline Barbalho Lamas
- Department of Gerontology, School of Gerontology, Universidade Federal de São Carlos (UFSCar), São Carlos 13565-905, São Paulo, Brazil
| | - Jesselina Francisco dos Santos Haber
- Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, São Paulo, Brazil; (S.M.B.); (L.F.L.)
| | - Virgínia Maria Cavallari Strozze Catharin
- Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, São Paulo, Brazil; (S.M.B.); (L.F.L.)
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, São Paulo, Brazil
| | - Karina Quesada
- Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, São Paulo, Brazil; (S.M.B.); (L.F.L.)
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, São Paulo, Brazil
| | - Masaru Tanaka
- Danube Neuroscience Research Laboratory, HUN-REN-SZTE Neuroscience Research Group, Hungarian Research Network, University of Szeged (HUN-REN-SZTE), Tisza Lajos Krt. 113, H-6725 Szeged, Hungary
| | - Vitor Engrácia Valenti
- Autonomic Nervous System Center, School of Philosophy and Sciences, São Paulo State University, Marília 17525-902, São Paulo, Brazil
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Trevisi E, Cattaneo L, Piccioli-Cappelli F, Mezzetti M, Minuti A. International Symposium on Ruminant Physiology: The immunometabolism of transition dairy cows from dry-off to early lactation: lights and shadows. J Dairy Sci 2025:S0022-0302(24)01444-9. [PMID: 39778800 DOI: 10.3168/jds.2024-25790] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2024] [Accepted: 12/03/2024] [Indexed: 01/11/2025]
Abstract
The mismatch between the nutrient intake from the diet and the output by the mammary gland causes a negative energy balance in transition dairy cows, that, if excessive, can promote several metabolic disorders. Other relevant phenomena occur during transition, such as inflammation at calving and changes in immunocompetence, redox balance, and mineral metabolism. Despite the efforts, some aspects of the adaptive mechanisms observed in the transition period still need to be clarified. For instance, alterations of physiological responses even before the dry-off or during the dry period can affect the success of the whole transition period in certain cows. In this context, the mechanism regulating the inflammatory response around calving may play a pivotal role, as suggested by the variety of factors influencing it and its consequences, particularly feed intake depression, that can amplify and anticipate the negative energy balance. When this mechanism derails is still unclear, but detecting the triggers of diverted or abnormal physiological responses and where they stem (e.g., liver, rumen and gut epithelia, uterus, or mammary gland) will help to discover the weak points in the immune system and the possible ways of restoring it. Furthermore, the postpartum healthy cow appears to have an acute phase response at the liver level, despite a decrease in circulating proinflammatory cytokines. What is physiological and what is pathological in this context? To understand the latter, finding markers of an unsuccessful transition period that go beyond the energy deficit would be advisable. Future efforts should be dedicated to clarifying the causes of the acute phase response at calving, exploiting the potential of the system biology. Moreover, it would be helpful, for both basic and applied research, to define biomarkers associated with pathological responses (i.e., cytokines and acute phase proteins) and to introduce in the genetic selection phenotypes related to the ability of cows to adapt to the immunometabolic stress typical of the transition period.
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Affiliation(s)
- Erminio Trevisi
- Department of Animal Science, Food and Nutrition (DIANA), Faculty of Agricultural, Food and Environmental Sciences, Università Cattolica del Sacro Cuore, 29122 Piacenza, Italy; Romeo and Enrica Invernizzi Research Center for Sustainable Dairy Production of the Università Cattolica del Sacro Cuore (CREI), 29122 Piacenza, Italy.
| | - Luca Cattaneo
- Department of Animal Science, Food and Nutrition (DIANA), Faculty of Agricultural, Food and Environmental Sciences, Università Cattolica del Sacro Cuore, 29122 Piacenza, Italy
| | - Fiorenzo Piccioli-Cappelli
- Department of Animal Science, Food and Nutrition (DIANA), Faculty of Agricultural, Food and Environmental Sciences, Università Cattolica del Sacro Cuore, 29122 Piacenza, Italy
| | - Matteo Mezzetti
- Department of Animal Science, Food and Nutrition (DIANA), Faculty of Agricultural, Food and Environmental Sciences, Università Cattolica del Sacro Cuore, 29122 Piacenza, Italy
| | - Andrea Minuti
- Department of Animal Science, Food and Nutrition (DIANA), Faculty of Agricultural, Food and Environmental Sciences, Università Cattolica del Sacro Cuore, 29122 Piacenza, Italy
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Perdaens O, van Pesch V. Should We Consider Neurodegeneration by Itself or in a Triangulation with Neuroinflammation and Demyelination? The Example of Multiple Sclerosis and Beyond. Int J Mol Sci 2024; 25:12637. [PMID: 39684351 PMCID: PMC11641818 DOI: 10.3390/ijms252312637] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Revised: 11/20/2024] [Accepted: 11/20/2024] [Indexed: 12/18/2024] Open
Abstract
Neurodegeneration is preeminent in many neurological diseases, and still a major burden we fail to manage in patient's care. Its pathogenesis is complicated, intricate, and far from being completely understood. Taking multiple sclerosis as an example, we propose that neurodegeneration is neither a cause nor a consequence by itself. Mitochondrial dysfunction, leading to energy deficiency and ion imbalance, plays a key role in neurodegeneration, and is partly caused by the oxidative stress generated by microglia and astrocytes. Nodal and paranodal disruption, with or without myelin alteration, is further involved. Myelin loss exposes the axons directly to the inflammatory and oxidative environment. Moreover, oligodendrocytes provide a singular metabolic and trophic support to axons, but do not emerge unscathed from the pathological events, by primary myelin defects and cell apoptosis or secondary to neuroinflammation or axonal damage. Hereby, trophic failure might be an overlooked contributor to neurodegeneration. Thus, a complex interplay between neuroinflammation, demyelination, and neurodegeneration, wherein each is primarily and secondarily involved, might offer a more comprehensive understanding of the pathogenesis and help establishing novel therapeutic strategies for many neurological diseases and beyond.
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Affiliation(s)
- Océane Perdaens
- Neurochemistry Group, Institute of NeuroScience, Université Catholique de Louvain (UCLouvain), 1200 Brussels, Belgium;
| | - Vincent van Pesch
- Neurochemistry Group, Institute of NeuroScience, Université Catholique de Louvain (UCLouvain), 1200 Brussels, Belgium;
- Department of Neurology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain (UCLouvain), 1200 Brussels, Belgium
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Shaikh I, Bhatt LK. Targeting Adipokines: A Promising Therapeutic Strategy for Epilepsy. Neurochem Res 2024; 49:2973-2987. [PMID: 39060767 DOI: 10.1007/s11064-024-04219-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Revised: 07/17/2024] [Accepted: 07/22/2024] [Indexed: 07/28/2024]
Abstract
Epilepsy affects 65 million people globally and causes neurobehavioral, cognitive, and psychological defects. Although research on the disease is progressing and a wide range of treatments are available, approximately 30% of people have refractory epilepsy that cannot be managed with conventional medications. This underlines the importance of further understanding the condition and exploring cutting-edge targets for treatment. Adipokines are peptides secreted by adipocyte's white adipose tissue, involved in controlling food intake and metabolism. Their regulatory functions in the central nervous system (CNS) are multifaceted and identified in several physiology and pathologies. Adipokines play a role in oxidative stress and neuroinflammation which are associated with brain degeneration and connected neurological diseases. This review aims to highlight the potential impacts of leptin, adiponectin, apelin, vaspin, visfatin, and chimerin in the pathogenesis of epilepsy.
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Affiliation(s)
- Iqraa Shaikh
- Department of Pharmacology, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, Vile Parle (W), Mumbai, India
| | - Lokesh Kumar Bhatt
- Department of Pharmacology, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, Vile Parle (W), Mumbai, India.
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Ghosh P, Fontanella RA, Scisciola L, Taktaz F, Pesapane A, Basilicata MG, Tortorella G, Matacchione G, Capuano A, Vietri MT, Selvaggi F, Paolisso G, Barbieri M. Obesity-induced neuronal senescence: Unraveling the pathophysiological links. Ageing Res Rev 2024; 101:102533. [PMID: 39368666 DOI: 10.1016/j.arr.2024.102533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Revised: 07/24/2024] [Accepted: 09/30/2024] [Indexed: 10/07/2024]
Abstract
Obesity is one of the most prevalent and increasing metabolic disorders and is considered one of the twelve risk factors for dementia. Numerous studies have demonstrated that obesity induces pathophysiological changes leading to cognitive decline; however, the underlying molecular mechanisms are yet to be fully elucidated. Various biochemical processes, including chronic inflammation, oxidative stress, insulin resistance, dysregulation of lipid metabolism, disruption of the blood-brain barrier, and the release of adipokines have been reported to contribute to the accumulation of senescent neurons during obesity. These senescent cells dysregulate neuronal health and function by exhibiting a senescence-associated secretory phenotype, inducing neuronal inflammation, deregulating cellular homeostasis, causing mitochondrial dysfunction, and promoting microglial infiltration. These factors act as major risks for the occurrence of neurodegenerative diseases and cognitive decline. This review aims to focus on how obesity upregulates neuronal senescence and explores both pharmacological and non-pharmacological interventions for preventing cognitive impairments, thus offering new insights into potential therapeutic strategies.
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Affiliation(s)
- Puja Ghosh
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Rosaria Anna Fontanella
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Lucia Scisciola
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Fatemeh Taktaz
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Ada Pesapane
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Manuela Giovanna Basilicata
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Giovanni Tortorella
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
| | | | - Annalisa Capuano
- Department of Experimental Medicine - Section of Pharmacology "L. Donatelli", University of Campania "Luigi Vanvitelli", Naples 80138, Italy
| | - Maria Teresa Vietri
- Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Via L. De Crecchio, Naples 80138, Italy; UOC Clinical and Molecular Pathology, AOU University of Campania "Luigi Vanvitelli", Naple 80138, Italy
| | - Francesco Selvaggi
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Giuseppe Paolisso
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy; UniCamillus, International Medical University, Rome, Italy
| | - Michelangela Barbieri
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy.
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Rebelo F, de Moura CO, Ranquine LG, Teixeira TDM, Ribas MTN, Vitorino RS, de Abranches AD, Costa RP, de Britto JAA, Marano D, Soares FVM, Junqueira-Marinho MDF, de Sousa CAM, Franco-Sena AB, Nardi AE, El-Bacha T, Moreira MEL. Plasma and breast milk adipokines in women across the first year postpartum and their association with maternal depressive symptoms and infant neurodevelopment: Protocol for the APPLE prospective cohort study. PLoS One 2024; 19:e0310847. [PMID: 39453947 PMCID: PMC11508165 DOI: 10.1371/journal.pone.0310847] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Accepted: 09/04/2024] [Indexed: 10/27/2024] Open
Abstract
INTRODUCTION Adiponectin and leptin play important roles in the central nervous system. During the postpartum period, there is a need for a better understanding of the relationship between these cytokines and the neurological development of the infant, as well as their influence on preventing maternal depressive symptoms. OBJECTIVES To assess the correlation between adiponectin and leptin in maternal plasma and breast milk and their association with: infant neurodevelopment at 6 and 12 months of age; and maternal mental health over the first year postpartum. METHODS Prospective cohort study with four follow-up. Mothers and their newborns are recruited within the first 15 days postpartum (baseline). Follow-up visits occur at 2, 6, and 12 months postpartum. Visits include blood and breast milk collection, application of the Edinburgh Postnatal Depression Scale and Beck Depression Inventory to assess maternal mental health, application of the Bayley-III scale for infant developmental assessment, maternal and infant anthropometry and body composition, evaluation of reproductive history, mother-infant bonding, breastfeeding, consumption of ultra-processed foods, sleep quality, and socio-economic and demographic data. RESULTS The research received funds in August 2022, and participant recruitment began in September 2022. The sample size will consist of 95 mother-child pairs. As of September 2023, 68 participants have been recruited. CONCLUSION The project will provide insights into the association between adiponectin and leptin with postpartum depression and infant neurodevelopment, ultimately promoting improved care and quality of life for these groups. Additionally, it will provide data on the type of delivery, infant physical growth, maternal and infant body composition changes, sleep quality, consumption of ultra-processed foods, and maternal metabolic health, including vitamin D metabolites, oxidized polyunsaturated fatty acid metabolites, phospholipid species and triacylglycerols, which are of significant relevance to public health and, when interconnected, may yield important results and contribute to the existing literature. TRIAL REGISTRATION Name of the registry: Brazilian Clinical Trials Registry (ReBec). Registration number: RBR-9hcby8c.
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Affiliation(s)
- Fernanda Rebelo
- Instituto Nacional de Saúde da Mulher, Unidade de Pesquisa Clínica, da Criança e do Adolescente Fernandes Figueira, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
| | - Cintia Oliveira de Moura
- Instituto Nacional de Saúde da Mulher, Programa de Pós-graduação em Pesquisa Aplicada à Saúde da Criança e da Mulher, da Criança e do Adolescente Fernandes Figueira, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
| | - Layla Galvão Ranquine
- Instituto de Nutrição Josué de Castro, LeBioME-Bioactives, Mitochondrial and Placental Metabolism Core, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
| | - Thaisa de Mattos Teixeira
- Instituto Nacional de Saúde da Mulher, Programa de Pós-graduação em Saúde da Criança e da Mulher, da Criança e do Adolescente Fernandes Figueira, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
| | - Mariana Terra Nunes Ribas
- Instituto de Nutrição Josué de Castro, LeBioME-Bioactives, Mitochondrial and Placental Metabolism Core, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
| | - Raquel Santiago Vitorino
- Instituto Nacional de Saúde da Mulher, Programa de Pós-graduação em Saúde da Criança e da Mulher, da Criança e do Adolescente Fernandes Figueira, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
| | - Andrea Dunshee de Abranches
- Instituto Nacional de Saúde da Mulher, Unidade de Pesquisa Clínica, da Criança e do Adolescente Fernandes Figueira, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
| | - Roozemeria Pereira Costa
- Instituto Nacional de Saúde da Mulher, Unidade de Pesquisa Clínica, da Criança e do Adolescente Fernandes Figueira, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
| | - José Augusto Alves de Britto
- Instituto Nacional de Saúde da Mulher, Área da Pediatria–Unidade Ambulatorial, da Criança e do Adolescente Fernandes Figueira, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
| | - Daniele Marano
- Instituto Nacional de Saúde da Mulher, Unidade de Pesquisa Clínica, da Criança e do Adolescente Fernandes Figueira, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
| | - Fernanda Valente Mendes Soares
- Instituto Nacional de Saúde da Mulher, Unidade de Pesquisa Clínica, da Criança e do Adolescente Fernandes Figueira, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
| | - Maria de Fátima Junqueira-Marinho
- Instituto Nacional de Saúde da Mulher, Unidade de Pesquisa Clínica, da Criança e do Adolescente Fernandes Figueira, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
| | - Carlos Augusto Moreira de Sousa
- Faculdade de Ciências Médicas, Departamento de Tecnologias da Informação e Educação em Saúde, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
| | - Ana Beatriz Franco-Sena
- Faculdade de Nutrição Emília de Jesus Ferreiro, Departamento de Nutrição Social, Universidade Federal Fluminense, Niterói, RJ, Brazil
| | - Antônio Egídio Nardi
- Instituto de Psiquiatria, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
| | - Tatiana El-Bacha
- Instituto de Nutrição Josué de Castro, LeBioME-Bioactives, Mitochondrial and Placental Metabolism Core, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
| | - Maria Elisabeth Lopes Moreira
- Instituto Nacional de Saúde da Mulher, Unidade de Pesquisa Clínica, da Criança e do Adolescente Fernandes Figueira, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
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9
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Jia Z, Qiu F, He Y, Chen H, Yang C, Liu H, Zheng T, Xu S, Wang S, Li Y. The fetal origins of metabolic health: exploring the association between newborn biological age and metabolism hormones in childhood. BMC Med 2024; 22:429. [PMID: 39379967 PMCID: PMC11462715 DOI: 10.1186/s12916-024-03629-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 09/11/2024] [Indexed: 10/10/2024] Open
Abstract
BACKGROUND Telomere length (TL), mitochondrial DNA copy number (mtDNAcn), and DNA methylation age (DNAmAge) are common aging biomarkers. However, research on the associations between these three markers at birth and subsequent metabolic status was limited. This study aimed to evaluate the association between TL, mtDNAcn, and DNAmAge in newborns and the variation in metabolic hormones of children at 3 years old. METHODS This research involved 895 mother-child pairs from a birth cohort in China, with TL and mtDNAcn measured using quantitative real-time PCR, DNA methylation (DNAm) assessed using Infinium MethylationEPIC Beadchip, and DNAm age (DNAmAge) determined using Horvath's epigenetic clock. Insulin and leptin levels were measured via electrochemiluminescence assay. Multivariable adjusted linear regression and restricted cubic spline (RCS) analysis were utilized to examine the association between aging markers and metabolic hormones. RESULTS The linear regression analysis indicated the percentage change of metabolism hormones for per doubling of aging biomarkers alterations and found significant associations between DNAmAge and insulin levels (adjusted percent change (95% CI), - 13.22 (- 23.21 to - 1.94)), TL and leptin levels (adjusted percent change (95% CI), 15.32 (1.32 to 31.24)), and mtDNAcn and leptin levels (adjusted percent change (95% CI), - 14.13 (- 21.59 to - 5.95)). The RCS analysis revealed significant non-linear associations between TL (Ln transformed) and insulin (Ln transformed) (P = 0.024 for nonlinearity), as well as DNAmAge (Ln transformed) and leptin (Ln transformed) (P = 0.043 for nonlinearity). Specifically, for TL and insulin, a positive association was observed when TL (Ln transformed) was less than - 0.05, which transitioned to an inverse association when TL (Ln transformed) was greater than - 0.05. Regarding DNAmAge and leptin, there was a sharp decline when DNAmAge (Ln transformed) was less than - 1.35, followed by a plateau between - 1.35 and - 0.67 and then a further decline when DNAmAge (Ln transformed) was greater than - 0.67. CONCLUSIONS In this prospective birth cohort study, variation in metabolic hormones of children at 3 years old was associated with TL, mtDNAcn, and DNAmAge at birth. These findings suggested that TL, mtDNAcn, and DNAmAge might play a role in the biological programming of metabolic health from birth.
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Affiliation(s)
- Zhenxian Jia
- Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, Hubei, 430030, China
| | - Feng Qiu
- Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, Hubei, 430030, China
| | - Yujie He
- Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, Hubei, 430030, China
| | - Huan Chen
- Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, Hubei, 430030, China
| | - Chenhui Yang
- Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, Hubei, 430030, China
| | - Hongxiu Liu
- Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, Hubei, 430030, China
| | - Tongzhang Zheng
- Department of Epidemiology, School of Public Health, Brown University, Providence, RI, 02912, USA
| | - Shunqing Xu
- Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, Hubei, 430030, China.
- School of Environmental Science and Engineering, Hainan University, Haikou, Hainan, 570228, China.
| | - Shiqiong Wang
- Institute of Maternal and Children Health, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, 430016, China.
| | - Yuanyuan Li
- Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, Hubei, 430030, China.
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10
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Al-Darsani Z, Banack HR, Ziegler MN, Rapp SR, Corrada MM, Odegaard AO. DXA-Measured Abdominal Adipose Depots and Structural Brain Integrity in Postmenopausal Women. Alzheimer Dis Assoc Disord 2024; 38:305-310. [PMID: 39129431 DOI: 10.1097/wad.0000000000000642] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Accepted: 07/14/2024] [Indexed: 08/13/2024]
Abstract
BACKGROUND This study extends prior research from the MRI substudy of the Women's Health Initiative Memory Study (WHIMS-MRI) linking BMI to reduced brain atrophy and ischemic lesion load by examining DXA-based measurements of total body fat, total abdominal adipose tissue (TAT), abdominal visceral (VAT) and subcutaneous (SAT) adipose tissue, gynoid fat, and overall leg fat. METHODS The analytic sample consisted of 61 postmenopausal women (baseline mean age 69.5 [3.6]) enrolled in WHIMS-MRI who had undergone DXA scans. DXA scans were completed at years 0, 3, and 6, and MRI scans were conducted ~8 years after baseline. Adjusted linear regression models were used to analyze the association between adiposity averaged across the 3-time points and volumes of brain regions previously linked to dementia. RESULTS Higher levels of total body fat, TAT, VAT, SAT, gynoid, and overall leg fat were associated with larger hippocampal volume (β 0.02 [95% CI, 0.004-0.04]; 0.11 [0.02-0.21]; 0.26 [0.04-0.47]; 0.18 [0.03-0.33]; 0.18 [0.05-0.30]; 0.07 [0.009-0.12], respectively). No other significant associations were observed. CONCLUSION Higher levels of adiposity were positively associated with hippocampal volume. Additional research with larger sample sizes is needed to ascertain the significance of this association.
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Affiliation(s)
- Zeinah Al-Darsani
- Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA
- Department of Epidemiology and Biostatistics, Temple University College of Public Health, Philadelphia, PA
| | - Hailey R Banack
- Epidemiology Division, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada
| | - Mallory N Ziegler
- Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY
| | - Stephen R Rapp
- Department of Psychiatry & Behavioral Medicine, Wake Forest University School of Medicine, Winston-Salem, NC
| | - Maria M Corrada
- Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA
- Department of Epidemiology and Biostatistics, University of California, Irvine, CA
- Department of Neurology, University of California, Irvine, CA
| | - Andrew O Odegaard
- Department of Epidemiology and Biostatistics, University of California, Irvine, CA
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11
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Czechowski P, Hagemann T, Ghosh A, Sun W, Dong H, Noé F, Niersmann C, Reinisch I, Wolfrum C, Herder C, Dietrich A, Blüher M, Hoffmann A. Expression of Intelectin-1, also known as Omentin-1, is related to clinical phenotypes such as overweight, obesity, insulin resistance, and changes after bariatric surgery. Sci Rep 2024; 14:22286. [PMID: 39333229 PMCID: PMC11437189 DOI: 10.1038/s41598-024-72720-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Accepted: 09/10/2024] [Indexed: 09/29/2024] Open
Abstract
Intelectin-1 (ITLN1; also Omentin-1, OMNT1) is secreted by adipose tissue (AT) and plays an important role in glucose metabolism regulation, with links to obesity-associated diseases. ITLN1 activity so far has rarely been investigated using RNA-sequencing and in larger cohorts. We evaluated ITLN1 expression among three clinical cohorts of the Leipzig Obesity BioBank-a cross-sectional cohort comprising of 1480 people, a cohort of people with metabolically healthy or unhealthy obesity (31 insulin-sensitive, 42 insulin-resistant individuals with obesity), and a longitudinal two-step bariatric surgery cohort (n = 65). We hypothesized that AT ITLN1 expression is associated with serum omentin-1, clinical parameters associated with obesity, and with weight loss after bariatric surgery. We also investigated the correlation of AT ITLN1 expression with genes related to inflammatory response, lipid metabolism, obesity, and regulation of energy balance. Likewise, we inspected gene group expression and metabolic pathways associated with ITLN1 expression using gene set enrichment and gene correlation analysis. We show that ITLN1 expression differs in VAT and SAT, and should therefore be analyzed separately. Furthermore, ITLN1 expression increases with VAT tissue mass, but is negatively affected by AT tissue dysfunction among individuals with unhealthy obesity, corroborated by interplay with genes related to tissue inflammation. Gene set enrichment and gene correlation analysis of ITLN1 expression suggest that AT ITLN1 expression is related to local inflammatory processes in AT, but also in processes such as regulation of appetite, energy balance, and maintenance of body weight.
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Affiliation(s)
- Paul Czechowski
- Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig and University Hospital Leipzig, Philipp-Rosenthal-Straße 27, 04103, Leipzig, Germany.
| | - Tobias Hagemann
- Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig and University Hospital Leipzig, Philipp-Rosenthal-Straße 27, 04103, Leipzig, Germany
| | - Adhideb Ghosh
- Institute of Food, Nutrition and Health, ETH Zurich, Schmelzbergstrasse 9, 8092, Zurich, Switzerland
| | - Wenfei Sun
- Institute of Food, Nutrition and Health, ETH Zurich, Schmelzbergstrasse 9, 8092, Zurich, Switzerland
| | - Hua Dong
- Institute of Food, Nutrition and Health, ETH Zurich, Schmelzbergstrasse 9, 8092, Zurich, Switzerland
| | - Falko Noé
- Institute of Food, Nutrition and Health, ETH Zurich, Schmelzbergstrasse 9, 8092, Zurich, Switzerland
| | - Corinna Niersmann
- Deutsche Diabetes-Zentrum, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Institute for Clinical Diabetology, Auf'm Hennekamp 65, 40225, Düsseldorf, Germany
- Deutsches Zentrum für Diabetesforschung, Ingolstädter Landstraße 1, 85764, Oberschleißheim, Germany
| | - Isabel Reinisch
- Institute of Food, Nutrition and Health, ETH Zurich, Schmelzbergstrasse 9, 8092, Zurich, Switzerland
| | - Christian Wolfrum
- Institute of Food, Nutrition and Health, ETH Zurich, Schmelzbergstrasse 9, 8092, Zurich, Switzerland
| | - Christian Herder
- Deutsche Diabetes-Zentrum, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Institute for Clinical Diabetology, Auf'm Hennekamp 65, 40225, Düsseldorf, Germany
- Deutsches Zentrum für Diabetesforschung, Ingolstädter Landstraße 1, 85764, Oberschleißheim, Germany
- Department of Endocrinology and Diabetology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University, Moorenstraße 5, 40225, Düsseldorf, Germany
| | - Arne Dietrich
- Clinic and Outpatient Department for Visceral, Transplantation, Thoracic, and Vascular Surgery, Leipzig University Hospital, Liebigstraße 20, Haus 4, 04103, Leipzig, Germany
| | - Matthias Blüher
- Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig and University Hospital Leipzig, Philipp-Rosenthal-Straße 27, 04103, Leipzig, Germany
- Department of Endocrinology, Nephrology, Rheumatology, Leipzig University Hospital, Liebigstraße 20, Haus 4, Leipzig, 04103, Germany
| | - Anne Hoffmann
- Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig and University Hospital Leipzig, Philipp-Rosenthal-Straße 27, 04103, Leipzig, Germany
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12
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Mączka K, Stasiak O, Przybysz P, Grymowicz M, Smolarczyk R. The Impact of the Endocrine and Immunological Function of Adipose Tissue on Reproduction in Women with Obesity. Int J Mol Sci 2024; 25:9391. [PMID: 39273337 PMCID: PMC11395521 DOI: 10.3390/ijms25179391] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Revised: 08/21/2024] [Accepted: 08/27/2024] [Indexed: 09/15/2024] Open
Abstract
Obesity, which leads to metabolic dysregulation and body function impairment, emerges as one of the pressing health challenges worldwide. Excessive body fat deposits comprise a dynamic and biologically active organ possessing its own endocrine function. One of the mechanisms underlying the pathophysiology of obesity is low-grade systemic inflammation mediated by pro-inflammatory factors such as free fatty acids, lipopolysaccharides, adipokines (including leptin, resistin and visfatin) and cytokines (TNF-α, IL-1β, Il-6), which are secreted by adipose tissue. Together with obesity-induced insulin resistance and hyperandrogenism, the exacerbated immune response has a negative impact on the hypothalamic-pituitary-gonadal axis at all levels and directly affects reproduction. In women, it results in disrupted ovarian function, irregular menstrual cycles and anovulation, contributing to infertility. This review focuses on the abnormal intracellular communication, altered gene expression and signaling pathways activated in obesity, underscoring its multifactorial character and consequences at a molecular level. Extensive presentation of the complex interplay between adipokines, cytokines, immune cells and neurons may serve as a foundation for future studies in search of potential sites for more targeted treatment of reproductive disorders related to obesity.
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Affiliation(s)
- Katarzyna Mączka
- Department of Gynecological Endocrinology, Medical University of Warsaw, 00-315 Warsaw, Poland
- Doctoral School, Medical University of Warsaw, 02-091 Warsaw, Poland
| | - Olga Stasiak
- Department of Gynecological Endocrinology, Medical University of Warsaw, 00-315 Warsaw, Poland
| | - Paulina Przybysz
- Department of Gynecological Endocrinology, Medical University of Warsaw, 00-315 Warsaw, Poland
| | - Monika Grymowicz
- Department of Gynecological Endocrinology, Medical University of Warsaw, 00-315 Warsaw, Poland
| | - Roman Smolarczyk
- Department of Gynecological Endocrinology, Medical University of Warsaw, 00-315 Warsaw, Poland
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13
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Weijie Z, Meng Z, Chunxiao W, Lingjie M, Anguo Z, Yan Z, Xinran C, Yanjiao X, Li S. Obesity-induced chronic low-grade inflammation in adipose tissue: A pathway to Alzheimer's disease. Ageing Res Rev 2024; 99:102402. [PMID: 38977081 DOI: 10.1016/j.arr.2024.102402] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Revised: 06/19/2024] [Accepted: 06/30/2024] [Indexed: 07/10/2024]
Abstract
Alzheimer's disease (AD) is a leading cause of cognitive impairment worldwide. Overweight and obesity are strongly associated with comorbidities, such as hypertension, diabetes, and insulin resistance (IR), which contribute substantially to the development of AD and subsequent morbidity and mortality. Adipose tissue (AT) is a highly dynamic organ composed of a diverse array of cell types, which can be classified based on their anatomic localization or cellular composition. The expansion and remodeling of AT in the context of obesity involves immunometabolic and functional shifts steered by the intertwined actions of multiple immune cells and cytokine signaling within AT, which contribute to the development of metabolic disorders, IR, and systemic markers of chronic low-grade inflammation. Chronic low-grade inflammation, a prolonged, low-dose stimulation by specific immunogens that can progress from localized sites and affect multiple organs throughout the body, leads to neurodystrophy, increased apoptosis, and disruption of homeostasis, manifesting as brain atrophy and AD-related pathology. In this review, we sought to elucidate the mechanisms by which AT contributes to the onset and progression of AD in obesity through the mediation of chronic low-grade inflammation, particularly focusing on the roles of adipokines and AT-resident immune cells.
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Affiliation(s)
- Zhai Weijie
- Department of Neurology and Neuroscience Center, The First Hospital of Jilin University, Jilin University, Changchun, China; Cognitive Center, Department of Neurology, The First Hospital of Jilin University, Jilin University, Changchun, China
| | - Zhao Meng
- Department of Neurology and Neuroscience Center, The First Hospital of Jilin University, Jilin University, Changchun, China; Cognitive Center, Department of Neurology, The First Hospital of Jilin University, Jilin University, Changchun, China
| | - Wei Chunxiao
- Department of Neurology and Neuroscience Center, The First Hospital of Jilin University, Jilin University, Changchun, China; Cognitive Center, Department of Neurology, The First Hospital of Jilin University, Jilin University, Changchun, China
| | - Meng Lingjie
- Department of Neurology and Neuroscience Center, The First Hospital of Jilin University, Jilin University, Changchun, China; Cognitive Center, Department of Neurology, The First Hospital of Jilin University, Jilin University, Changchun, China
| | - Zhao Anguo
- Department of Urology, Dushu Lake Hospital Affiliated to Soochow University, Medical Center of Soochow University, Suzhou Dushu Lake Hospital, Suzhou 215000 China
| | - Zhang Yan
- Department of Neurology and Neuroscience Center, The First Hospital of Jilin University, Jilin University, Changchun, China; Cognitive Center, Department of Neurology, The First Hospital of Jilin University, Jilin University, Changchun, China
| | - Cui Xinran
- Department of Neurology and Neuroscience Center, The First Hospital of Jilin University, Jilin University, Changchun, China; Cognitive Center, Department of Neurology, The First Hospital of Jilin University, Jilin University, Changchun, China
| | - Xu Yanjiao
- Department of Neurology and Neuroscience Center, The First Hospital of Jilin University, Jilin University, Changchun, China; Cognitive Center, Department of Neurology, The First Hospital of Jilin University, Jilin University, Changchun, China
| | - Sun Li
- Department of Neurology and Neuroscience Center, The First Hospital of Jilin University, Jilin University, Changchun, China; Cognitive Center, Department of Neurology, The First Hospital of Jilin University, Jilin University, Changchun, China.
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Deshmukh H, Santos JM, Bender M, Dufour JM, Lovett J, Shen CL. Peanut Shell Extract Improves Mitochondrial Function in db/db Mice via Suppression of Oxidative Stress and Inflammation. Nutrients 2024; 16:1977. [PMID: 38999726 PMCID: PMC11243022 DOI: 10.3390/nu16131977] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Revised: 06/12/2024] [Accepted: 06/17/2024] [Indexed: 07/14/2024] Open
Abstract
Accumulating evidence shows a strong correlation between type 2 diabetes mellitus, mitochondrial dysfunction, and oxidative stress. We evaluated the effects of dietary peanut shell extract (PSE) supplementation on mitochondrial function and antioxidative stress/inflammation markers in diabetic mice. Fourteen db/db mice were randomly assigned to a diabetic group (DM in AIN-93G diet) and a PSE group (1% wt/wt PSE in AIN-93G diet) for 5 weeks. Six C57BL/6J mice were fed with an AIN-93G diet for 5 weeks (control group). Gene and protein expression in the liver, brain, and white adipose tissue (WAT) were determined using qRT-PCR and Immunoblot, respectively. Compared to the control group, the DM group had (i) increased gene and protein expression levels of DRP1 (fission), PINK1 (mitophagy), and TNFα (inflammation) and (ii) decreased gene and protein expression levels of MFN1, MFN2, OPA1 (fusion), TFAM, PGC-1α (biogenesis), NRF2 (antioxidative stress) and IBA1 (microglial activation) in the liver, brain, and WAT of db/db mice. Supplementation of PSE into the diet restored the DM-induced changes in the gene and protein expression of DRP1, PINK1, TNFα, MFN1, MFN2, OPA1, TFAM, PGC-1α, NRF2, and IBA1 in the liver, brain, and WAT of db/db mice. This study demonstrates that PSE supplementation improved mitochondrial function in the brain, liver, and WAT of db/db mice, in part due to suppression of oxidative stress and inflammation.
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Affiliation(s)
- Hemalata Deshmukh
- Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; (H.D.); (J.M.S.); (J.L.)
| | - Julianna M. Santos
- Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; (H.D.); (J.M.S.); (J.L.)
| | - Matthew Bender
- Department of Medical Education, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; (M.B.); (J.M.D.)
| | - Jannette M. Dufour
- Department of Medical Education, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; (M.B.); (J.M.D.)
- Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
- Center of Excellence for Integrative Health, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
- Obesity Research Institute, Texas Tech University, Lubbock, TX 79401, USA
| | - Jacob Lovett
- Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; (H.D.); (J.M.S.); (J.L.)
| | - Chwan-Li Shen
- Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; (H.D.); (J.M.S.); (J.L.)
- Center of Excellence for Integrative Health, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
- Obesity Research Institute, Texas Tech University, Lubbock, TX 79401, USA
- Center of Excellence for Translational Neuroscience and Therapeutics, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
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15
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Chen B, Schneeberger M. Neuro-Adipokine Crosstalk in Alzheimer's Disease. Int J Mol Sci 2024; 25:5932. [PMID: 38892118 PMCID: PMC11173274 DOI: 10.3390/ijms25115932] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2024] [Revised: 05/24/2024] [Accepted: 05/27/2024] [Indexed: 06/21/2024] Open
Abstract
The connection between body weight alterations and Alzheimer's disease highlights the intricate relationship between the brain and adipose tissue in the context of neurological disorders. During midlife, weight gain increases the risk of cognitive decline and dementia, whereas in late life, weight gain becomes a protective factor. Despite their substantial impact on metabolism, the role of adipokines in the transition from healthy aging to neurological disorders remains largely unexplored. We aim to investigate how the adipose tissue milieu and the secreted adipokines are involved in the transition between biological and pathological aging, highlighting the bidirectional relationship between the brain and systemic metabolism. Understanding the function of these adipokines will allow us to identify biomarkers for early detection of Alzheimer's disease and uncover novel therapeutic options.
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Affiliation(s)
- Bandy Chen
- Laboratory of Neurovascular Control of Homeostasis, Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, CT 06510, USA;
| | - Marc Schneeberger
- Laboratory of Neurovascular Control of Homeostasis, Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, CT 06510, USA;
- Wu Tsai Institute for Mind and Brain, Yale University, New Haven, CT 06510, USA
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16
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Biazus Soares G, Mahmoud O, Yosipovitch G, Mochizuki H. The mind-skin connection: A narrative review exploring the link between inflammatory skin diseases and psychological stress. J Eur Acad Dermatol Venereol 2024; 38:821-834. [PMID: 38311707 DOI: 10.1111/jdv.19813] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Accepted: 11/16/2023] [Indexed: 02/06/2024]
Abstract
Inflammatory skin diseases are known to negatively impact patient psychology, with individuals experiencing higher rates of stress and subsequent diminished quality of life, as well as mental health issues including anxiety and depression. Moreover, increased psychological stress has been found to exacerbate existing inflammatory skin diseases. The association between inflammatory skin diseases and psychological stress is a timely topic, and a framework to better understand the relationship between the two that integrates available literature is needed. In this narrative review article, we discuss potential neurobiological mechanisms behind psychological stress due to inflammatory skin diseases, focusing mainly on proinflammatory cytokines in the circulating system (the brain-gut-skin communications) and the default mode network in the brain. We also discuss potential descending pathways from the brain that lead to aggravation of inflammatory skin diseases due to psychological stress, including the central and peripheral hypothalamic-pituitary-adrenal axes, peripheral nerves and the skin barrier function.
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Affiliation(s)
- G Biazus Soares
- Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, Miami Itch Center, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - O Mahmoud
- Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, Miami Itch Center, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - G Yosipovitch
- Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, Miami Itch Center, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - H Mochizuki
- Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, Miami Itch Center, University of Miami Miller School of Medicine, Miami, Florida, USA
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Chen Q, Sun T, He Q, Yu J, Zhang X, Han L, Ren Y. Study of decreased serum levels of C1q/TNF-related protein 4 (CTRP4) in major depressive disorder. J Psychiatr Res 2024; 172:274-280. [PMID: 38417323 DOI: 10.1016/j.jpsychires.2024.01.046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Revised: 01/19/2024] [Accepted: 01/22/2024] [Indexed: 03/01/2024]
Abstract
BACKGROUND The adipokines secreted by adipocytes might play an important role through crossing the blood brain barrier to the brain, which could mediate the common physiological pathway between depression and obesity. CTRP4, a member of the CTRP family, is highly expressed in human adipose tissue and brain tissue. OBJECTIVE this study aimed to measure serum C1q/TNF-related protein 4 (CTRP4) levels in depressive patients to explore the association between CTRP4 levels and depression. METHODS depressive patients (n = 138), healthy controls (n = 100) were enrolled from September 2020 to December 2021. The level of serum CTRP4 was measured by enzymes linked to immunosorbent assay (ELISA). Other biochemical indicators were measured by Advia 2400 automatic biochemistry analyzer. Depressive symptoms of patients were assessed using the Hamilton Depression Scale-24 item (HAMD-24). RESULTS this study found that serum CTRP4 levels in the MDD group were lower than that of the health control (P < 0.001). Serum CTRP4 levels were negatively correlated with HAMD-24 scores (r = -0.368; P = 0.001). The serum CTRP4 levels were negatively correlated with Total Cholesterol (TC), Triglyceride (TG) and Low-Density Lipoprotein Cholesterol (LDL-C), but were positively associated with high density lipid-cholesterol (HDL-C) (r = -0.267, r = -0.255, r = -0.312 and r = 0.280; P = 0.017, P = 0.023, P = 0.005 and P = 0.012). The ROC curve of CTRP4 showed that the Area Under Curve (AUC) was 0.856, P < 0.001. CONCLUSION the serum CTRP4 levels in MDD patients were lower than that in health control, which might mediate the physiological progress of MDD patients.
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Affiliation(s)
- Qian Chen
- Department of Clinical Laboratory, Wuhan Pulmonary Hospital, Baofeng Road, Qiaokou District, Wuhan, 430030, China.
| | - Ting Sun
- Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Zhangzhidong Road, Wuhan, 430000, China
| | - Qian He
- Department of Clinical Laboratory, Wuhan Pulmonary Hospital, Baofeng Road, Qiaokou District, Wuhan, 430030, China.
| | - Jian Yu
- Department of Clinical Laboratory, Wuhan Pulmonary Hospital, Baofeng Road, Qiaokou District, Wuhan, 430030, China.
| | - Xuechao Zhang
- Department of Clinical Laboratory, Wuhan Pulmonary Hospital, Baofeng Road, Qiaokou District, Wuhan, 430030, China.
| | - Lu Han
- Department of Clinical Laboratory, Wuhan Blood Center, Baofeng Road, Qiaokou District, Wuhan, 430030, China.
| | - Yi Ren
- Department of Clinical Laboratory, Wuhan Pulmonary Hospital, Baofeng Road, Qiaokou District, Wuhan, 430030, China.
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18
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Małujło-Balcerska E, Pietras T. Adipocytokines levels as potential biomarkers for discriminating patients with a diagnosis of depressive disorder from healthy controls. J Psychiatr Res 2024; 171:163-170. [PMID: 38290234 DOI: 10.1016/j.jpsychires.2024.01.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Revised: 01/04/2024] [Accepted: 01/15/2024] [Indexed: 02/01/2024]
Abstract
BACKGROUND Depressive disorder is a complex mental health condition in which the etiopathogenesis involves several factors. Suitable biomarkers for the development of depression have not yet been established. Alterations in cytokines are assumed to be involved in the pathophysiology of depressive disorder. Adipokines (also known as adipocytokines) are important factors that not only regulate the energy balance but also regulate the inflammatory and immune responses. This study investigated the serum levels of adiponectin, leptin, resistin, chemerin, and fetuin A and the possible role of these adipokines in depressive disorder. METHODS We recruited a total of 73 patients diagnosed with recurrent depressive disorder (rDD) and 54 age- and sex-matched healthy controls (HCs). Serum adipocytokines were determined using ELISA kits (R&D, USA). The serum levels of the investigated molecules between depressive patients and HCs were compared, and diagnostic values were evaluated using the receiver operating characteristic (ROC) curve method for discriminating depressive patients from HCs. Correlations between the molecules and clinical variables were also evaluated. RESULTS Patients with rDD had lower levels of serum adiponectin and chemerin and higher levels of serum leptin, resistin and fetuin A (p < 0.05) vs. controls. Moreover, ROC curve analysis showed that the area under the curve (AUC) values of above set of adipocytkines were >0.7, with a sensitivity and specificity over 80% in discriminating patients with rDD from HCs. CONCLUSIONS These results suggest that circulating adipocytokies may hold promise as biomarkers for the diagnosis of rDD.
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Affiliation(s)
| | - Tadeusz Pietras
- Department of Clinical Pharmacology, Medical University of Łódź, Poland; Second Department of Psychiatry, Institute of Psychiatry and Neurology, Warsaw, Poland
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Bettinetti-Luque M, Trujillo-Estrada L, Garcia-Fuentes E, Andreo-Lopez J, Sanchez-Varo R, Garrido-Sánchez L, Gómez-Mediavilla Á, López MG, Garcia-Caballero M, Gutierrez A, Baglietto-Vargas D. Adipose tissue as a therapeutic target for vascular damage in Alzheimer's disease. Br J Pharmacol 2024; 181:840-878. [PMID: 37706346 DOI: 10.1111/bph.16243] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Revised: 08/11/2023] [Accepted: 09/01/2023] [Indexed: 09/15/2023] Open
Abstract
Adipose tissue has recently been recognized as an important endocrine organ that plays a crucial role in energy metabolism and in the immune response in many metabolic tissues. With this regard, emerging evidence indicates that an important crosstalk exists between the adipose tissue and the brain. However, the contribution of adipose tissue to the development of age-related diseases, including Alzheimer's disease, remains poorly defined. New studies suggest that the adipose tissue modulates brain function through a range of endogenous biologically active factors known as adipokines, which can cross the blood-brain barrier to reach the target areas in the brain or to regulate the function of the blood-brain barrier. In this review, we discuss the effects of several adipokines on the physiology of the blood-brain barrier, their contribution to the development of Alzheimer's disease and their therapeutic potential. LINKED ARTICLES: This article is part of a themed issue From Alzheimer's Disease to Vascular Dementia: Different Roads Leading to Cognitive Decline. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.6/issuetoc.
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Affiliation(s)
- Miriam Bettinetti-Luque
- Departamento de Biología Celular, Genética y Fisiología, Instituto de Investigación Biomédica de Málaga (IBIMA)-Plataforma BIONAND, Facultad de Ciencias, Universidad de Málaga, Málaga, Spain
| | - Laura Trujillo-Estrada
- Departamento de Biología Celular, Genética y Fisiología, Instituto de Investigación Biomédica de Málaga (IBIMA)-Plataforma BIONAND, Facultad de Ciencias, Universidad de Málaga, Málaga, Spain
- CIBER de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain
| | - Eduardo Garcia-Fuentes
- Unidad de Gestión Clínica Aparato Digestivo, Hospital Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga (IBIMA)-Plataforma BIONAND, Málaga, Spain
- CIBER de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain
| | - Juana Andreo-Lopez
- Departamento de Biología Celular, Genética y Fisiología, Instituto de Investigación Biomédica de Málaga (IBIMA)-Plataforma BIONAND, Facultad de Ciencias, Universidad de Málaga, Málaga, Spain
| | - Raquel Sanchez-Varo
- Departamento de Biología Celular, Genética y Fisiología, Instituto de Investigación Biomédica de Málaga (IBIMA)-Plataforma BIONAND, Facultad de Ciencias, Universidad de Málaga, Málaga, Spain
- CIBER de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain
- Departamento de Fisiología Humana, Histología Humana, Anatomía Patológica y Educación Física y Deportiva, Facultad de Medicina, Universidad de Málaga, Málaga, Spain
| | - Lourdes Garrido-Sánchez
- CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
- Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga (IBIMA)-Plataforma BIONAND, Málaga, Spain
| | - Ángela Gómez-Mediavilla
- Departamento de Farmacología, Facultad de Medicina. Instituto Teófilo Hernando para la I+D de Fármacos, Universidad Autónoma de Madrid, Madrid, Spain
| | - Manuela G López
- Departamento de Farmacología, Facultad de Medicina. Instituto Teófilo Hernando para la I+D de Fármacos, Universidad Autónoma de Madrid, Madrid, Spain
- Instituto de Investigaciones Sanitarias (IIS-IP), Hospital Universitario de la Princesa, Madrid, Spain
| | - Melissa Garcia-Caballero
- Departamento de Biología Molecular y Bioquímica, Instituto de Investigación Biomédica de Málaga (IBIMA)-Plataforma BIONAND, Facultad de Ciencias, Universidad de Málaga, Málaga, Spain
| | - Antonia Gutierrez
- Departamento de Biología Celular, Genética y Fisiología, Instituto de Investigación Biomédica de Málaga (IBIMA)-Plataforma BIONAND, Facultad de Ciencias, Universidad de Málaga, Málaga, Spain
- CIBER de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain
| | - David Baglietto-Vargas
- Departamento de Biología Celular, Genética y Fisiología, Instituto de Investigación Biomédica de Málaga (IBIMA)-Plataforma BIONAND, Facultad de Ciencias, Universidad de Málaga, Málaga, Spain
- CIBER de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain
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Milanowski J, Nuszkiewicz J, Lisewska B, Lisewski P, Szewczyk-Golec K. Adipokines, Vitamin D, and Selected Inflammatory Biomarkers among Parkinson's Disease Patients with and without Dyskinesia: A Preliminary Examination. Metabolites 2024; 14:106. [PMID: 38392998 PMCID: PMC10890066 DOI: 10.3390/metabo14020106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Revised: 02/01/2024] [Accepted: 02/02/2024] [Indexed: 02/25/2024] Open
Abstract
Parkinson's disease (PD), a widely recognized neurodegenerative disorder, is characterized by a spectrum of symptoms including motor fluctuations and dyskinesia. Neuroinflammation and dysregulation of adipokines are increasingly implicated in the progression of PD. This preliminary study investigated the levels of inflammatory biomarkers and adipokines, namely interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), C-reactive protein (CRP), visfatin, progranulin, and 25(OH)-vitamin D in 52 PD patients, divided equally between those with and without dyskinesia and 26 healthy controls. Significant differences in the levels of IL-6, TNF-α, visfatin, and progranulin were noted between the groups. Patients with dyskinesia exhibited notably higher IL-6 levels compared to controls, and TNF-α was significantly elevated in both PD patient groups relative to the control group. Additionally, visfatin levels were higher in PD patients without dyskinesia as opposed to those with dyskinesia, and progranulin levels were elevated in the non-dyskinetic PD group compared to controls. The findings highlight the potential role of the examined biomarkers in the pathophysiology of PD. Changes in levels of the tested inflammatory biomarkers and adipokines might be associated with Parkinson's disease and its symptoms such as dyskinesia.
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Affiliation(s)
- Jan Milanowski
- Student Research Club of Medical Biology and Biochemistry, Department of Medical Biology and Biochemistry, Faculty of Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 24 Karłowicza St., 85-092 Bydgoszcz, Poland
| | - Jarosław Nuszkiewicz
- Department of Medical Biology and Biochemistry, Faculty of Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 24 Karłowicza St., 85-092 Bydgoszcz, Poland
| | - Beata Lisewska
- Medical Center "Neuromed", 14 Jana Biziela St., 85-163 Bydgoszcz, Poland
| | - Paweł Lisewski
- Medical Center "Neuromed", 14 Jana Biziela St., 85-163 Bydgoszcz, Poland
| | - Karolina Szewczyk-Golec
- Department of Medical Biology and Biochemistry, Faculty of Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 24 Karłowicza St., 85-092 Bydgoszcz, Poland
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21
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Wang J, Sun L, You J, Peng H, Yan H, Wang J, Sun F, Cui M, Wang S, Zhang Z, Fan X, Liu D, Liu C, Qiu C, Chen C, Xu Z, Chen J, Li W, Liu B. Role and mechanism of PVN-sympathetic-adipose circuit in depression and insulin resistance induced by chronic stress. EMBO Rep 2023; 24:e57176. [PMID: 37870400 DOI: 10.15252/embr.202357176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 09/29/2023] [Accepted: 10/09/2023] [Indexed: 10/24/2023] Open
Abstract
Chronic stress induces depression and insulin resistance, between which there is a bidirectional relationship. However, the mechanisms underlying this comorbidity remain unclear. White adipose tissue (WAT), innervated by sympathetic nerves, serves as a central node in the interorgan crosstalk through adipokines. Abnormal secretion of adipokines is involved in mood disorders and metabolic morbidities. We describe here a brain-sympathetic nerve-adipose circuit originating in the hypothalamic paraventricular nucleus (PVN) with a role in depression and insulin resistance induced by chronic stress. PVN neurons are labelled after inoculation of pseudorabies virus (PRV) into WAT and are activated under restraint stress. Chemogenetic manipulations suggest a role for the PVN in depression and insulin resistance. Chronic stress increases the sympathetic innervation of WAT and downregulates several antidepressant and insulin-sensitizing adipokines, including leptin, adiponectin, Angptl4 and Sfrp5. Chronic activation of the PVN has similar effects. β-adrenergic receptors translate sympathetic tone into an adipose response, inducing downregulation of those adipokines and depressive-like behaviours and insulin resistance. We finally show that AP-1 has a role in the regulation of adipokine expression under chronic stress.
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Affiliation(s)
- Jing Wang
- Department of Rehabilitation, Binzhou Medical University Hospital, Binzhou, China
- Department of Neurology, Binzhou Medical University Hospital, Binzhou, China
- Medical Research Center, Binzhou Medical University Hospital, Binzhou, China
| | - Linshan Sun
- Department of Neurology, Binzhou Medical University Hospital, Binzhou, China
| | - Jingjing You
- Department of Rehabilitation, Binzhou Medical University Hospital, Binzhou, China
- Department of Neurology, Binzhou Medical University Hospital, Binzhou, China
- Medical Research Center, Binzhou Medical University Hospital, Binzhou, China
| | - Honghai Peng
- Department of Neurosurgery, Central Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Haijing Yan
- Medical Research Center, Binzhou Medical University Hospital, Binzhou, China
- Department of Pharmacology, College of Basic Medicine, Binzhou Medical University, Yantai, China
| | - Jiangong Wang
- Department of Rehabilitation, Binzhou Medical University Hospital, Binzhou, China
- Department of Neurology, Binzhou Medical University Hospital, Binzhou, China
- Medical Research Center, Binzhou Medical University Hospital, Binzhou, China
| | - Fengjiao Sun
- Department of Rehabilitation, Binzhou Medical University Hospital, Binzhou, China
- Department of Neurology, Binzhou Medical University Hospital, Binzhou, China
- Medical Research Center, Binzhou Medical University Hospital, Binzhou, China
| | - Minghu Cui
- Department of Psychiatry, Binzhou Medical University Hospital, Binzhou, China
| | - Sanwang Wang
- Department of Psychiatry, Binzhou Medical University Hospital, Binzhou, China
| | - Zheng Zhang
- Department of Psychiatry, Binzhou Youfu Hospital, Binzhou, China
| | - Xueli Fan
- Department of Neurology, Binzhou Medical University Hospital, Binzhou, China
| | - Dunjiang Liu
- Medical Research Center, Binzhou Medical University Hospital, Binzhou, China
| | - Cuilan Liu
- Medical Research Center, Binzhou Medical University Hospital, Binzhou, China
| | - Changyun Qiu
- Medical Research Center, Binzhou Medical University Hospital, Binzhou, China
| | - Chao Chen
- Department of Neurology, Binzhou Medical University Hospital, Binzhou, China
| | - Zhicheng Xu
- Medical Research Center, Binzhou Medical University Hospital, Binzhou, China
| | - Jinbo Chen
- Department of Neurology, Binzhou Medical University Hospital, Binzhou, China
| | - Wei Li
- Department of Rehabilitation, Binzhou Medical University Hospital, Binzhou, China
| | - Bin Liu
- Department of Rehabilitation, Binzhou Medical University Hospital, Binzhou, China
- Department of Neurology, Binzhou Medical University Hospital, Binzhou, China
- Medical Research Center, Binzhou Medical University Hospital, Binzhou, China
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22
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Leung WKC, Yau SY, Suen LKP, Lam SC. Effect of exercise interventions on brain-derived neurotrophic factor expression in people with overweight and obesity: protocol for a systematic review and meta-analysis. BMJ Open 2023; 13:e076118. [PMID: 37865417 PMCID: PMC10603475 DOI: 10.1136/bmjopen-2023-076118] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Accepted: 09/27/2023] [Indexed: 10/23/2023] Open
Abstract
INTRODUCTION Epidemic obesity ('globobesity') has led to a considerable rise in the prevalence and incidence of many disabling conditions, including cognitive dysfunction. Recent evidence has suggested that habitual exercise can alleviate the deleterious effects of obesity on cognitive functioning across the lifespan. Given that there is a potential link among obesity, exercise, cognitive health and brain-derived neurotrophic factor (BDNF), this systematic review aims to critically appraise interventional trials on exercise and BDNF and to estimate the pooled effect of exercise training on BDNF levels among healthy individuals with overweight and obesity. METHODS AND ANALYSIS Six electronic databases-PubMed, MEDLINE, EMBASE, Web of Science, Ovid Nursing Database and SPORTDiscus-will be searched from their inception through December 2022. Only interventional studies, including randomised controlled trials and quasi-experimental studies, with full text available and reported in English will be included. The primary outcomes will be changes in BDNF levels among healthy subjects with overweight and obesity following either acute or chronic bouts of exercise interventions. Two reviewers will independently conduct data extraction and risk of bias assessment for included trials using the Physiotherapy Evidence Database Scale. We will produce a narrative synthesis, with findings categorised by sex, age groups and types of exercise training. Data will be extracted and pooled for meta-analyses using random-effects models. ETHICS AND DISSEMINATION No formal ethical approval is required for this systematic review. The findings of this review will be disseminated through peer-reviewed publications. PROSPERO REGISTRATION NUMBER CRD42023414868.
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Affiliation(s)
| | - Suk Yu Yau
- Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hong Kong SAR, China
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Huber K, Szerenos E, Lewandowski D, Toczylowski K, Sulik A. The Role of Adipokines in the Pathologies of the Central Nervous System. Int J Mol Sci 2023; 24:14684. [PMID: 37834128 PMCID: PMC10572192 DOI: 10.3390/ijms241914684] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Revised: 09/24/2023] [Accepted: 09/27/2023] [Indexed: 10/15/2023] Open
Abstract
Adipokines are protein hormones secreted by adipose tissue in response to disruptions in physiological homeostasis within the body's systems. The regulatory functions of adipokines within the central nervous system (CNS) are multifaceted and intricate, and they have been identified in a number of pathologies. Therefore, specific adipokines have the potential to be used as biomarkers for screening purposes in neurological dysfunctions. The systematic review presented herein focuses on the analysis of the functions of various adipokines in the pathogenesis of CNS diseases. Thirteen proteins were selected for analysis through scientific databases. It was found that these proteins can be identified within the cerebrospinal fluid either by their ability to modify their molecular complex and cross the blood-brain barrier or by being endogenously produced within the CNS itself. As a result, this can correlate with their measurability during pathological processes, including Alzheimer's disease, amyotrophic lateral sclerosis, multiple sclerosis, depression, or brain tumors.
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Affiliation(s)
| | | | | | - Kacper Toczylowski
- Department of Pediatric Infectious Diseases, Medical University of Bialystok, Waszyngtona 17, 15-274 Bialystok, Poland
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24
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Rodolaki K, Pergialiotis V, Iakovidou N, Boutsikou T, Iliodromiti Z, Kanaka-Gantenbein C. The impact of maternal diabetes on the future health and neurodevelopment of the offspring: a review of the evidence. Front Endocrinol (Lausanne) 2023; 14:1125628. [PMID: 37469977 PMCID: PMC10352101 DOI: 10.3389/fendo.2023.1125628] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Accepted: 06/12/2023] [Indexed: 07/21/2023] Open
Abstract
Maternal health during gestational period is undoubtedly critical in shaping optimal fetal development and future health of the offspring. Gestational diabetes mellitus is a metabolic disorder occurring in pregnancy with an alarming increasing incidence worldwide during recent years. Over the years, there is a growing body of evidence that uncontrolled maternal hyperglycaemia during pregnancy can potentially have detrimental effect on the neurodevelopment of the offspring. Both human and animal data have linked maternal diabetes with motor and cognitive impairment, as well as autism spectrum disorders, attention deficit hyperactivity disorder, learning abilities and psychiatric disorders. This review presents the available data from current literature investigating the relationship between maternal diabetes and offspring neurodevelopmental impairment. Moreover, possible mechanisms accounting for the detrimental effects of maternal diabetes on fetal brain like fetal neuroinflammation, iron deficiency, epigenetic alterations, disordered lipid metabolism and structural brain abnormalities are also highlighted. On the basis of the evidence demonstrated in the literature, it is mandatory that hyperglycaemia during pregnancy will be optimally controlled and the impact of maternal diabetes on offspring neurodevelopment will be more thoroughly investigated.
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Affiliation(s)
- Kalliopi Rodolaki
- First Department of Pediatrics, “Aghia Sophia” Children’s Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Vasilios Pergialiotis
- First Department of Obstetrics and Gynecology, Alexandra Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Nikoleta Iakovidou
- Neonatal Department, Aretaieio Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Theodora Boutsikou
- Neonatal Department, Aretaieio Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Zoe Iliodromiti
- Neonatal Department, Aretaieio Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Christina Kanaka-Gantenbein
- First Department of Pediatrics, “Aghia Sophia” Children’s Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
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25
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Fu X, Wang Y, Zhao F, Cui R, Xie W, Liu Q, Yang W. Shared biological mechanisms of depression and obesity: focus on adipokines and lipokines. Aging (Albany NY) 2023; 15:5917-5950. [PMID: 37387537 PMCID: PMC10333059 DOI: 10.18632/aging.204847] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Accepted: 06/01/2023] [Indexed: 07/01/2023]
Abstract
Depression and obesity are both common disorders currently affecting public health, frequently occurring simultaneously within individuals, and the relationship between these disorders is bidirectional. The association between obesity and depression is highly co-morbid and tends to significantly exacerbate metabolic and related depressive symptoms. However, the neural mechanism under the mutual control of obesity and depression is largely inscrutable. This review focuses particularly on alterations in systems that may mechanistically explain the in vivo homeostatic regulation of the obesity and depression link, such as immune-inflammatory activation, gut microbiota, neuroplasticity, HPA axis dysregulation as well as neuroendocrine regulators of energy metabolism including adipocytokines and lipokines. In addition, the review summarizes potential and future treatments for obesity and depression and raises several questions that need to be answered in future research. This review will provide a comprehensive description and localization of the biological connection between obesity and depression to better understand the co-morbidity of obesity and depression.
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Affiliation(s)
- Xiying Fu
- Department of Endocrinology, The Second Hospital of Jilin University, Changchun 130041, P.R. China
- Jilin Provincial Key Laboratory for Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun 130041, P.R. China
| | - Yicun Wang
- Jilin Provincial Key Laboratory for Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun 130041, P.R. China
| | - Fangyi Zhao
- Jilin Provincial Key Laboratory for Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun 130041, P.R. China
| | - Ranji Cui
- Jilin Provincial Key Laboratory for Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun 130041, P.R. China
| | - Wei Xie
- Jilin Provincial Key Laboratory for Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun 130041, P.R. China
| | - Qianqian Liu
- Jilin Provincial Key Laboratory for Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun 130041, P.R. China
| | - Wei Yang
- Jilin Provincial Key Laboratory for Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun 130041, P.R. China
- Department of Neurology, The Second Hospital of Jilin University, Changchun 130041, P.R. China
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26
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Würfel M, Blüher M, Stumvoll M, Ebert T, Kovacs P, Tönjes A, Breitfeld J. Adipokines as Clinically Relevant Therapeutic Targets in Obesity. Biomedicines 2023; 11:biomedicines11051427. [PMID: 37239098 DOI: 10.3390/biomedicines11051427] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Revised: 05/04/2023] [Accepted: 05/08/2023] [Indexed: 05/28/2023] Open
Abstract
Adipokines provide an outstanding role in the comprehensive etiology of obesity and may link adipose tissue dysfunction to further metabolic and cardiovascular complications. Although several adipokines have been identified in terms of their physiological roles, many regulatory circuits remain unclear and translation from experimental studies to clinical applications has yet to occur. Nevertheless, due to their complex metabolic properties, adipokines offer immense potential for their use both as obesity-associated biomarkers and as relevant treatment strategies for overweight, obesity and metabolic comorbidities. To provide an overview of the current clinical use of adipokines, this review summarizes clinical studies investigating the potential of various adipokines with respect to diagnostic and therapeutic treatment strategies for obesity and linked metabolic disorders. Furthermore, an overview of adipokines, for which a potential for clinical use has been demonstrated in experimental studies to date, will be presented. In particular, promising data revealed that fibroblast growth factor (FGF)-19, FGF-21 and leptin offer great potential for future clinical application in the treatment of obesity and related comorbidities. Based on data from animal studies or other clinical applications in addition to obesity, adipokines including adiponectin, vaspin, resistin, chemerin, visfatin, bone morphogenetic protein 7 (BMP-7) and tumor necrosis factor alpha (TNF-α) provide potential for human clinical application.
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Affiliation(s)
- Marleen Würfel
- Department of Medicine III, Division of Endocrinology, Nephrology and Rheumatology, University of Leipzig, Liebigstr. 18, 04103 Leipzig, Germany
| | - Matthias Blüher
- Department of Medicine III, Division of Endocrinology, Nephrology and Rheumatology, University of Leipzig, Liebigstr. 18, 04103 Leipzig, Germany
- Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG), Helmholtz Center Munich at the University of Leipzig and the University of Leipzig Medical Center, 04103 Leipzig, Germany
| | - Michael Stumvoll
- Department of Medicine III, Division of Endocrinology, Nephrology and Rheumatology, University of Leipzig, Liebigstr. 18, 04103 Leipzig, Germany
| | - Thomas Ebert
- Department of Medicine III, Division of Endocrinology, Nephrology and Rheumatology, University of Leipzig, Liebigstr. 18, 04103 Leipzig, Germany
| | - Peter Kovacs
- Department of Medicine III, Division of Endocrinology, Nephrology and Rheumatology, University of Leipzig, Liebigstr. 18, 04103 Leipzig, Germany
- German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany
| | - Anke Tönjes
- Department of Medicine III, Division of Endocrinology, Nephrology and Rheumatology, University of Leipzig, Liebigstr. 18, 04103 Leipzig, Germany
| | - Jana Breitfeld
- Department of Medicine III, Division of Endocrinology, Nephrology and Rheumatology, University of Leipzig, Liebigstr. 18, 04103 Leipzig, Germany
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Hegazy HA, Abo-ElMatty DM, Farid O, Saleh S, Ghattas MH, Omar NN. Nano-melatonin and-histidine modulate adipokines and neurotransmitters to improve cognition in HFD-fed rats: A formula to study. Biochimie 2023; 207:137-152. [PMID: 36351496 DOI: 10.1016/j.biochi.2022.11.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Revised: 10/01/2022] [Accepted: 11/02/2022] [Indexed: 11/08/2022]
Abstract
The established correlation between obesity and cognitive impairment portrays pharmacological products aimed at both disorders as an important therapeutic advance. Modulation of dysregulated adipokines and neurotransmitters is hence a critical aspect of the assessment of in-use drugs. At the cellular level, repairments in brain barrier integrity and cognitive flexibility are the main checkpoints. The aim of this study was to investigate whether melatonin and histidine, alone or in combination, could produce weight loss, meanwhile improve the cognitive processes. In this study, obese rat model was established by feeding high fat diet (HFD) composed of 25% fats (soybean oil) for 8 weeks, accompanied by melatonin (10 mg/kg), histidine (780 mg/kg), and combination of both in conventional form and nanoform. At the end of the study, adiposity hormones, neuronal monoamines and amino acids, brain derived neurotrophic factor (BDNF) and zonula occluden-1 (ZO-1) were assessed. HFD feeding resulted in significant weight gain and poor performance on cognitive test. Coadministration of histidine in the nanoform increased the level of ZO-1; an indicator of improving the brain barrier integrity, along with adjusting the adipokines and neurotransmitters levels, which had a positive impact on learning tasks. Cotreatment with melatonin resulted in an increase in the level of BDNF, marking ameliorated synaptic anomalies and learning disabilities, while reducing weight gain. On the other hand, the combination of melatonin and histidine reinstated the synaptic plasticity as well as brain barrier junctions, as demonstrated by increased levels of BDNF and ZO-1, positively affecting weight loss and the intellectual function.
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Affiliation(s)
- Heba Ahmed Hegazy
- Department of Biochemistry, Faculty of Pharmacy, Modern University for Technology and Information, Cairo, Egypt.
| | - Dina M Abo-ElMatty
- Department of Biochemistry, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt.
| | - Omar Farid
- Department of Physiology, National Organization for Drug Control & Research, Giza, Egypt.
| | - Sami Saleh
- Department of Biochemistry, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt.
| | - Maivel H Ghattas
- Department of Medical Biochemistry, Faculty of Medicine, Port Said University, Port Said, Egypt.
| | - Nesreen Nabil Omar
- Department of Biochemistry, Faculty of Pharmacy, Modern University for Technology and Information, Cairo, Egypt.
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Skórzyńska-Dziduszko KE, Makarewicz A, Błażewicz A. Peripubertal Alterations of Leptin Levels in Patients with Autism Spectrum Disorder and Elevated or Normal Body Weight. Int J Mol Sci 2023; 24:ijms24054878. [PMID: 36902307 PMCID: PMC10003704 DOI: 10.3390/ijms24054878] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Revised: 02/24/2023] [Accepted: 02/28/2023] [Indexed: 03/06/2023] Open
Abstract
Leptin, which plays a key role in energy homeostasis, is known as a neurotrophic factor possibly linking nutrition and neurodevelopment. Available data on the association between leptin and autism spectrum disorder (ASD) are confusing. The aim of this study was to explore whether plasma levels of leptin in pre- and post-pubertal children with ASD and/or overweightness/obesity differ from those of BMI- and age-matched healthy controls. Leptin levels were determined in 287 pre-pubertal children (mean age 8.09 years), classified as follows: ASD with overweightness/obesity (ASD+/Ob+); ASD without overweightness/obesity (ASD+/Ob-); non-ASD with overweightness/obesity (ASD-/Ob+); non-ASD without overweightness/obesity (ASD-/Ob-). The assessment was repeated in 258 of the children post-pubertally (mean age 14.26 years). There were no significant differences in leptin levels either before or after puberty between ASD+/Ob+ and ASD-/Ob+ or between ASD+/Ob- and ASD-/Ob-, although there was a strong trend toward significance for higher pre-pubertal leptin levels in ASD+/Ob- than in ASD-/Ob-. Post-pubertal leptin levels were significantly lower than pre-pubertal levels in ASD+/Ob+, ASD-/Ob+, and ASD+/Ob- and higher in ASD-/Ob-. Leptin levels, elevated pre-pubertally in the children with overweightness/obesity as well as in children with ASD and normal BMI, decrease with age, in contrast to the increasing leptin levels in healthy controls.
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Affiliation(s)
| | - Agata Makarewicz
- Department of Psychiatry, Psychotherapy and Early Intervention, Medical University of Lublin, 20-439 Lublin, Poland
| | - Anna Błażewicz
- Department of Pathobiochemistry and Interdisciplinary Applications of Ion Chromatography, Medical University of Lublin, 1 Chodźki Street, 20-093 Lublin, Poland
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29
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Kuckuck S, van der Valk ES, Scheurink AJW, van der Voorn B, Iyer AM, Visser JA, Delhanty PJD, van den Berg SAA, van Rossum EFC. Glucocorticoids, stress and eating: The mediating role of appetite-regulating hormones. Obes Rev 2023; 24:e13539. [PMID: 36480471 PMCID: PMC10077914 DOI: 10.1111/obr.13539] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Revised: 11/07/2022] [Accepted: 11/15/2022] [Indexed: 12/13/2022]
Abstract
Disrupted hormonal appetite signaling plays a crucial role in obesity as it may lead to uncontrolled reward-related eating. Such disturbances can be induced not only by weight gain itself but also by glucocorticoid overexposure, for example, due to chronic stress, disease, or medication use. However, the exact pathways are just starting to be understood. Here, we present a conceptual framework of how glucocorticoid excess may impair hormonal appetite signaling and, consequently, eating control in the context of obesity. The evidence we present suggests that counteracting glucocorticoid excess can lead to improvements in appetite signaling and may therefore pose a crucial target for obesity prevention and treatment. In turn, targeting hormonal appetite signals may not only improve weight management and eating behavior but may also decrease detrimental effects of glucocorticoid excess on cardio-metabolic outcomes and mood. We conclude that gaining a better understanding of the relationship between glucocorticoid excess and circulating appetite signals will contribute greatly to improvements in personalized obesity prevention and treatment.
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Affiliation(s)
- Susanne Kuckuck
- Department of Internal Medicine, Division of Endocrinology, Erasmus MC, Rotterdam, Netherlands.,Obesity Center CGG, Erasmus MC, Room Rg528, P.O. Box 2040, Rotterdam, 3000 CA, Netherlands
| | - Eline S van der Valk
- Department of Internal Medicine, Division of Endocrinology, Erasmus MC, Rotterdam, Netherlands.,Obesity Center CGG, Erasmus MC, Room Rg528, P.O. Box 2040, Rotterdam, 3000 CA, Netherlands
| | - Anton J W Scheurink
- Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen, Netherlands
| | - Bibian van der Voorn
- Department of Internal Medicine, Division of Endocrinology, Erasmus MC, Rotterdam, Netherlands.,Obesity Center CGG, Erasmus MC, Room Rg528, P.O. Box 2040, Rotterdam, 3000 CA, Netherlands
| | - Anand M Iyer
- Department of Internal Medicine, Division of Endocrinology, Erasmus MC, Rotterdam, Netherlands.,Obesity Center CGG, Erasmus MC, Room Rg528, P.O. Box 2040, Rotterdam, 3000 CA, Netherlands
| | - Jenny A Visser
- Department of Internal Medicine, Division of Endocrinology, Erasmus MC, Rotterdam, Netherlands
| | - Patric J D Delhanty
- Department of Internal Medicine, Division of Endocrinology, Erasmus MC, Rotterdam, Netherlands
| | - Sjoerd A A van den Berg
- Department of Internal Medicine, Division of Endocrinology, Erasmus MC, Rotterdam, Netherlands.,Department of Clinical Chemistry, Erasmus MC, Rotterdam, Netherlands
| | - Elisabeth F C van Rossum
- Department of Internal Medicine, Division of Endocrinology, Erasmus MC, Rotterdam, Netherlands.,Obesity Center CGG, Erasmus MC, Room Rg528, P.O. Box 2040, Rotterdam, 3000 CA, Netherlands
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Purinergic receptor: a crucial regulator of adipose tissue functions. Purinergic Signal 2023; 19:273-281. [PMID: 36515790 PMCID: PMC9984650 DOI: 10.1007/s11302-022-09907-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Accepted: 11/14/2022] [Indexed: 12/15/2022] Open
Abstract
Obesity is a public-health challenge resulting from an imbalance between energy expenditure and calorie intake. This health problem exacerbates a variety of metabolic complications worldwide. Adipose tissue is an essential regulator of energy homeostasis, and the functions within it are regulated by purinergic receptors. A1R, P2X7R, and P2YR mainly mediate energy homeostasis primarily through regulating energy storage and adipokines secretion in white adipose tissue (WAT). P2X5R is a novel-specific cell surface marker in brown/beige adipocytes. A2R is a promising therapeutic target for stimulating energy expenditure in brown adipose tissue (BAT) and also mediating WAT browning. Based on these features, purinergic receptors may be an appropriate target in treating obesity. In this review, the role of purinergic receptors in different types of adipose tissue is summarized. An improved understanding of purinergic receptor functions in adipose tissue may lead to more effective treatment interventions for obesity and its related metabolic disorders.
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Regensburger M, Rasul Chaudhry S, Yasin H, Zhao Y, Stadlbauer A, Buchfelder M, Kinfe T. Emerging roles of leptin in Parkinson's disease: Chronic inflammation, neuroprotection and more? Brain Behav Immun 2023; 107:53-61. [PMID: 36150585 DOI: 10.1016/j.bbi.2022.09.010] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Revised: 08/22/2022] [Accepted: 09/16/2022] [Indexed: 12/13/2022] Open
Abstract
An increasing body of experimental evidence implicates a relationship between immunometabolic deterioration and the progression of Parkinson's disease (PD) with a dysregulation of central and peripheral neuroinflammatory networks mediated by circulating adipokines, in particular leptin. We screened the current literature on the role of adipokines in PD. Hence, we searched known databases (PubMed, MEDLINE/OVID) and reviewed original and review articles using the following terms: "leptin/ObR", "Parkinson's disease", "immune-metabolism", "biomarkers" and "neuroinflammation". Focusing on leptin, we summarize and discuss the existing in vivo and in vitro evidence on how adipokines may be protective against neurodegeneration, but at the same time contribute to the progression of PD. These components of the adipose brain axis represent a hitherto underestimated pathway to study systemic influences on dopaminergic degeneration. In addition, we give a comprehensive update on the potential of adjunctive therapeutics in PD targeting leptin, leptin-receptors, and associated pathways. Further experimental and clinical trials are needed to elucidate the mechanisms of action and the value of central and peripheral adipose-immune-metabolism molecular phenotyping in order to develop and validate the differential roles of different adipokines as potential therapeutic target for PD patients.
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Affiliation(s)
- Martin Regensburger
- Department of Molecular Neurology, Friedrich-Alexander University (FAU), Erlangen-Nürnberg, 91054 Erlangen, Germany; Center for Rare Diseases Erlangen (ZSEER), University Hospital Erlangen, 91054 Erlangen, Germany
| | - Shafqat Rasul Chaudhry
- Obaid Noor Institute of Medical Sciences (ONIMS), Mianwali, Pakistan; Shifa College of Pharmaceutical Sciences, Shifa Tameer-e-Millat University, 44000 Islamabad, Pakistan
| | - Hammad Yasin
- Shifa College of Pharmaceutical Sciences, Shifa Tameer-e-Millat University, 44000 Islamabad, Pakistan
| | - Yining Zhao
- Department of Neurosurgery, Friedrich-Alexander University (FAU), Erlangen-Nürnberg, 91054 Erlangen, Germany
| | - Andreas Stadlbauer
- Department of Neurosurgery, Friedrich-Alexander University (FAU), Erlangen-Nürnberg, 91054 Erlangen, Germany
| | - Michael Buchfelder
- Department of Neurosurgery, Friedrich-Alexander University (FAU), Erlangen-Nürnberg, 91054 Erlangen, Germany
| | - Thomas Kinfe
- Division of Functional Neurosurgery and Stereotaxy, Friedrich-Alexander University (FAU), Erlangen-Nürnberg, 91054 Erlangen, Germany.
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Apelin Promotes Prostate Cancer Metastasis by Downregulating TIMP2 via Increases in miR-106a-5p Expression. Cells 2022; 11:cells11203285. [PMID: 36291151 PMCID: PMC9600532 DOI: 10.3390/cells11203285] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Revised: 10/04/2022] [Accepted: 10/13/2022] [Indexed: 11/17/2022] Open
Abstract
Prostate cancer commonly affects the urinary tract of men and metastatic prostate cancer has a very low survival rate. Apelin belongs to the family of adipokines and is associated with cancer development and metastasis. However, the effects of apelin in prostate cancer metastasis is undetermined. Analysis of the database revealed a positive correlation between apelin level with the progression and metastasis of prostate cancer patients. Apelin treatment facilitates cell migration and invasion through inhibiting tissue inhibitor of metalloproteinase 2 (TIMP2) expression. The increasing miR-106a-5p synthesis via c-Src/PI3K/Akt signaling pathway is controlled in apelin-regulated TIMP2 production and cell motility. Importantly, apelin blockade inhibits prostate cancer metastasis in the orthotopic mouse model. Thus, apelin is a promising therapeutic target for curing metastatic prostate cancer.
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33
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Kurt Tunagur EM, Yazici AB, Guzel D, Tunagur MT, Ermis C, Suda MA, Yazici E. Investigating associations between appetite-regulating hormones, aggression and craving in males with cannabis use disorder. Drug Alcohol Depend 2022; 238:109577. [PMID: 35905593 DOI: 10.1016/j.drugalcdep.2022.109577] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Revised: 06/23/2022] [Accepted: 07/11/2022] [Indexed: 11/18/2022]
Abstract
BACKGROUND Aggression and craving are common and important withdrawal symptoms in cannabis use disorder. The present study investigated the association between appetite-regulating hormones, aggression, and craving during cannabis withdrawal syndrome (CWS). METHODS Fifty-six male subjects diagnosed with cannabis withdrawal and 45 healthy males were included in the study. The Substance Craving Scale, the Buss-Perry Aggression Questionnaire, and the State-Trait Anxiety Inventory were implemented at baseline. Blood samples were drawn to measure ghrelin, leptin, adiponectin, and resistin levels in the serum. Then, the Point Subtraction Aggression Paradigm (PSAP) was applied. Bloodwork and psychometric assessment procedures were re-implemented after the PSAP. At the 7-day follow-up, psychometric assessments and hormone measurements were repeated in the CWS group. RESULTS Baseline serum ghrelin and adiponectin levels were lower in the CWS group than controls at baseline. After PSAP, there was a significant increase in ghrelin levels of patients with CWS compared to controls. Patients yielded higher aggression scores, while there was no significant correlation between hormonal changes and PSAP findings. At 7-day follow, ghrelin and resistin levels significantly increased, while serum leptin decreased in patients with CWS. Finally, there was a positive association between craving and resistin levels. CONCLUSIONS Our results present the changes in appetite-regulating hormones. Long-term follow-up studies are needed to shed light on neuroendocrinological aspects of cannabis withdrawal.
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Affiliation(s)
| | | | - Derya Guzel
- Department of Physiology, Sakarya University, 54290 Sakarya, Turkey
| | | | - Cagatay Ermis
- Diyarbakır Children's Hospital, 21000 Diyarbakır, Turkey
| | - Mehmet Akif Suda
- Department of Psychiatry, Sakarya University, 54290 Sakarya, Turkey
| | - Esra Yazici
- Department of Psychiatry, Sakarya University, 54290 Sakarya, Turkey
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Blood and Urinary Biomarkers of Antipsychotic-Induced Metabolic Syndrome. Metabolites 2022; 12:metabo12080726. [PMID: 36005598 PMCID: PMC9416438 DOI: 10.3390/metabo12080726] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 07/29/2022] [Accepted: 08/03/2022] [Indexed: 12/15/2022] Open
Abstract
Metabolic syndrome (MetS) is a clustering of at least three of the following five medical conditions: abdominal obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum high-density lipoprotein (HDL). Antipsychotic (AP)-induced MetS (AIMetS) is the most common adverse drug reaction (ADR) of psychiatric pharmacotherapy. Herein, we review the results of studies of blood (serum and plasma) and urinary biomarkers as predictors of AIMetS in patients with schizophrenia (Sch). We reviewed 1440 studies examining 38 blood and 19 urinary metabolic biomarkers, including urinary indicators involved in the development of AIMetS. Among the results, only positive associations were revealed. However, at present, it should be recognized that there is no consensus on the role of any particular urinary biomarker of AIMetS. Evaluation of urinary biomarkers of the development of MetS and AIMetS, as one of the most common concomitant pathological conditions in the treatment of patients with psychiatric disorders, may provide a key to the development of strategies for personalized prevention and treatment of the condition, which is considered a complication of AP therapy for Sch in clinical practice.
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Kujawska A, Kujawski S, Kozakiewicz M, Hajec W, Kwiatkowska M, Skierkowska N, Husejko J, Newton JL, Zalewski P, Kędziora-Kornatowska K. Adipokines Level and Cognitive Function-Disturbance in Homeostasis in Older People with Poorly Managed Hypertension: A Pilot Study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19116467. [PMID: 35682051 PMCID: PMC9180904 DOI: 10.3390/ijerph19116467] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Revised: 05/20/2022] [Accepted: 05/24/2022] [Indexed: 11/16/2022]
Abstract
Aim: To explore the network relationship between cognitive function, depressive symptom intensity, body composition, proxies of cognitive reserve, trophic factor, adipokines and myokines, physical performance and blood pressure in a group of older people with poorly managed hypertension (PMHTN) compared to a normotensive (NTN) group. Materials and methods: History of hypertension and blood pressure level were examined in older participants. Thirty-one subjects diagnosed with PMHTN (history of hypertension diagnosis and values of sBP or dBP over 140/90 mmHg) and eighteen NTN (lack of history of hypertension and sBP and dBP lower than 140/90 mmHg) participated. Participants completed physical and cognitive function assessments: including the Mini–Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) and its two subtests Delayed Recall (DR) and Verbal Fluency (VF) and Trail Making Test Part B (TMT B). Factors associated with cognitive functioning: age, years of education, cognitive and travel activity were assessed using a questionnaire. Visceral fat was determined by bioimpedance testing and gait velocity and agility assessed using an Up and Go test. To summarize the strength and direction (negative or positive) of a relationship between two variables, Spearman’s rank correlation coefficient was used. Then, network graphs were created to illustrate the relationship between variables. Node strength (number of edges per node), neighbourhood connectivity (the average connectivity of all the neighbours of a node), stress (the number of shortest paths passing through each node) were compared in network from PMHTN group to network from NTN group. Results: Neighbourhood connectivity and stress were significantly higher in of the PMHTN network compared to NTN (6.03 ± 1.5 vs. 4.23 ± 2.5, p = 0.005 and 118.21 ± 137.6 vs. 56.87 ± 101.5, p = 0.02, accordingly). Conclusion: In older subjects with poorly managed hypertension, dyshomeostasis was observed, compared to normotensive subjects.
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Affiliation(s)
- Agnieszka Kujawska
- Department of Human Physiology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 85-092 Bydgoszcz, Poland
- Correspondence:
| | - Sławomir Kujawski
- Department of Exercise Physiology and Functional Anatomy, Ludwik Rydygier Collegium Medicum in Bydgoszcz Nicolaus Copernicus University in Torun, Świętojańska 20, 85-077 Bydgoszcz, Poland; (S.K.); (P.Z.)
| | - Mariusz Kozakiewicz
- Department of Geriatrics, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 85-094 Bydgoszcz, Poland; (M.K.); (W.H.); (M.K.); (N.S.); (J.H.); (K.K.-K.)
| | - Weronika Hajec
- Department of Geriatrics, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 85-094 Bydgoszcz, Poland; (M.K.); (W.H.); (M.K.); (N.S.); (J.H.); (K.K.-K.)
| | - Małgorzata Kwiatkowska
- Department of Geriatrics, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 85-094 Bydgoszcz, Poland; (M.K.); (W.H.); (M.K.); (N.S.); (J.H.); (K.K.-K.)
| | - Natalia Skierkowska
- Department of Geriatrics, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 85-094 Bydgoszcz, Poland; (M.K.); (W.H.); (M.K.); (N.S.); (J.H.); (K.K.-K.)
| | - Jakub Husejko
- Department of Geriatrics, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 85-094 Bydgoszcz, Poland; (M.K.); (W.H.); (M.K.); (N.S.); (J.H.); (K.K.-K.)
| | - Julia L. Newton
- Population Health Sciences Institute, The Medical School, Newcastle University, Newcastle-Upon-Tyne NE2 4AX, UK;
| | - Paweł Zalewski
- Department of Exercise Physiology and Functional Anatomy, Ludwik Rydygier Collegium Medicum in Bydgoszcz Nicolaus Copernicus University in Torun, Świętojańska 20, 85-077 Bydgoszcz, Poland; (S.K.); (P.Z.)
- Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, Warsaw Medical University, 1b Banacha Street, 02-097 Warsaw, Poland
| | - Kornelia Kędziora-Kornatowska
- Department of Geriatrics, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 85-094 Bydgoszcz, Poland; (M.K.); (W.H.); (M.K.); (N.S.); (J.H.); (K.K.-K.)
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Terzo S, Calvi P, Nuzzo D, Picone P, Galizzi G, Caruana L, Di Carlo M, Lentini L, Puleio R, Mulè F, Amato A. Preventive Impact of Long-Term Ingestion of Chestnut Honey on Glucose Disorders and Neurodegeneration in Obese Mice. Nutrients 2022; 14:nu14040756. [PMID: 35215406 PMCID: PMC8879402 DOI: 10.3390/nu14040756] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 02/04/2022] [Accepted: 02/09/2022] [Indexed: 12/11/2022] Open
Abstract
The purpose of the present study was to evaluate the impact of long-term honey ingestion on metabolic disorders and neurodegeneration in mice fed a high-fat diet (HFD). Three groups of mice were fed with a standard diet (STD), HFD or HFD supplemented with honey (HFD-H) for 16 weeks. Biochemical, histological, Western blotting, RT-PCR and Profiler PCR array were performed to assess metabolic parameters, peripheral and central insulin resistance and neurodegeneration. Daily honey intake prevented the HFD-induced glucose dysmetabolism. In fact, it reduced plasma fasting glucose, insulin and leptin concentrations and increased adiponectin levels. It improved glucose tolerance, insulin sensitivity and HOMA index without affecting plasma lipid concentration. HFD mice showed a significantly higher number of apoptotic nuclei in the superficial and deep cerebral cortex, upregulation of Fas-L, Bim and P27 (neuronal pro-apoptotic markers) and downregulation of Bcl-2 and BDNF (anti-apoptotic factors) in comparison with STD- and HFD-H mice, providing evidence for honey neuroprotective effects. PCR-array analysis showed that long-term honey intake increased the expression of genes involved in insulin sensitivity and decreased genes involved in neuroinflammation or lipogenesis, suggesting improvement of central insulin resistance. The expressions of p-AKT and p-GSK3 in HFD-H mice, which were decreased and increased, respectively, in HFD mouse brain, index of central insulin resistance, were similar to STD animals supporting the ability of regular honey intake to protect brain neurons from insulin resistance. In conclusion, the present results provide evidence for the beneficial preventative impact of regular honey ingestion on neuronal damage caused by HFD.
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Affiliation(s)
- Simona Terzo
- Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Università degli Studi di Palermo, 90128 Palermo, Italy; (S.T.); (P.C.); (D.N.); (P.P.); (L.L.); (F.M.)
| | - Pasquale Calvi
- Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Università degli Studi di Palermo, 90128 Palermo, Italy; (S.T.); (P.C.); (D.N.); (P.P.); (L.L.); (F.M.)
- Dipartmento di Biomedicina, Neuroscienze e Diagnostica Avanzata (Bi.N.D.), Università degli Studi di Palermo, 90127 Palermo, Italy
| | - Domenico Nuzzo
- Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Università degli Studi di Palermo, 90128 Palermo, Italy; (S.T.); (P.C.); (D.N.); (P.P.); (L.L.); (F.M.)
- Istituto per la Ricerca e l’Innovazione Biomedica (IRIB), CNR, via U. La Malfa 153, 90146 Palermo, Italy; (G.G.); (L.C.); (M.D.C.)
| | - Pasquale Picone
- Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Università degli Studi di Palermo, 90128 Palermo, Italy; (S.T.); (P.C.); (D.N.); (P.P.); (L.L.); (F.M.)
- Istituto per la Ricerca e l’Innovazione Biomedica (IRIB), CNR, via U. La Malfa 153, 90146 Palermo, Italy; (G.G.); (L.C.); (M.D.C.)
| | - Giacoma Galizzi
- Istituto per la Ricerca e l’Innovazione Biomedica (IRIB), CNR, via U. La Malfa 153, 90146 Palermo, Italy; (G.G.); (L.C.); (M.D.C.)
| | - Luca Caruana
- Istituto per la Ricerca e l’Innovazione Biomedica (IRIB), CNR, via U. La Malfa 153, 90146 Palermo, Italy; (G.G.); (L.C.); (M.D.C.)
| | - Marta Di Carlo
- Istituto per la Ricerca e l’Innovazione Biomedica (IRIB), CNR, via U. La Malfa 153, 90146 Palermo, Italy; (G.G.); (L.C.); (M.D.C.)
| | - Laura Lentini
- Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Università degli Studi di Palermo, 90128 Palermo, Italy; (S.T.); (P.C.); (D.N.); (P.P.); (L.L.); (F.M.)
| | - Roberto Puleio
- Istituto Zooprofilattico Sperimentale della Sicilia “Adelmo Mirri”, 90129 Palermo, Italy;
| | - Flavia Mulè
- Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Università degli Studi di Palermo, 90128 Palermo, Italy; (S.T.); (P.C.); (D.N.); (P.P.); (L.L.); (F.M.)
| | - Antonella Amato
- Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Università degli Studi di Palermo, 90128 Palermo, Italy; (S.T.); (P.C.); (D.N.); (P.P.); (L.L.); (F.M.)
- Correspondence: ; Tel.: +39-091-2389-7506
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Anti-depressive-like behaviors of APN KO mice involve Trkb/BDNF signaling related neuroinflammatory changes. Mol Psychiatry 2022; 27:1047-1058. [PMID: 34642455 DOI: 10.1038/s41380-021-01327-3] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 09/08/2021] [Accepted: 09/27/2021] [Indexed: 12/26/2022]
Abstract
Major depression disorder is a severe mental illness often linked with metabolic disorders. Adiponectin is an adipocyte-secreted circulatory hormone with antidiabetic and glucose/lipid modulation capacities. Studies have demonstrated the pathophysiological roles of adiponectin involved in various neurological disorders, including depression. However, the underlying mechanisms are poorly understood. Here we showed that adiponectin deprivation enhanced antidepressive-like behaviors in the LPS-induced model of depression. APN KO mice displayed increased cytokines (both pro and anti-inflammatory), accompanied by an impaired expression of adiponectin receptors (mRNA/protein level) and decreasing IBA-1 level in the cortex and primary microglia of LPS treated APN KO mice. Further, LPS-treatment significantly reduced p-NFκB expression in the microglia of APN KO mice. However, the Bay11-7082 treatment recovered p-NFκB expression in the cortex of APN KO mice in the presence of LPS. Interestingly, the antidepressant potentials of APN KO mice were abolished by TrkB antagonist K252a, IKK inhibitor Bay11-7082, and AdipoRon suggesting crosstalk between TrkB/BDNF signaling and NFκB in depression. Furthermore, the effects of Bay11-7082 were abolished by a TrkB/BDNF activator (7,8-DHF), indicating a critical role of TrkB/BDNF signaling. Taken together, these findings showed that dysregulated neuroinflammatory status and BDNF signaling might underlie the antidepressive-like behaviors of APN KO mice. NFκB elicited BDNF changes may be accountable for the pathogenesis of LPS induced depression, where APN might present an alternative therapeutic target for depressive disorders.
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Ekraminasab S, Dolatshahi M, Sabahi M, Mardani M, Rashedi S. The Interactions between Adipose Tissue Secretions and Parkinson's disease; The Role of Leptin. Eur J Neurosci 2022; 55:873-891. [PMID: 34989050 DOI: 10.1111/ejn.15594] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Revised: 12/30/2021] [Accepted: 12/31/2021] [Indexed: 11/30/2022]
Abstract
Leptin is a hormone that regulates appetite by acting on receptors in the hypothalamus, where it modifies food intake to maintain equilibrium with the body energy resources. Leptin and its receptors are widely distributed in the central nervous system, suggesting that they may give neuronal survival signals. The potential of leptin to decrease/increase neuronal damage and neuronal plasticity in Parkinson's diseases (PD) is the subject of this review, which outlines our current knowledge of how leptin acts in the brain. Although leptin-mediated neuroprotective signaling results in neuronal death prevention, it can affect neuroinflammatory cascades and also neuronal plasticity which contribute to PD pathology. Other neuroprotective molecules, such as insulin and erythropoietin, share leptin-related signaling cascades, and therefore constitute a component of the neurotrophic effects mediated by endogenous hormones. With the evidence that leptin dysregulation causes increased neuronal vulnerability to damage in PD, using leptin as a target for therapeutic modification is an appealing and realistic option.
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Affiliation(s)
- Sara Ekraminasab
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.,NeuroImaging Network (NIN), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Mahsa Dolatshahi
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.,NeuroImaging Network (NIN), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Mohammadmahdi Sabahi
- NeuroImaging Network (NIN), Universal Scientific Education and Research Network (USERN), Tehran, Iran.,Neurosurgery Research Group (NRG), Student Research Committee, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Mahta Mardani
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Sina Rashedi
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
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Guo M, Li D, Feng Y, Li M, Yang B. Adipose-derived stem cell-derived extracellular vesicles inhibit neuroblastoma growth by regulating GABBR1 activity through LINC00622-mediated transcription factor AR. J Leukoc Biol 2022; 111:19-32. [PMID: 34448502 DOI: 10.1002/jlb.1mia0321-164r] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Neuroblastoma (NB) is a huge threat to children's health. Adipose-derived stem cells-derived extracellular vesicles (ADSC-Evs) can regulate tumor progression. This study aimed to identify the role of ADSC-Evs in NB. Following ADSC-Ev isolation and identification, PKH26-labeled ADSC-Evs were cocultured with NB cells to observe the internalization of ADSC-Evs. ADSC-Ev effects on NB cell proliferation, invasion, and migration were assessed. The regulatory molecules related to NB development were predicted. The expressions of and relations among LINC00622, transcriptional factor androgen receptor (AR), and gamma-aminobutyric acid B-type receptor 1 (GABRR1) were detected and verified. LINC00622 was inhibited in ADSCs to evaluate ADSC-Ev effects on NB cells. Xenograft tumor experiment in nude mice was further performed to evaluate the effects of ADSC-Evs-carried LINC00622 on NB in vivo. ADSC-Evs inhibited NB cell proliferation, invasion, and migration. ADSC-Evs increased GABBR1 expression in NB cells. ADSC-Evs-carried LINC00622 mediated AR to promote GABBR1 expression. Silencing LINC00622 in ADSCs weakened the inhibition of ADSC-Evs on NB cell malignant behaviors. ADSC-Evs reduced tumor growth in nude mice, which was restored after inhibiting LINC00622 expression in ADSCs. We highlighted that ADSC-Evs carried LINC00622 into NB cells to inhibit transcription factor AR and promote GABBR1 expression, thus inhibiting NB cell growth.
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Affiliation(s)
- Mengguo Guo
- Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Province, China
| | - Dongpeng Li
- Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Province, China
| | - Yawen Feng
- Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Province, China
| | - Mu Li
- Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Province, China
| | - Bo Yang
- Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Province, China
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Joo YH, Lee MW, Son YD, Chang KA, Yaqub M, Kim HK, Cumming P, Kim JH. In Vivo Cerebral Translocator Protein (TSPO) Binding and Its Relationship with Blood Adiponectin Levels in Treatment-Naïve Young Adults with Major Depression: A [ 11C]PK11195 PET Study. Biomedicines 2021; 10:biomedicines10010034. [PMID: 35052718 PMCID: PMC8773340 DOI: 10.3390/biomedicines10010034] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 12/05/2021] [Accepted: 12/20/2021] [Indexed: 12/15/2022] Open
Abstract
Adiponectin is an adipokine that mediates cellular cholesterol efflux and plays important roles in neuroinflammatory processes. In this study, we undertook positron emission tomography (PET) with the translocator protein (TSPO) ligand [11C]PK11195 and measured serum adiponectin levels in groups of treatment-naïve young adult patients with major depressive disorder (MDD) and matched healthy controls. Thirty treatment-naïve MDD patients (median age: 24 years) and twenty-three healthy controls underwent [11C]PK11195 PET. We quantified TSPO availability in brain as the [11C]PK11195 binding potential (BPND) using a reference tissue model in conjunction with the supervised cluster analysis (SVCA4) algorithm. Age, sex distribution, body mass index, and serum adiponectin levels did not differ between the groups. Between-group analysis using a region-of-interest approach showed significantly higher [11C]PK11195 BPND in the left anterior and right posterior cingulate cortices in MDD patients than in controls. Serum adiponectin levels had significant negative correlations with [11C]PK11195 BPND in the bilateral hippocampus in MDD patients, but significant positive correlations in the bilateral hippocampus in the control group. Our results indicate significantly higher TSPO binding in the anterior and posterior cingulate cortices in treatment-naïve young MDD patients, suggesting microglial activation in these limbic regions, which are involved in cognitive and emotional processing. The opposite correlations between [11C]PK11195 BPND in the hippocampus with serum adiponectin levels in MDD and control groups suggest that microglial activation in the hippocampus may respond differentially to adiponectin signaling in MDD and healthy subjects, possibly with respect to microglial phenotype.
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Affiliation(s)
- Yo-Han Joo
- Neuroscience Research Institute, Gachon University, Incheon 21565, Korea; (Y.-H.J.); (M.-W.L.); (Y.-D.S.); (K.-A.C.); (H.-K.K.)
| | - Min-Woo Lee
- Neuroscience Research Institute, Gachon University, Incheon 21565, Korea; (Y.-H.J.); (M.-W.L.); (Y.-D.S.); (K.-A.C.); (H.-K.K.)
| | - Young-Don Son
- Neuroscience Research Institute, Gachon University, Incheon 21565, Korea; (Y.-H.J.); (M.-W.L.); (Y.-D.S.); (K.-A.C.); (H.-K.K.)
- Department of Biomedical Engineering, College of Health Science, Gachon University, Incheon 21936, Korea
- Gachon Advanced Institute for Health Science and Technology, Graduate School, Gachon University, Incheon 21565, Korea
| | - Keun-A Chang
- Neuroscience Research Institute, Gachon University, Incheon 21565, Korea; (Y.-H.J.); (M.-W.L.); (Y.-D.S.); (K.-A.C.); (H.-K.K.)
- Gachon Advanced Institute for Health Science and Technology, Graduate School, Gachon University, Incheon 21565, Korea
- Department of Pharmacology, Gachon University College of Medicine, Gachon University, Incheon 21936, Korea
| | - Maqsood Yaqub
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, 1081 HV Amsterdam, The Netherlands;
| | - Hang-Keun Kim
- Neuroscience Research Institute, Gachon University, Incheon 21565, Korea; (Y.-H.J.); (M.-W.L.); (Y.-D.S.); (K.-A.C.); (H.-K.K.)
- Department of Biomedical Engineering, College of Health Science, Gachon University, Incheon 21936, Korea
- Gachon Advanced Institute for Health Science and Technology, Graduate School, Gachon University, Incheon 21565, Korea
| | - Paul Cumming
- Department of Nuclear Medicine, Inselspital, Bern University, CH-3010 Bern, Switzerland;
- School of Psychology and Counselling, Queensland University of Technology, Brisbane 4059, Australia
| | - Jong-Hoon Kim
- Neuroscience Research Institute, Gachon University, Incheon 21565, Korea; (Y.-H.J.); (M.-W.L.); (Y.-D.S.); (K.-A.C.); (H.-K.K.)
- Gachon Advanced Institute for Health Science and Technology, Graduate School, Gachon University, Incheon 21565, Korea
- Department of Psychiatry, Gachon University College of Medicine, Gil Medical Center, Gachon University, Incheon 21565, Korea
- Correspondence: ; Tel.: +82-32-460-2696
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Yucel Gencoglu A, Irkec M, Kocabeyoglu S, Dikmen ZG, Karakaya J, Konstas AGP. Plasma levels of sirtuin and adiponectin in patients with primary open-angle glaucoma, exfoliative glaucoma, and healthy controls. Eur J Ophthalmol 2021; 32:2893-2898. [PMID: 34878321 DOI: 10.1177/11206721211065216] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
PURPOSE To compare plasma levels of sirtuin 1 (SIRT1) and adiponectin (APN) in patients with primary open-angle glaucoma (POAG), exfoliative glaucoma (XFG), and healthy control subjects. METHODS This prospective case-control study collected plasma samples from 118 participants. All subjects underwent a comprehensive ophthalmologic examination before the acquisition of a plasma sample. Plasma samples were obtained from 40 POAG, 38 XFG, and 40 healthy control subjects without any evidence of systemic or ocular disease. Serum SIRT1 and APN levels were estimated by an enzyme-linked immunosorbent assay, ELISA (Elabscience, Houston, USA) method. Statistical analysis of results relied on Kolmogorov-Smirnov, Kruskal-Wallis, Chi-square, analysis of variance (ANOVA) tests, and linear regression analysis, where appropriate. RESULTS A significant decrease in SIRT1 levels was observed in POAG patients compared to healthy controls (p = 0.004, Dunn's test). In contrast, no difference was detected between XFG and POAG patients or healthy controls (p = 0.32 and p = 0.34, respectively, Dunn's test). There was no significant difference in plasma APN levels between the three groups under investigation (p = 0.59, ANOVA). CONCLUSION Alterations in serum level of SIRT1 may suggest a possible role in POAG via potential effects in neuroprotection and oxidative stress.
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Affiliation(s)
- Aysun Yucel Gencoglu
- Department of Ophthalmology, 64005University of Health Sciences, 64113Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey
| | - Murat Irkec
- Department of Ophthalmology, 64005Hacettepe University School of Medicine, Ankara, Turkey
| | - Sibel Kocabeyoglu
- Department of Ophthalmology, 64005Hacettepe University School of Medicine, Ankara, Turkey
| | - Z Gunnur Dikmen
- Department of Biochemistry, 64005Hacettepe University School of Medicine, Ankara, Turkey
| | - Jale Karakaya
- Department of Biostatistics, 64005Hacettepe University School of Medicine, Ankara, Turkey
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Pano O, Martínez-Lapiscina EH, Sayón-Orea C, Martinez-Gonzalez MA, Martinez JA, Sanchez-Villegas A. Healthy diet, depression and quality of life: A narrative review of biological mechanisms and primary prevention opportunities. World J Psychiatry 2021; 11:997-1016. [PMID: 34888169 PMCID: PMC8613751 DOI: 10.5498/wjp.v11.i11.997] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Revised: 06/19/2021] [Accepted: 08/27/2021] [Indexed: 02/06/2023] Open
Abstract
Unipolar depressive disorder (UDD) affects more than 264 million people worldwide and was projected well before the severe acute respiratory syndrome coronavirus 2 pandemic to be the leading cause of disability-adjusted life years lost in 2030. It is imperative for leading economies to implement preventive strategies targeted towards UDD, given consistent policies are currently lacking. Recently established similarities between the aetiological hypotheses of depression and cardiometabolic diseases are shifting paradigms within this field. It is believed that dietary practices could potentially reduce the incidence of depression; similar to their effects on metabolism. Thus, the aim of this review was to compile current evidence on healthy dietary patterns as suitable contributors towards primary prevention strategies against UDD. Most of the well-known biological mechanisms behind depression have been positively associated with healthful diets and dietary patterns to varying degrees. Interestingly, a common factor of UDD is the production and overall effects of inflammatory cytokines, such as interleukin-6, tumor necrosis factor-α, and C-reactive protein. These compounds have been associated with depressive symptoms, disturbances in neuroendocrine function, leaky gut, monoamine activity and brain function, while also being key factors in the development of cardiometabolic diseases. The Mediterranean diet (MD) in particular, is well supported by first-level evidence regarding its preventive qualities against metabolic and cardiovascular diseases and thus considered a model for healthy eating by various organizations. In one of the few clinical trials investigating these associations, the PREDIMED trial, individuals with diabetes assigned to a MD supplemented with mixed tree nuts experienced a 41% relative risk reduction for developing depression. Lastly, there is a need to include health related quality of life as an indicator of physical and mental well-being, considering its putative associations with depression and suicide risk. Going forward, focusing on clinical trials, using precise nutritional assessments, and identifying nutritional biomarkers which may be related to depression are needed to fully support the implementation of dietary recommendations in the field of psychiatry.
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Affiliation(s)
- Octavio Pano
- Preventive Medicine and Public Health, University of Navarre, Pamplona 31008, Spain
| | - Elena H Martínez-Lapiscina
- Department of Neurology Center of Neuroimmunology, Hospital Clinic of Barcelona, Institut d’Investigacions Biomèdiques August Pi Sunyer, Barcelona 08036, Spain
| | - Carmen Sayón-Orea
- Department of Preventive Medicine and Public Health, University of Navarra, Pamplona 31008, Spain
- IdiSNA, Navarra Institute for Health Research, Pamplona 31008, Spain
- Department of Public Health, Navarra Institute of Public Health and Epidemiology, Pamplona 31003, Spain
| | - Miguel Angel Martinez-Gonzalez
- Preventive Medicine and Public Health, University of Navarre, Pamplona 31008, Spain
- CIBER Pathophysiology of Obesity and Nutrition, Institute of Health Carlos III, Madrid 28049, Spain
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, United States
| | - Jose Alfredo Martinez
- IdiSNA, Navarra Institute for Health Research, Pamplona 31008, Spain
- CIBER Pathophysiology of Obesity and Nutrition, Institute of Health Carlos III, Madrid 28049, Spain
- Department of Food Sciences and Physiology, University of Navarre, Pamplona 31008, Spain
- Precision Nutrition and Cardiometabolic Health Program, IMDEA Food Institute, Madrid 28049, Spain
| | - Almudena Sanchez-Villegas
- CIBER Pathophysiology of Obesity and Nutrition, Institute of Health Carlos III, Madrid 28049, Spain
- Department of Clinical Sciences, University of Las Palmas Gran Canaria, Las Palmas Gran Canaria 35080, Spain
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Würfel M, Breitfeld J, Gebhard C, Scholz M, Baber R, Riedel-Heller SG, Blüher M, Stumvoll M, Kovacs P, Tönjes A. Interplay between adipose tissue secreted proteins, eating behavior and obesity. Eur J Nutr 2021; 61:885-899. [PMID: 34636987 PMCID: PMC8854280 DOI: 10.1007/s00394-021-02687-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Accepted: 09/19/2021] [Indexed: 12/15/2022]
Abstract
Purpose Adipokines may play an important role in the complex etiology of human obesity and its metabolic complications. Here, we analyzed the relationship between 15 adipokines, eating behavior and body-mass index (BMI). Methods The study included 557 participants of the Sorbs (62.1% women, 37.9% men) and 3101 participants of the population-based LIFE-Adult cohorts (53.4% women, 46.4% men) who completed the German version of the Three-Factor-Eating Questionnaire to assess the eating behavior types cognitive restraint, disinhibition and hunger. Serum levels of 15 adipokines, including adiponectin, adipocyte fatty acid-binding protein (AFABP), angiopoietin-related growth factor (AGF), chemerin, fibroblast growth factor (FGF)-19, FGF-21, FGF-23, insulin-like growth factor (IGF)-1, interleukin (IL) 10, irisin, progranulin, vaspin, pro-neurotensin (pro-NT), pro-enkephalin (PENK) and leptin were measured. Based on significant correlations between several adipokines with different eating behavior items and BMI, we conducted mediation analyses, considering the eating behavior items as potential mediation variable towards BMI. Results Here, we found that the positive association between chemerin, AFABP or leptin and BMI in Sorbian women was mediated by higher restraint or disinhibited eating, respectively. Additionally, in Sorbian women, the negative relation between IGF-1 and BMI was mediated by higher disinhibition and the positive link between AGF and BMI by lower disinhibition. In Sorbian men, the negative relationship between PENK and BMI was mediated by lower disinhibition and hunger, whereas the negative relation between IGF-1 and BMI was mediated by higher hunger. In the LIFE-Adult women´s cohort, associations between chemerin and BMI were mediated by decreased hunger or disinhibition, respectively, whereas relations between PENK and BMI were fully mediated by decreased disinhibition. Conclusion Our study suggests that adipokines such as PENK, IGF-1, chemerin, AGF, AFABP and leptin might affect the development of obesity by directly modifying individual eating behavior. Given the observational nature of the study, future experimental or mechanistic work is warranted. Supplementary Information The online version contains supplementary material available at 10.1007/s00394-021-02687-w.
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Affiliation(s)
- Marleen Würfel
- Department of Medicine III, Division of Endocrinology, Nephrology and Rheumatology, University of Leipzig, Liebigstr. 18, 04103, Leipzig, Germany
| | - Jana Breitfeld
- Department of Medicine III, Division of Endocrinology, Nephrology and Rheumatology, University of Leipzig, Liebigstr. 18, 04103, Leipzig, Germany
| | - Claudia Gebhard
- Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG), Helmholtz Center Munich at the University of Leipzig and the University of Leipzig Medical Center, Leipzig, Germany
| | - Markus Scholz
- Institute for Medical Informatics, Statistics and Epidemiology, Medical Faculty, University of Leipzig, Leipzig, Germany.,LIFE Research Centre for Civilization Diseases, Leipzig, Germany
| | - Ronny Baber
- LIFE Research Centre for Civilization Diseases, Leipzig, Germany
| | - Steffi G Riedel-Heller
- Medical Faculty, Institute of Social Medicine, Occupational Health and Public Health (ISAP), University of Leipzig, Leipzig, Germany
| | - Matthias Blüher
- Department of Medicine III, Division of Endocrinology, Nephrology and Rheumatology, University of Leipzig, Liebigstr. 18, 04103, Leipzig, Germany.,Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG), Helmholtz Center Munich at the University of Leipzig and the University of Leipzig Medical Center, Leipzig, Germany
| | - Michael Stumvoll
- Department of Medicine III, Division of Endocrinology, Nephrology and Rheumatology, University of Leipzig, Liebigstr. 18, 04103, Leipzig, Germany
| | - Peter Kovacs
- Department of Medicine III, Division of Endocrinology, Nephrology and Rheumatology, University of Leipzig, Liebigstr. 18, 04103, Leipzig, Germany.,German Center for Diabetes Research (DZD), Neuherberg, Germany
| | - Anke Tönjes
- Department of Medicine III, Division of Endocrinology, Nephrology and Rheumatology, University of Leipzig, Liebigstr. 18, 04103, Leipzig, Germany.
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Perdoncin M, Konrad A, Wyner JR, Lohana S, Pillai SS, Pereira DG, Lakhani HV, Sodhi K. A Review of miRNAs as Biomarkers and Effect of Dietary Modulation in Obesity Associated Cognitive Decline and Neurodegenerative Disorders. Front Mol Neurosci 2021; 14:756499. [PMID: 34690698 PMCID: PMC8529023 DOI: 10.3389/fnmol.2021.756499] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Accepted: 09/10/2021] [Indexed: 12/12/2022] Open
Abstract
There has been a progressive increase in the prevalence of obesity and its comorbidities such as type 2 diabetes and cardiovascular diseases worldwide. Recent studies have suggested that the crosstalk between adipose tissue and central nervous system (CNS), through cellular mediators and signaling pathways, may causally link obesity with cognitive decline and give rise to neurodegenerative disorders. Several mechanisms have been proposed in obesity, including inflammation, oxidative stress, insulin resistance, altered lipid and cholesterol homeostasis, which may result in neuroinflammation, altered brain insulin signaling, amyloid-beta (Aβ) deposition and neuronal cell death. Since obesity is associated with functional and morphological alterations in the adipose tissues, the resulting peripheral immune response augments the development and progression of cognitive decline and increases susceptibility of neurodegenerative disorders, such as Alzheimer's Disease (AD) and Parkinson's Disease (PD). Studies have also elucidated an important role of high fat diet in the exacerbation of these clinical conditions. However, the underlying factors that propel and sustain this obesity associated cognitive decline and neurodegeneration, remains highly elusive. Moreover, the mechanisms linking these phenomena are not well-understood. The cumulative line of evidence have demonstrated an important role of microRNAs (miRNAs), a class of small non-coding RNAs that regulate gene expression and transcriptional changes, as biomarkers of pathophysiological conditions. Despite the lack of utility in current clinical practices, miRNAs have been shown to be highly specific and sensitive to the clinical condition being studied. Based on these observations, this review aims to assess the role of several miRNAs and aim to elucidate underlying mechanisms that link obesity with cognitive decline and neurodegenerative disorders. Furthermore, this review will also provide evidence for the effect of dietary modulation which can potentially ameliorate cognitive decline and neurodegenerative diseases associated with obesity.
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Affiliation(s)
| | | | | | | | | | | | | | - Komal Sodhi
- Department of Surgery and Biomedical Sciences, Marshall University Joan C. Edwards School of Medicine, Huntington, WV, United States
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The "Adipo-Cerebral" Dialogue in Childhood Obesity: Focus on Growth and Puberty. Physiopathological and Nutritional Aspects. Nutrients 2021; 13:nu13103434. [PMID: 34684432 PMCID: PMC8539184 DOI: 10.3390/nu13103434] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Revised: 09/18/2021] [Accepted: 09/21/2021] [Indexed: 01/08/2023] Open
Abstract
Overweight and obesity in children and adolescents are overwhelming problems in western countries. Adipocytes, far from being only fat deposits, are capable of endocrine functions, and the endocrine activity of adipose tissue, resumable in adipokines production, seems to be a key modulator of central nervous system function, suggesting the existence of an “adipo-cerebral axis.” This connection exerts a key role in children growth and puberty development, and it is exemplified by the leptin–kisspeptin interaction. The aim of this review was to describe recent advances in the knowledge of adipose tissue endocrine functions and their relations with nutrition and growth. The peculiarities of major adipokines are briefly summarized in the first paragraph; leptin and its interaction with kisspeptin are focused on in the second paragraph; the third paragraph deals with the regulation of the GH-IGF axis, with a special focus on the model represented by growth hormone deficiency (GHD); finally, old and new nutritional aspects are described in the last paragraph.
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Wang W, Guo J, Wang D. Promotion of chemerin in rat diabetic kidney disease through enhancement of TGF-β1/Smads/CTGF pathway. Am J Transl Res 2021; 13:10206-10217. [PMID: 34650691 PMCID: PMC8507004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Accepted: 07/31/2021] [Indexed: 06/13/2023]
Abstract
OBJECTIVE Although increasing evidence shows that the adipokine chemerin is involved in diabetic kidney disease (DKD), it is still unclear whether the chemerin acts as a critical element in renal function through the signaling pathways of transforming growth factor β1/Smads/connective tissue growth factor (TGF-β1/Smads/CTGF) in the context of DKD. Therefore, we sought to determine the role of chemerin and TGF-β1/Smads/CTGF signaling pathway in the development and/or progression of DKD. METHODS We used rat renal mesangial cells (RMCs) and a DKD rat model as study subjects. RMCs and rats were randomly separated into different groups and transfected with the constructed chemerin expression vector pcDNA™ 3.1 (+)-chemerin. Rat renal function and inflammatory cytokines were assessed after treatment with chemerin or CCX832 (ChemR23 antagonist). Real time polymerase chain reverse transcription (RT-QPCR) was used to detect the mRNA expressions of TGF-β1, Smad2, Smad4, and CTGF. Western blot was performed to determine protein expression for semiquantitative analysis. RESULTS In in vitro studies, the mRNA and protein levels of TGF-β1, Smad2, Smad4, and CTGF were significantly increased in the groups of high glucose and chemerin as compared to the normal control and normal glucose groups, most notably in the high glucose chemerin group (all P<0.05). In vivo studies revealed that the mRNA and protein levels of TGF-β1, Smad2, Smad4, and CTGF were higher in the DKD group and the normal chemerin group than in the normal control group and the blocking receptor group, while appearing the highest in the DKD chemerin group (all P<0.05). Moreover, kidney/body weight ratio, urea, creatinine, and urine protein were increased, and the weight and endogenous creatinine clearance rate decreased in the DKD group and the normal chemerin group (all P<0.05). These changes were more pronounced in the DKD chemerin group. At the same time, blood glucose, triglycerides (TGs), and total cholesterol (TC) in the blocked receptor group was lower than those in the DKD group and the DKD chemerin group (all P<0.05). In contrast to those in the normal control group and blocked receptor group, tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1 showed higher concentrations in the DKD group and the normal chemerin group. This result was more pronounced in the DKD chemerin group (all P<0.05). CONCLUSION Chemerin may play a role in DKD by enhancing the signaling pathways of TGF-β1/Smads/CTGF transduction either in vitro or in vivo. Moreover, high glucose accelerates kidney injury by activating fibrotic pathways.
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Affiliation(s)
- Weiwei Wang
- Department of Emergency, Tianjin First Central HospitalTianjin, China
| | - Jun Guo
- Tianjin Medical UniversityTianjin, China
| | - Dongqiang Wang
- Department of Integration of Traditional Chinese and Western Medicine, Tianjin First Central HospitalTianjin, China
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Pham Vu T, Can Van M, Dang Thanh C, Nguyen Minh T, Nguyen Trung K, Nguyen Duy T, Do Q, Tran Viet T, Le Viet T. Association of serum adiponectin and leptin levels with renal function in kidney transplant recipients with or without new-onset diabetes after transplantation. J Clin Lab Anal 2021; 35:e24000. [PMID: 34519108 PMCID: PMC8551688 DOI: 10.1002/jcla.24000] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2021] [Revised: 08/31/2021] [Accepted: 09/01/2021] [Indexed: 12/20/2022] Open
Abstract
PURPOSE To evaluate serum adiponectin and leptin concentration in new-onset diabetes after transplantation (NODAT) and non-NODAT patients and association with renal function in kidney transplant recipients (KTRs). PATIENTS AND METHODS A study of 314 consecutive adults KTRs divided into four groups: 236 individuals without NODAT who had renal insufficiency (RI; n = 56) or normal renal function (n = 180) and 78 patients with NODAT who had RI (n = 17) or normal renal function (n = 61). NODAT was diagnosed based on venous fasting blood glucose or HbA1c with the criteria of the American Diabetes Association. Renal insufficiency was defined according to KDOQI 2002 guidelines. RESULTS In the NODAT group, the median level of serum adiponectin was lower than that of non-NODAT one (30 µg/ml vs 37.15 µg/ml, p < 0.001); in contrast, the median leptin concentration was higher (4.27 ng/ml vs 4.05 ng/ml, p = 0.024). In the RI group, both median serum adiponectin and leptin levels were higher than those of non-RI one (Adiponectin: 40.01 µg/ml vs 33.7 µg/ml; Leptin: 4.51 ng/ml vs 3.91 ng/ml, p < 0.001 both). We found that BMI was related to both adiponectin and leptin levels in both NODAT, non-NODAT, and all subject groups, based on univariate and multivariate linear regression analysis. CONCLUSION New-onset diabetes after transplantation, BMI, and renal insufficiency were affected to the serum level of adiponectin and leptin in KTRs.
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Affiliation(s)
- Thuy Pham Vu
- Kinh 7 Charity ClinicKien GiangViet Nam
- Vietnam Military Medical UniversityHa NoiViet Nam
| | - Mao Can Van
- Vietnam Military Medical UniversityHa NoiViet Nam
| | | | | | - Kien Nguyen Trung
- Vietnam Military Medical UniversityHa NoiViet Nam
- Military Hospital 103Ha NoiViet Nam
| | - Toan Nguyen Duy
- Vietnam Military Medical UniversityHa NoiViet Nam
- Military Hospital 103Ha NoiViet Nam
| | - Quyet Do
- Vietnam Military Medical UniversityHa NoiViet Nam
| | - Tien Tran Viet
- Vietnam Military Medical UniversityHa NoiViet Nam
- Military Hospital 103Ha NoiViet Nam
| | - Thang Le Viet
- Vietnam Military Medical UniversityHa NoiViet Nam
- Military Hospital 103Ha NoiViet Nam
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48
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Fontana L, Ghezzi L, Cross AH, Piccio L. Effects of dietary restriction on neuroinflammation in neurodegenerative diseases. J Exp Med 2021; 218:211666. [PMID: 33416892 PMCID: PMC7802371 DOI: 10.1084/jem.20190086] [Citation(s) in RCA: 59] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Revised: 09/29/2020] [Accepted: 11/30/2020] [Indexed: 12/11/2022] Open
Abstract
Recent and accumulating work in experimental animal models and humans shows that diet has a much more pervasive and prominent role than previously thought in modulating neuroinflammatory and neurodegenerative mechanisms leading to some of the most common chronic central nervous system (CNS) diseases. Chronic or intermittent food restriction has profound effects in shaping brain and peripheral metabolism, immunity, and gut microbiome biology. Interactions among calorie intake, meal frequency, diet quality, and the gut microbiome modulate specific metabolic and molecular pathways that regulate cellular, tissue, and organ homeostasis as well as inflammation during normal brain aging and CNS neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis, among others. This review discusses these findings and their potential application to the prevention and treatment of CNS neuroinflammatory diseases and the promotion of healthy brain aging.
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Affiliation(s)
- Luigi Fontana
- Charles Perkins Center, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.,Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, Australia.,Department of Clinical and Experimental Sciences, Brescia University, Brescia, Italy
| | - Laura Ghezzi
- Department of Neurology, Washington University in St. Louis, St. Louis, MO.,University of Milan, Milan, Italy
| | - Anne H Cross
- Department of Neurology, Washington University in St. Louis, St. Louis, MO
| | - Laura Piccio
- Department of Neurology, Washington University in St. Louis, St. Louis, MO.,Brain and Mind Centre, School of Medical Sciences, University of Sydney, Sydney, New South Wales, Australia
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Angelopoulou E, Paudel YN, Bougea A, Piperi C. Impact of the apelin/APJ axis in the pathogenesis of Parkinson's disease with therapeutic potential. J Neurosci Res 2021; 99:2117-2133. [PMID: 34115895 DOI: 10.1002/jnr.24895] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 05/07/2021] [Accepted: 05/12/2021] [Indexed: 12/18/2022]
Abstract
The pathogenesis of Parkinson's disease (PD) remains elusive. There is still no available disease-modifying strategy against PD, whose management is mainly symptomatic. A growing amount of preclinical evidence shows that a complex interplay between autophagy dysregulation, mitochondrial impairment, endoplasmic reticulum stress, oxidative stress, and excessive neuroinflammation underlies PD pathogenesis. Identifying key molecules linking these pathological cellular processes may substantially aid in our deeper understanding of PD pathophysiology and the development of novel effective therapeutic approaches. Emerging preclinical evidence indicates that apelin, an endogenous neuropeptide acting as a ligand of the orphan G protein-coupled receptor APJ, may play a key neuroprotective role in PD pathogenesis, via inhibition of apoptosis and dopaminergic neuronal loss, autophagy enhancement, antioxidant effects, endoplasmic reticulum stress suppression, as well as prevention of synaptic dysregulation in the striatum, excessive neuroinflammation, and glutamate-induced excitotoxicity. Underlying signaling pathways involve phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin, extracellular signal-regulated kinase 1/2, and inositol requiring kinase 1α/XBP1/C/EBP homologous protein. Herein, we discuss the role of apelin/APJ axis and associated molecular mechanisms on the pathogenesis of PD in vitro and in vivo and provide evidence for its challenging therapeutic potential.
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Affiliation(s)
- Efthalia Angelopoulou
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece.,Department of Neurology, Eginition University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Yam Nath Paudel
- Neuropharmacology Research Laboratory, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Malaysia
| | - Anastasia Bougea
- Department of Neurology, Eginition University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Christina Piperi
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece
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50
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Signoriello E, Mallardo M, Nigro E, Polito R, Casertano S, Di Pietro A, Coletta M, Monaco ML, Rossi F, Lus G, Daniele A. Adiponectin in Cerebrospinal Fluid from Patients Affected by Multiple Sclerosis Is Correlated with the Progression and Severity of Disease. Mol Neurobiol 2021; 58:2663-2670. [PMID: 33486671 PMCID: PMC8128828 DOI: 10.1007/s12035-021-02287-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2020] [Accepted: 01/08/2021] [Indexed: 12/12/2022]
Abstract
Adiponectin exerts relevant actions in immunity and is modulated in several disorders, such as multiple sclerosis (MS). In this study, we characterized adiponectin expression and profiles in cerebrospinal fluid (CSF) from MS patients to investigate its potential relationship with the severity and progression of the disease. Total adiponectin in CSF was measured by ELISA in 66 unrelated CSF MS patients and compared with 24 age- and sex-matched controls. Adiponectin oligomer profiles were analysed by Western blotting and FPLC chromatography. Total CSF adiponectin was significantly increased in MS patients compared with controls (9.91 ng/mL vs 6.02 ng/mL) (p < 0.001). Interestingly, CSF adiponectin positively correlated with CSF IgG, and CSF/serum albumin directly correlated with CSF/serum adiponectin. Our data demonstrated that CSF adiponectin predicts a worse prognosis: patients with the progressive form of MS had higher levels compared with the relapsing remitting form; patients with higher EDSS at baseline and a higher MS severity score at 4.5-year follow-up had significantly elevated adiponectin levels with respect to patients with a less severe phenotype. Finally, the adiponectin oligomerization profile was altered in CSF from MS patients, with a significant increase in HMW and MMW. The correlation of CSF adiponectin with the severity and prognosis of MS disease confirmed the role of this adipokine in the inflammatory/immune processes of MS and suggested its use as a complementary tool to assess the severity, progression and prognosis of the disease. Further studies on larger MS cohorts are needed to clarify the contribution of adiponectin to the etiopathogenesis of MS.
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Affiliation(s)
- Elisabetta Signoriello
- Centro di Sclerosi Multipla, II Clinica Neurologica, Università della Campania "Luigi Vanvitelli", Via S. Pansini 5, 80131, Naples, Italy
| | - Marta Mallardo
- Dipartimento di Scienze e Tecnologie Ambientali Biologiche Farmaceutiche, Università degli Studi della Campania, "Luigi Vanvitelli", Via G. Vivaldi 42, 81100, Caserta, Italy
- CEINGE-Biotecnologie Avanzate Scarl, Via G. Salvatore 486, 80145, Naples, Italy
| | - Ersilia Nigro
- Dipartimento di Scienze e Tecnologie Ambientali Biologiche Farmaceutiche, Università degli Studi della Campania, "Luigi Vanvitelli", Via G. Vivaldi 42, 81100, Caserta, Italy
- CEINGE-Biotecnologie Avanzate Scarl, Via G. Salvatore 486, 80145, Naples, Italy
| | - Rita Polito
- CEINGE-Biotecnologie Avanzate Scarl, Via G. Salvatore 486, 80145, Naples, Italy
- Dipartimento di Sanità Pubblica, Università degli Studi di Napoli "Federico II", via Pansini 5, 80145, Naples, Italy
| | - Sara Casertano
- Centro di Sclerosi Multipla, II Clinica Neurologica, Università della Campania "Luigi Vanvitelli", Via S. Pansini 5, 80131, Naples, Italy
| | - Andrea Di Pietro
- Centro di Sclerosi Multipla, II Clinica Neurologica, Università della Campania "Luigi Vanvitelli", Via S. Pansini 5, 80131, Naples, Italy
| | - Marcella Coletta
- Centro di Sclerosi Multipla, II Clinica Neurologica, Università della Campania "Luigi Vanvitelli", Via S. Pansini 5, 80131, Naples, Italy
| | | | - Fabiana Rossi
- Centro di Sclerosi Multipla, II Clinica Neurologica, Università della Campania "Luigi Vanvitelli", Via S. Pansini 5, 80131, Naples, Italy
| | - Giacomo Lus
- Centro di Sclerosi Multipla, II Clinica Neurologica, Università della Campania "Luigi Vanvitelli", Via S. Pansini 5, 80131, Naples, Italy
| | - Aurora Daniele
- Dipartimento di Scienze e Tecnologie Ambientali Biologiche Farmaceutiche, Università degli Studi della Campania, "Luigi Vanvitelli", Via G. Vivaldi 42, 81100, Caserta, Italy.
- CEINGE-Biotecnologie Avanzate Scarl, Via G. Salvatore 486, 80145, Naples, Italy.
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