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Chen Q, Wang J, Li K, Luan JQ, Li JM, Wang YT. Irisin in thyroid diseases. Clin Chim Acta 2025; 564:119929. [PMID: 39154700 DOI: 10.1016/j.cca.2024.119929] [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: 07/12/2024] [Revised: 08/14/2024] [Accepted: 08/15/2024] [Indexed: 08/20/2024]
Abstract
Irisin, a hormone-like adipo-myokine, has garnered considerable attention in recent years for its potential impact in metabolic diseases. Its physiological effects are similar to those of thyroid hormones, prompting numerous investigations into potential correlations and interactions between irisin and thyroid function through various in vitro and animal experiments. However, existing studies suggest that the relationship between irisin and thyroid diseases is highly complex and multifaceted. In this paper, we have summarized the research results on serum irisin and thyroid function, providing an overview of advancements and constraints in current research on irisin and thyroid hormones. The aim is to offer insights and directions for future clinical trials in this field.
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Affiliation(s)
- Qi Chen
- Department of outpatient, Shijiazhuang No.8 Retired Cadre Retirement Home of Hebei Military Region, Shijiazhuang 050000, China
| | - Jing Wang
- Department of Cardionephrology, Hospital affiliated to NCO School of Army Military Medical University, Shijiazhuang 050000, China
| | - Kang Li
- Department of oncology, hematology and endocrinology, Hospital affiliated to NCO School of Army Military Medical University, Shijiazhuang 050000, China
| | - Jun-Qin Luan
- Clinical laboratory, Hospital affiliated to NCO School of Army Military Medical University, Shijiazhuang 050000, China
| | - Jing-Mei Li
- Department of oncology, hematology and endocrinology, Hospital affiliated to NCO School of Army Military Medical University, Shijiazhuang 050000, China
| | - Ya-Ting Wang
- Department of oncology, hematology and endocrinology, Hospital affiliated to NCO School of Army Military Medical University, Shijiazhuang 050000, China.
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Valladolid-Acebes I. Hippocampal Leptin Resistance and Cognitive Decline: Mechanisms, Therapeutic Strategies and Clinical Implications. Biomedicines 2024; 12:2422. [PMID: 39594988 PMCID: PMC11591892 DOI: 10.3390/biomedicines12112422] [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: 09/13/2024] [Revised: 10/17/2024] [Accepted: 10/17/2024] [Indexed: 11/28/2024] Open
Abstract
Background: Leptin, an adipokine essential for regulating energy balance, exerts important effects on brain function, notably within the hippocampus, a region integral to learning and memory. Leptin resistance, characterized by diminished responsiveness to elevated leptin levels, disrupts hippocampal function and exacerbates both obesity and cognitive impairments. Scope: This review critically examines how leptin resistance impairs hippocampal synaptic plasticity processes, specifically affecting long-term potentiation (LTP) and long-term depression (LTD), which are crucial for cognitive performance. Findings: Recent research highlights that leptin resistance disrupts N-methyl-D-aspartate (NMDA) receptor dynamics and hippocampal structure, leading to deficits in spatial learning and memory. Additionally, high-fat diets (HFDs), which contribute to leptin resistance, further deteriorate hippocampal function. Potential therapeutic strategies, including leptin sensitizers, show promise in mitigating brain disorders associated with leptin resistance. Complementary interventions such as caloric restriction and physical exercise also enhance leptin sensitivity and offer potential benefits to alleviating cognitive impairments. Aims of the review: This review synthesizes recent findings on the molecular pathways underlying leptin resistance and its impact on synaptic transmission and plasticity in the hippocampus. By identifying potential therapeutic targets, this work aims to provide an integrated approach for addressing cognitive deficits in obesity, ultimately improving the quality of life for affected individuals.
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Affiliation(s)
- Ismael Valladolid-Acebes
- The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Karolinska University Hospital L1, SE-171 76 Stockholm, Sweden
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Wang D, Wang G, Wang X, Ren Z, Jia C. Native Mass Spectrometry-Centric Approaches Revealed That Neuropeptides Frequently Interact with Amyloid-β. ACS Chem Neurosci 2024; 15:2719-2728. [PMID: 39066700 DOI: 10.1021/acschemneuro.4c00075] [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] [Indexed: 07/30/2024] Open
Abstract
Amyloid-β (Aβ) aggregates are recognized as initiators of Alzheimer's disease, and their interaction with the nervous system contributes to the progression of neurodegeneration. Herein, we investigated the frequency at which neuropeptides interact with Aβ and affect the aggregation kinetics and cytotoxicity of Aβ. To this end, we established a native mass spectrometry (MS)-centric workflow for screening Aβ-interacting neuropeptides, and six out of 12 neuropeptides formed noncovalent complexes with Aβ species in the MS gas phase. Thioflavin-T fluorescence assays and gel separation indicated that leptin and cerebellin decreased Aβ aggregation, whereas kisspeptin increased this process. In addition, leptin and cerebellin attenuated Aβ-induced cytotoxicity, which was independent of the influence of metal ions. Leptin can chelate copper from copper-bound Aβ species, reducing the cytotoxicity caused by the aggregation of Aβ and metal ion complexes. Overall, our study demonstrated that neuropeptides frequently interact with Aβ and revealed that leptin and cerebellin are potential inhibitors of Aβ aggregation, providing great insight into understanding the molecular mechanism of Aβ interacting with the nervous system and facilitating drug development.
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Affiliation(s)
- Danyang Wang
- Department of Anatomy, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, China
- Beijing Proteome Research Center, State Key Laboratory of Medical Proteomics, Beijing Institute of Lifeomics, National Center for Protein Sciences-Beijing, Beijing 102206, China
| | - Guibin Wang
- Beijing Proteome Research Center, State Key Laboratory of Medical Proteomics, Beijing Institute of Lifeomics, National Center for Protein Sciences-Beijing, Beijing 102206, China
| | - Xiankun Wang
- Beijing Proteome Research Center, State Key Laboratory of Medical Proteomics, Beijing Institute of Lifeomics, National Center for Protein Sciences-Beijing, Beijing 102206, China
| | - Zhenhua Ren
- Department of Anatomy, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, China
| | - Chenxi Jia
- Department of Anatomy, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, China
- Beijing Proteome Research Center, State Key Laboratory of Medical Proteomics, Beijing Institute of Lifeomics, National Center for Protein Sciences-Beijing, Beijing 102206, China
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Shao W, Su Y, Liu J, Liu Y, Zhao J, Fan X. Understanding the link between different types of maternal diabetes and the onset of autism spectrum disorders. DIABETES & METABOLISM 2024; 50:101543. [PMID: 38761920 DOI: 10.1016/j.diabet.2024.101543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Revised: 05/03/2024] [Accepted: 05/04/2024] [Indexed: 05/20/2024]
Abstract
Autism spectrum disorders (ASD) encompass a collection of neurodevelopmental disorders that exhibit impaired social interactions and repetitive stereotypic behaviors. Although the exact cause of these disorders remains unknown, it is widely accepted that both genetic and environmental factors contribute to their onset and progression. Recent studies have highlighted the potential negative impact of maternal diabetes on embryonic neurodevelopment, suggesting that intrauterine hyperglycemia could pose an additional risk to early brain development and contribute to the development of ASD. This paper presents a comprehensive analysis of the current research on the relationship between various forms of maternal diabetes, such as type 1 diabetes mellitus, type 2 diabetes mellitus, and gestational diabetes mellitus, and the likelihood of ASD in offspring. The study elucidates the potential mechanisms through which maternal hyperglycemia affects fetal development, involving metabolic hormones, immune dysregulation, heightened oxidative stress, and epigenetic alterations. The findings of this review offer valuable insights for potential preventive measures and evidence-based interventions targeting ASD.
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Affiliation(s)
- Wenyu Shao
- Department of Military Cognitive Psychology, School of Psychology, Third Military Medical University (Army Medical University), Chongqing, China
| | - Yichun Su
- Department of Military Cognitive Psychology, School of Psychology, Third Military Medical University (Army Medical University), Chongqing, China
| | - Jiayin Liu
- Department of Military Cognitive Psychology, School of Psychology, Third Military Medical University (Army Medical University), Chongqing, China
| | - Yulong Liu
- Department of Military Cognitive Psychology, School of Psychology, Third Military Medical University (Army Medical University), Chongqing, China
| | - Jinghui Zhao
- Department of Military Cognitive Psychology, School of Psychology, Third Military Medical University (Army Medical University), Chongqing, China.
| | - Xiaotang Fan
- Department of Military Cognitive Psychology, School of Psychology, Third Military Medical University (Army Medical University), Chongqing, China
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Maylem ERS, Schütz LF, Spicer LJ. The role of asprosin in regulating ovarian granulosa- and theca-cell steroidogenesis: a review with comparisons to other adipokines. Reprod Fertil Dev 2024; 36:RD24027. [PMID: 39074236 DOI: 10.1071/rd24027] [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: 02/19/2024] [Accepted: 07/04/2024] [Indexed: 07/31/2024] Open
Abstract
Adipose tissues produce a variety of biologically active compounds, including cytokines, growth factors and adipokines. Adipokines are important as they function as endocrine hormones that are related to various metabolic and reproductive diseases. The goal of this review was to summarise the role of asprosin, a recently discovered adipokine, and compare its role in ovarian steroidogenesis with that of other adipokines including adiponectin, leptin, resistin, apelin, visfatin, chemerin, irisin, and gremlin 1. The summary of concentrations of these adipokines in humans, rats and other animals will help researchers identify appropriate doses to test in future studies. Review of the literature indicated that asprosin increases androstenedione production in theca cells (Tc), and when cotreated with FSH increases oestradiol production in granulosa cells (Gc). In comparison, other adipokines (1) stimulate Gc oestradiol production but inhibit Tc androgen production (adiponectin), (2) inhibit Gc oestradiol production and Tc androstenedione production (leptin and chemerin), (3) inhibit Gc steroidogenesis with no effect on Tc (resistin), (4) inhibit Gc oestradiol production but stimulate Tc androgen production (gremlin 1), and (5) increase steroid secretion by Gc, with unknown effects on Tc steroidogenesis (apelin and visfatin). Irisin has direct effects on Gc but its precise role (inhibitory or stimulatory) may be species dependent and its effects on Tc will require additional research. Thus, most adipokines have direct effects (either positive or negative) on steroid production in ovarian cells, but how they all work together to create a cumulative effect or disease will require further research.
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Affiliation(s)
- Excel Rio S Maylem
- Philippine Carabao Center, National Headquarters and Gene Pool, Science City of Munoz, Nueva Ecija, Philippines
| | - Luis Fernando Schütz
- Department of Agriculture, Veterinary and Rangeland Sciences, University of Nevada, Reno, NV 89557, USA
| | - Leon J Spicer
- Department of Animal and Food Sciences, Oklahoma State University, Stillwater, OK 74078, USA
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Vigouroux C, Mosbah H, Vatier C. Leptin replacement therapy in the management of lipodystrophy syndromes. ANNALES D'ENDOCRINOLOGIE 2024; 85:201-204. [PMID: 38871500 DOI: 10.1016/j.ando.2024.05.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2024]
Abstract
Lipodystrophy syndromes are rare diseases of genetic or acquired origin, characterized by quantitative and qualitative defects in adipose tissue. The metabolic consequences of lipodystrophy syndromes, such as insulin resistant diabetes, hypertriglyceridemia and hepatic steatosis, are frequently very difficult to treat, resulting in significant risks of acute and/or chronic complications and of decreased quality of life. The production of leptin by lipodystrophic adipose tissue is decreased, more severely in generalized forms of lipodystrophy, where adipose tissue is absent from almost all body fat depots, than in partial forms of the disease, where lipoatrophy affects only some parts of the body and can be associated with increased body fat in other anatomical regions. Several lines of evidence in preclinical and clinical models have shown that leptin replacement therapy could improve the metabolic complications of lipodystrophy syndromes. Metreleptin, a recombinant leptin analogue, was approved as an orphan drug to treat the metabolic complications of leptin deficiency in patients with generalized lipodystrophy in the USA or with either generalized or partial lipodystrophy in Japan and Europe. In this brief review, we will discuss the benefits and limitations of this therapy, and the new expectations arising from the recent development of a therapeutic monoclonal antibody able to activate the leptin receptor.
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Affiliation(s)
- Corinne Vigouroux
- Service d'endocrinologie, diabétologie et endocrinologie de la reproduction, centre national de référence des pathologies rares de l'insulino-secrétion et de l'insulino-sensibilité (PRISIS), hôpital Saint-Antoine, Assistance publique-Hôpitaux de Paris, Paris, France; Centre de recherche Saint-Antoine, institut hospitalo-universitaire de cardio-métabolisme et nutrition (ICAN), Sorbonne université, Inserm UMR_S 938, Paris, France.
| | - Héléna Mosbah
- Centre de recherche Saint-Antoine, institut hospitalo-universitaire de cardio-métabolisme et nutrition (ICAN), Sorbonne université, Inserm UMR_S 938, Paris, France; Service endocrinologie, diabétologie, nutrition, centre de compétence PRISIS, CHU La Milétrie, Poitiers, France; Université Paris Cité, ECEVE UMR 1123, Inserm, Paris, France
| | - Camille Vatier
- Service d'endocrinologie, diabétologie et endocrinologie de la reproduction, centre national de référence des pathologies rares de l'insulino-secrétion et de l'insulino-sensibilité (PRISIS), hôpital Saint-Antoine, Assistance publique-Hôpitaux de Paris, Paris, France; Centre de recherche Saint-Antoine, institut hospitalo-universitaire de cardio-métabolisme et nutrition (ICAN), Sorbonne université, Inserm UMR_S 938, Paris, France
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Checa-Ros A, Hsueh WC, Merck B, González-Torres H, Bermúdez V, D’Marco L. Obesity and Oral Health: The Link Between Adipokines and Periodontitis. TOUCHREVIEWS IN ENDOCRINOLOGY 2024; 20:25-31. [PMID: 38812668 PMCID: PMC11132655 DOI: 10.17925/ee.2024.20.1.7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Accepted: 09/15/2023] [Indexed: 05/31/2024]
Abstract
Periodontitis is a chronic inflammatory disease of the periodontium, or the supportive tissues around the tooth. This disease has been related to different risk factors, such as the presence of plaque and calculus, tobacco smoking, low socioeconomic status, and the immune state of the host. Importantly, the chronic inflammatory environment generated by periodontitis may lead to tooth loss and diverse systemic complications, such as cardiovascular disease, osteoarthritis and metabolic disease. Recent investigations have supported the role of obesity as a risk factor for periodontitis. Furthermore, studies have found obesity to compromise healing after periodontal therapy; however, the mechanisms underlying this association are not well understood. Proteins called 'adipokines' could be the factor linking obesity to periodontitis. Adipokines are bioactive molecules with hormonal properties and a structure similar to cytokines produced by the adipose tissue. Although adipokines have both pro-and anti-inflammatory effects, the shift towards pro-inflammatory actions occurs when the adipose tissue becomes pathological, as observe in the progression of conditions such as obesity or adiposopathy. This article reviews the role of adipokines in the pathophysiology and progression of periodontitis by focusing on their impact on inflammation and the molecular mechanisms through which adipokines contribute to the onset and development of periodontitis.
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Affiliation(s)
- Ana Checa-Ros
- Grupo de Investigación en Enfermedades Cardiorrenales y Metabólicas, Departamento de Medicina y Cirugía, Facultad de Ciencias de la Salud, Universidad Cardenal Herrera-CEU, CEU Universities, Valencia, Spain
| | - Wei-Chung Hsueh
- Departamento de Odontología, Facultad de Ciencias de la Salud, Universidad Cardenal Herrera-CEU, CEU Universities, Valencia, Spain
| | - Belén Merck
- Grupo de Investigación en Enfermedades Cardiorrenales y Metabólicas, Departamento de Medicina y Cirugía, Facultad de Ciencias de la Salud, Universidad Cardenal Herrera-CEU, CEU Universities, Valencia, Spain
| | - Henry González-Torres
- Facultad de Ciencias de la Salud, Universidad Simón Bolívar, Barranquilla, Colombia
- Centro de Investigaciones en Ciencias de la Vida, Universidad Simón Bolívar, Barranquilla, Colombia
| | - Valmore Bermúdez
- Facultad de Ciencias de la Salud, Universidad Simón Bolívar, Barranquilla, Colombia
| | - Luis D’Marco
- Grupo de Investigación en Enfermedades Cardiorrenales y Metabólicas, Departamento de Medicina y Cirugía, Facultad de Ciencias de la Salud, Universidad Cardenal Herrera-CEU, CEU Universities, Valencia, Spain
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Aguiar APN, Mendonça PDS, Lima Junior RCP, Mota AGDM, Wong DVT, Oliveira RTGD, Ribeiro-Júnior HL, Pinheiro RF, Magalhães SMM. The role of adiposity, adipokines and polymorphisms of leptin and adiponectin in myelodysplastic syndromes. Br J Nutr 2024; 131:737-748. [PMID: 37855224 DOI: 10.1017/s0007114523002283] [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] [Indexed: 10/20/2023]
Abstract
The aim of the present study was to investigate the relationship between leptin and adiponectin gene polymorphisms, circulating levels of leptin and adiponectin, adiposity and clinical markers in patients with myelodysplastic syndrome (MDS). This cross-sectional study was conducted with 102 adults and elderly MDS patients and 102 age- and sex-matched controls. Clinical characteristics, co-morbidities, anthropometric data, laboratory evaluation and genetic analysis (polymorphisms -2548G > A/rs7799039 of the LEP gene and +276G > T/rs1501299 of the ADIPOQ gene) were investigated. Serum leptin was higher and adiponectin lower in MDS when compared with controls. There was a significant positive correlation between serum leptin levels and BMI (r = 0·264, P = 0·025), waist circumference (r = 0·235, P = 0·047), body fat percentage (BF %) (r = 0·373, P = 0·001) and the fat mass index (FMI) (r = 0·371, P < 0·001). A lower mean adiponectin was found among patients with high BF %, higher visceral adiposity index and metabolic syndrome. A significant association was found between the AA genotype (mutant) of the LEP polymorphism rs7799039 and male sex and blast excess (≥ 5 %). In addition, a significant association was observed between the TT genotype (mutant) of the ADIPOQ rs1501299 polymorphism and Fe overload. These results demonstrate the importance of a comprehensive and systematic evaluation in patients with MDS in order to identify and control negative factors not related to the disease at an early stage.
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Affiliation(s)
- Ana Patrícia Nogueira Aguiar
- Cancer Cytogenomic Laboratory, Federal University of Ceará, Fortaleza, CE60430-275, Brazil
- Center for Research and Drug Development (NPDM), Federal University of Ceará, Fortaleza, CE, Brazil
| | - Priscila da Silva Mendonça
- Cancer Cytogenomic Laboratory, Federal University of Ceará, Fortaleza, CE60430-275, Brazil
- Center for Research and Drug Development (NPDM), Federal University of Ceará, Fortaleza, CE, Brazil
- University Hospital Walter Cantidio, Brazilian Company of Hospital Services (EBSERH), Fortaleza, CE, Brazil
| | - Roberto Cesar Pereira Lima Junior
- Center for Research and Drug Development (NPDM), Federal University of Ceará, Fortaleza, CE, Brazil
- Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, CE, Brazil
| | - Anacelia Gomes de Matos Mota
- Cancer Cytogenomic Laboratory, Federal University of Ceará, Fortaleza, CE60430-275, Brazil
- Center for Research and Drug Development (NPDM), Federal University of Ceará, Fortaleza, CE, Brazil
| | - Deysi Viviana Tenazoa Wong
- Center for Research and Drug Development (NPDM), Federal University of Ceará, Fortaleza, CE, Brazil
- Department of Pathology and Forensic Medicine, Federal University of Ceará, Fortaleza, CE, Brazil
| | - Roberta Tatiane Germano de Oliveira
- Cancer Cytogenomic Laboratory, Federal University of Ceará, Fortaleza, CE60430-275, Brazil
- Center for Research and Drug Development (NPDM), Federal University of Ceará, Fortaleza, CE, Brazil
| | - Howard Lopes Ribeiro-Júnior
- Cancer Cytogenomic Laboratory, Federal University of Ceará, Fortaleza, CE60430-275, Brazil
- Center for Research and Drug Development (NPDM), Federal University of Ceará, Fortaleza, CE, Brazil
| | - Ronald Feitosa Pinheiro
- Cancer Cytogenomic Laboratory, Federal University of Ceará, Fortaleza, CE60430-275, Brazil
- Center for Research and Drug Development (NPDM), Federal University of Ceará, Fortaleza, CE, Brazil
- Post-Graduate Program of Pathology, Federal University of Ceará, Fortaleza, CE, Brazil
- Department of Clinical Medicine, Federal University of Ceará, Fortaleza, CE, Brazil
- Post-graduate Program in Medical Science, Federal University of Ceará, Fortaleza, CE, Brazil
| | - Silvia Maria Meira Magalhães
- Cancer Cytogenomic Laboratory, Federal University of Ceará, Fortaleza, CE60430-275, Brazil
- Center for Research and Drug Development (NPDM), Federal University of Ceará, Fortaleza, CE, Brazil
- Department of Clinical Medicine, Federal University of Ceará, Fortaleza, CE, Brazil
- Post-graduate Program in Medical Science, Federal University of Ceará, Fortaleza, CE, Brazil
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Yang X, Deng H, Lv J, Chen X, Zeng L, Weng J, Liang H, Xu W. Comparison of changes in adipokine and inflammatory cytokine levels in patients with newly diagnosed type 2 diabetes treated with exenatide, insulin, or pioglitazone: A post-hoc study of the CONFIDENCE trial. Heliyon 2024; 10:e23309. [PMID: 38169889 PMCID: PMC10758788 DOI: 10.1016/j.heliyon.2023.e23309] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Revised: 11/23/2023] [Accepted: 11/30/2023] [Indexed: 01/05/2024] Open
Abstract
Background Adipokines and inflammatory cytokines (ADICs) play important roles in type 2 diabetes mellitus (T2DM). This study aimed to compare the changes of ADIC levels (ΔADICs) in patients with newly diagnosed T2DM treated with different antihyperglycemic agents, and further investigate the impact of these changes on metabolic indices, β-cell function and insulin resistance (IR). Methods Four hundred and sixteen patients with newly diagnosed T2DM from 25 centers in China randomly received 48-week intervention with exenatide, insulin or pioglitazone. Anthropometric and laboratory data, indices of β-cell function and IR, and levels of AIDCs, including interleukin-1 beta (IL-1β), interferon-gamma (IFN-γ), leptin, and fibroblast growth factor 21 (FGF21) were detected at baseline and the end of the study. Results In total, 281 participants (68 % male, age: 50.3 ± 9.4 years) completed the study. After 48- week treatment, IL-1β and IFN-γ were significantly decreased with exenatide treatment (P < 0.001 and P = 0.001, respectively), but increased with insulin (P = 0.009 and P = 0.026, respectively). However, pioglitazone treatment had no impact on ADICs. No significant change in leptin or FGF21 was detected with any of the treatments. After adjustment for baseline values and changes of body weight, waist and HbA1c, the between-group differences were found in ΔIL-1β (exenatide vs. insulin: P = 0.048; and exenatide vs. pioglitazone: P = 0.003, respectively) and ΔIFN-γ (exenatide vs. insulin: P = 0.049; and exenatide vs. pioglitazone: P < 0.001, respectively). Multiple linear regression analysis indicated that Δweight was associated with ΔIL-1β (β = 0.753; 95 % CI, 0.137-1.369; P = 0.017). After adjusting for treatment effects, Δweight was also be correlated with ΔFGF21 (β = 1.097; 95%CI, 0.250-1.944; P = 0.012); furthermore, ΔHOMA-IR was correlated with Δleptin (β = 0.078; 95%CI, 0.008-0.147; P = 0.029) as well. However, ΔHOMA-IR was not significantly associated with ΔIL-1β after adjusting for treatment effects (P = 0.513). Conclusion Exenatide treatment led to significant changes of inflammatory cytokines levels (IL-1β and IFN-γ), but not adipokines (leptin and FGF21), in newly diagnosed T2DM patients. The exenatide-mediated improvement in weight and IR may be associated with a decrease in inflammatory cytokine levels.
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Affiliation(s)
- Xubin Yang
- Department of Endocrinology and Metabolism, the 3rd Affiliated Hospital of Sun Yat-sen University. NO.600, Tianhe Road, Tianhe District, Guangzhou, Guangdong, 510630, China
| | - Hongrong Deng
- Department of Endocrinology and Metabolism, the 3rd Affiliated Hospital of Sun Yat-sen University. NO.600, Tianhe Road, Tianhe District, Guangzhou, Guangdong, 510630, China
| | - Jing Lv
- Department of Endocrinology and Metabolism, the 3rd Affiliated Hospital of Sun Yat-sen University. NO.600, Tianhe Road, Tianhe District, Guangzhou, Guangdong, 510630, China
| | - Xueyan Chen
- Department of Endocrinology and Metabolism, the 3rd Affiliated Hospital of Sun Yat-sen University. NO.600, Tianhe Road, Tianhe District, Guangzhou, Guangdong, 510630, China
| | - Longyi Zeng
- Department of Endocrinology and Metabolism, the 3rd Affiliated Hospital of Sun Yat-sen University. NO.600, Tianhe Road, Tianhe District, Guangzhou, Guangdong, 510630, China
| | - Jianping Weng
- Department of Endocrinology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China (USTC), Hefei, China
| | - Hua Liang
- Department of Endocrinology and Metabolism, Shunde Hospital of Southern Medical University (The First People's Hospital of Shunde), Foshan, China
| | - Wen Xu
- Department of Endocrinology and Metabolism, the 3rd Affiliated Hospital of Sun Yat-sen University. NO.600, Tianhe Road, Tianhe District, Guangzhou, Guangdong, 510630, China
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10
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Kwon OC, Park MC. Patients with systemic lupus erythematosus who are underweight have distinct disease characteristics. Lupus 2024; 33:68-74. [PMID: 38050807 DOI: 10.1177/09612033231220726] [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] [Indexed: 12/06/2023]
Abstract
OBJECTIVE This study aimed to detail the disease characteristics of systemic lupus erythematosus (SLE) in individuals who are underweight and assess whether underweight status is associated with SLE disease activity. METHODS This was a retrospective cohort study involving 218 patients newly diagnosed with SLE. Patients were categorized as underweight (body mass index [BMI] <18.5 kg/m2) or not underweight (BMI ≥18.5 kg/m2). We reviewed disease characteristics including the SLE Disease Activity Index 2000 (SLEDAI-2K) at diagnosis. High disease activity was defined as SLEDAI-2K ≥10. Disease characteristics were compared between those who were underweight and not underweight. We used multivariable logistic regression analysis to determine whether underweight status is associated with high disease activity. RESULTS Out of the 218 patients, 35 (16.1%) were underweight and 183 (83.9%) were not. Underweight patients had less renal involvement (5.7% vs 20.2%, p = .040), lower C-reactive protein levels (1.0 [0.3-2.3] mg/L vs 1.2 [0.8-5.0] mg/L, p = .028), and lower SLEDAI-2K scores (6.7 ± 4.6 vs 9.1 ± 5.7, p = .009), and were less likely to be at high disease activity status (22.9% vs 42.6%, p = .028), compared with those who were not underweight. Following adjustment for multiple covariates, being underweight was inversely associated with high disease activity status (adjusted odds ratio = 0.38, 95% confidence interval = 0.16 to 0.92, p = .031). CONCLUSION Patients with SLE who were underweight showed less renal involvement and lower SLEDAI-2K scores compared with those who were not underweight. Moreover, those with SLE who were underweight had a 60% lower risk of exhibiting high disease activity.
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Affiliation(s)
- Oh Chan Kwon
- Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Min-Chan Park
- Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
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11
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Feng J, Jia T, Ren Y, Zhang H, Zhu W. Methylation of the leptin gene promoter is associated with a negative correlation between leptin concentration and body fat in Tupaia belangeri. Life Sci 2024; 336:122323. [PMID: 38042285 DOI: 10.1016/j.lfs.2023.122323] [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: 09/23/2023] [Revised: 11/20/2023] [Accepted: 11/29/2023] [Indexed: 12/04/2023]
Abstract
AIMS Leptin is a signaling protein secreted by white adipose tissue encoded by the obesity gene, and its main function is to regulate the food intake and energy metabolism in mammals. Previous studies had found that animal leptin concentration was positively correlated with its body fat, but the leptin concentration of Tupaia belangeri was negatively correlated with its body fat mass. The present study attempted to investigate the mechanisms of leptin concentration negatively correlated with its body fat mass in T. belangeri. MATERIAL AND METHODS We measured the leptin concentration of the two groups of animals by enzyme linked immunosorbent assay (ELISA) and quantified the leptin mRNA expression by qPCR. Then, the histological, transcriptomic, and bisulfite sequencing of the two groups of animals were studied. Moreover, to investigate the energy metabolism under the negative correlation, we also analyzed the metabolomics and metabolic rate in T. belangeri. KEY FINDINGS We revealed the negative correlation was mediated by leptin gene methylation of subcutaneous adipose tissue. Further, we also found that T. belangeri increased energy metabolism with leptin decreased. SIGNIFICANCE We challenge the traditional view that leptin concentration was positively correlated with body fat mass, and further revealed its molecular mechanism and energy metabolism strategy. This special leptin secretion mechanism and energy metabolism strategy enriched our understanding of energy metabolism of animals, which provided an opportunity for the clinical transformation of metabolic diseases.
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Affiliation(s)
- Jiahong Feng
- Key Laboratory of Ecological Adaptive Evolution and Conservation on Animals-Plants in Southwest Mountain Ecosystem of Yunnan Province Higher Institutes College, School of Life Sciences, Yunnan Normal University, Kunming 650500, Yunnan, China
| | - Ting Jia
- Key Laboratory of Ecological Adaptive Evolution and Conservation on Animals-Plants in Southwest Mountain Ecosystem of Yunnan Province Higher Institutes College, School of Life Sciences, Yunnan Normal University, Kunming 650500, Yunnan, China
| | - Yue Ren
- Shanxi Agricultural University, Taiyuan 030024, Shanxi, China
| | - Hao Zhang
- Key Laboratory of Ecological Adaptive Evolution and Conservation on Animals-Plants in Southwest Mountain Ecosystem of Yunnan Province Higher Institutes College, School of Life Sciences, Yunnan Normal University, Kunming 650500, Yunnan, China
| | - Wanlong Zhu
- Key Laboratory of Ecological Adaptive Evolution and Conservation on Animals-Plants in Southwest Mountain Ecosystem of Yunnan Province Higher Institutes College, School of Life Sciences, Yunnan Normal University, Kunming 650500, Yunnan, China; Engineering Research Center of Sustainable Development and Utilization of Biomass Energy Ministry of Education, Yunnan Normal University, Kunming 650500, Yunnan, China; Key Laboratory of Yunnan Province for Biomass Energy and Environment Biotechnology, Kunming 650500, Yunnan, China.
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12
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Bir A, Ghosh A, Müller WE, Ganguly A. Mitochondrial dysfunction and metabolic syndrome. METABOLIC SYNDROME 2024:157-172. [DOI: 10.1016/b978-0-323-85732-1.00043-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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13
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Fernandois D, Vázquez MJ, Barroso A, Paredes AH, Tena-Sempere M, Cruz G. Multi-Organ Increase in Norepinephrine Levels after Central Leptin Administration and Diet-Induced Obesity. Int J Mol Sci 2023; 24:16909. [PMID: 38069231 PMCID: PMC10706686 DOI: 10.3390/ijms242316909] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Revised: 11/17/2023] [Accepted: 11/22/2023] [Indexed: 12/18/2023] Open
Abstract
Autonomic innervation is important to regulate homeostasis in every organ of the body. The sympathetic nervous system controls several organs associated with metabolism and reproduction, including adipose tissue, the liver, and the ovaries. The sympathetic nervous system is controlled within the central nervous system by neurons located in the hypothalamus, which in turn are regulated by hormones like leptin. Leptin action in the hypothalamus leads to increased sympathetic activity in the adipose tissue. In this short report, we propose that leptin action in the brain also controls the sympathetic innervation of other organs like the liver and the ovary. We performed two experiments: We performed an intracerebroventricular (ICV) injection of leptin and measured norepinephrine levels in several organs, and we used a validated model of overnutrition and obesity to evaluate whether an increase in leptin levels coexists with high levels of norepinephrine in the liver and ovaries. Norepinephrine was measured by ELISA in adipose tissue and by HPLC-EC in other tissues. Leptin was measured by ELISA. We found that the ICV injection of leptin increases norepinephrine levels in several organs, including the liver and ovaries. Also, we found that diet-induced obesity leads to an increase in leptin levels while inducing an increase in norepinephrine levels in the liver and ovaries. Finally, since hyperactivity of the sympathetic nervous system is observed both in non-alcoholic fatty liver disease and polycystic ovary syndrome, we think that an increase in norepinephrine levels induced by hyperleptinemia could be involved in the pathogenesis of both diseases.
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Affiliation(s)
- Daniela Fernandois
- Center for Neurobiochemical Studies in Endocrine Diseases, Laboratory of Neurobiochemistry, Department of Biochemistry and Molecular Biology, Faculty of Chemistry and Pharmaceutical Sciences, Universidad de Chile, Santiago 7820436, Chile; (D.F.); (A.H.P.)
| | - María Jesús Vázquez
- Department of Cell Biology, Physiology and Immunology, University of Córdoba, 14004 Cordoba, Spain; (M.J.V.); (A.B.); (M.T.-S.)
- Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, 28029 Madrid, Spain
- Instituto Maimónides de Investigación Biomédica de Córdoba, Hospital Universitario Reina Sofia, 14004 Cordoba, Spain
| | - Alexia Barroso
- Department of Cell Biology, Physiology and Immunology, University of Córdoba, 14004 Cordoba, Spain; (M.J.V.); (A.B.); (M.T.-S.)
- Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, 28029 Madrid, Spain
- Instituto Maimónides de Investigación Biomédica de Córdoba, Hospital Universitario Reina Sofia, 14004 Cordoba, Spain
| | - Alfonso H. Paredes
- Center for Neurobiochemical Studies in Endocrine Diseases, Laboratory of Neurobiochemistry, Department of Biochemistry and Molecular Biology, Faculty of Chemistry and Pharmaceutical Sciences, Universidad de Chile, Santiago 7820436, Chile; (D.F.); (A.H.P.)
| | - Manuel Tena-Sempere
- Department of Cell Biology, Physiology and Immunology, University of Córdoba, 14004 Cordoba, Spain; (M.J.V.); (A.B.); (M.T.-S.)
- Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, 28029 Madrid, Spain
- Instituto Maimónides de Investigación Biomédica de Córdoba, Hospital Universitario Reina Sofia, 14004 Cordoba, Spain
| | - Gonzalo Cruz
- Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, Valparaiso 2360102, Chile
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14
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Kokkorakis M, Katsarou A, Katsiki N, Mantzoros CS. Milestones in the journey towards addressing obesity; Past trials and triumphs, recent breakthroughs, and an exciting future in the era of emerging effective medical therapies and integration of effective medical therapies with metabolic surgery. Metabolism 2023; 148:155689. [PMID: 37689110 DOI: 10.1016/j.metabol.2023.155689] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2023] [Revised: 08/28/2023] [Accepted: 08/28/2023] [Indexed: 09/11/2023]
Abstract
The 21st century is characterized by an increasing incidence and prevalence of obesity and the burden of its associated comorbidities, especially cardiometabolic diseases, which are reaching pandemic proportions. In the late '90s, the "black box" of adipose tissue and energy homeostasis was opened with the discovery of leptin, transforming the adipose tissue from an "inert fat-storage organ" to the largest human endocrine organ and creating the basis on which more intensified research efforts to elucidate the pathogenesis of obesity and develop novel treatments were based upon. Even though leptin was eventually not proven to be the "standalone magic bullet" for the treatment of common/polygenic obesity, it has been successful in the treatment of monogenic obesity syndromes. Additionally, it shifted the paradigm of treating obesity from a condition due to "lack of willpower" to a disease due to distinct underlying biological mechanisms for which specific pharmacotherapies would be needed in addition to lifestyle modification. Subsequently, the melanocortin pathway proved to be an equally valuable pathway for the pharmacotherapy of obesity. Melanocortin receptor agonists have recently been approved for treating certain types of syndromic obesity. Other molecules- such as incretins, implicated in energy and glucose homeostasis- are secreted by the gastrointestinal tract. Glucagon-like peptide 1 (GLP-1) is the most prominent one, with GLP-1 analogs approved for common/polygenic obesity. Unimolecular combinations with other incretins, e.g., GLP-1 with gastric inhibitory polypeptide and/or glucagon, are expected to be approved soon as more effective pharmacotherapies for obesity and its comorbidities. Unimolecular combinations with other compounds and small molecules activating the receptors of these molecules are currently under investigation as promising future pharmacotherapies. Moreover, metabolic and bariatric surgery has also demonstrated impressive results, especially in the case of morbid obesity. Consequently, this broadening therapeutic armamentarium calls for a well-thought-after and well-coordinated multidisciplinary approach, for instance, through cardiometabolic expertise centers, that would ideally address effectively and cost-effectively obesity and its comorbidities, providing tangible benefits to large segments of the population.
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Affiliation(s)
- Michail Kokkorakis
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
| | - Angeliki Katsarou
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
| | - Niki Katsiki
- Department of Nutritional Sciences and Dietetics, International Hellenic University, 57400 Thessaloniki, Greece
| | - Christos S Mantzoros
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; Section of Endocrinology, VA Boston Healthcare System, Harvard Medical School, Boston, MA 02115, USA.
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15
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Ajabnoor GMA. The Molecular and Genetic Interactions between Obesity and Breast Cancer Risk. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1338. [PMID: 37512149 PMCID: PMC10384495 DOI: 10.3390/medicina59071338] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Revised: 07/14/2023] [Accepted: 07/19/2023] [Indexed: 07/30/2023]
Abstract
Breast cancer (BC) is considered the leading cause of death among females worldwide. Various risk factors contribute to BC development, such as age, genetics, reproductive factors, obesity, alcohol intake, and lifestyle. Obesity is considered to be a pandemic health problem globally, affecting millions of people worldwide. Obesity has been associated with a high risk of BC development. Determining the impact of obesity on BC development risk in women by demonstrating the molecular and genetic association in pre- and post-menopause females and risk to BC initiation is crucial in order to improve the diagnosis and prognosis of BC disease. In epidemiological studies, BC in premenopausal women was shown to be protective in a certain pattern. These altered effects between the two phases could be due to various physiological changes, such as estrogen/progesterone fluctuating levels. In addition, the relationship between BC risk and obesity is indicated by different molecular alterations as metabolic pathways and genetic mutation or epigenetic DNA changes supporting a strong connection between obesity and BC risk. However, these molecular and genetic alteration remain incompletely understood. The aim of this review is to highlight and elucidate the different molecular mechanisms and genetic changes occurring in obese women and their association with BC risk and development.
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Affiliation(s)
- Ghada M A Ajabnoor
- Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia
- Food, Nutrition and Lifestyle Unit, King Fahd Medical Research Centre, King Abdulaziz University, Jeddah 21551, Saudi Arabia
- Saudi Diabetes Research Group, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia
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16
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Niwczyk O, Grymowicz M, Szczęsnowicz A, Hajbos M, Kostrzak A, Budzik M, Maciejewska-Jeske M, Bala G, Smolarczyk R, Męczekalski B. Bones and Hormones: Interaction between Hormones of the Hypothalamus, Pituitary, Adipose Tissue and Bone. Int J Mol Sci 2023; 24:ijms24076840. [PMID: 37047811 PMCID: PMC10094866 DOI: 10.3390/ijms24076840] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2022] [Revised: 03/30/2023] [Accepted: 04/01/2023] [Indexed: 04/14/2023] Open
Abstract
The bony skeleton, as a structural foundation for the human body, is essential in providing mechanical function and movement. The human skeleton is a highly specialized and dynamic organ that undergoes continuous remodeling as it adapts to the demands of its environment. Advances in research over the last decade have shone light on the various hormones that influence this process, modulating the metabolism and structural integrity of bone. More recently, novel and non-traditional functions of hypothalamic, pituitary, and adipose hormones and their effects on bone homeostasis have been proposed. This review highlights recent work on physiological bone remodeling and discusses our knowledge, as it currently stands, on the systemic interplay of factors regulating this interaction. In this review, we provide a summary of the literature on the relationship between bone physiology and hormones including kisspeptin, neuropeptide Y, follicle-stimulating hormone (FSH), prolactin (PRL), adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), growth hormone (GH), leptin, and adiponectin. The discovery and understanding of this new functionality unveils an entirely new layer of physiologic circuitry.
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Affiliation(s)
- Olga Niwczyk
- Department of Gynecological Endocrinology, Poznan University of Medical Sciences, 60-535 Poznan, Poland
| | - Monika Grymowicz
- Department of Gynecological Endocrinology, Medical University of Warsaw, 00-315 Warsaw, Poland
| | - Aleksandra Szczęsnowicz
- Department of Gynecological Endocrinology, Poznan University of Medical Sciences, 60-535 Poznan, Poland
| | - Marta Hajbos
- Department of Gynecological Endocrinology, Medical University of Warsaw, 00-315 Warsaw, Poland
| | - Anna Kostrzak
- Department of Gynecological Endocrinology, Poznan University of Medical Sciences, 60-535 Poznan, Poland
| | - Michał Budzik
- Department of Gynecological Endocrinology, Medical University of Warsaw, 00-315 Warsaw, Poland
- Department of Cancer Prevention, Medical University of Warsaw, 02-091 Warsaw, Poland
| | - Marzena Maciejewska-Jeske
- Department of Gynecological Endocrinology, Poznan University of Medical Sciences, 60-535 Poznan, Poland
| | - Gregory Bala
- UCD School of Medicine, University College Dublin, D04 V1W8 Dublin, Ireland
| | - Roman Smolarczyk
- Department of Gynecological Endocrinology, Medical University of Warsaw, 00-315 Warsaw, Poland
| | - Błażej Męczekalski
- Department of Gynecological Endocrinology, Poznan University of Medical Sciences, 60-535 Poznan, Poland
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17
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Sharma Y, Galvão AM. Maternal obesity and ovarian failure: is leptin the culprit? Anim Reprod 2023; 19:e20230007. [PMID: 36855701 PMCID: PMC9968511 DOI: 10.1590/1984-3143-ar2023-0007] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Accepted: 01/24/2023] [Indexed: 02/22/2023] Open
Abstract
At the time of its discovery and characterization in 1994, leptin was mostly considered a metabolic hormone able to regulate body weight and energy homeostasis. However, in recent years, a great deal of literature has revealed leptin's pleiotropic nature, through its involvement in numerous physiological contexts including the regulation of the female reproductive tract and ovarian function. Obesity has been largely associated with infertility, and leptin signalling is known to be dysregulated in the ovaries of obese females. Hence, the disruption of ovarian leptin signalling was shown to contribute to the pathophysiology of ovarian failure in obese females, affecting transcriptional programmes in the gamete and somatic cells. This review attempts to uncover the underlying mechanisms contributing to female infertility associated with obesity, as well as to shed light on the role of leptin in the metabolic dysregulation within the follicle, the effects on the oocyte epigenome, and the potential long-term consequence to embryo programming.
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Affiliation(s)
- Yashaswi Sharma
- Institute of Animal Reproduction and Food Research of PAS, Department of Reproductive Immunology and Pathology, Olsztyn, Poland
| | - António Miguel Galvão
- Institute of Animal Reproduction and Food Research of PAS, Department of Reproductive Immunology and Pathology, Olsztyn, Poland,Babraham Institute, Epigenetics Programme, Cambridge, United Kingdom UK,Centre for Trophoblast Research, University of Cambridge, Cambridge, United Kingdom UK,Corresponding author: ;
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18
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Ni W, Zhang J, Wang B, Liang F, Bao L, Li P, Fang Y. Actin related protein 2/3 complex subunit 1 up-regulation in the hypothalamus prevents high-fat diet induced obesity. Eur J Neurosci 2023; 57:64-77. [PMID: 36382618 DOI: 10.1111/ejn.15871] [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: 01/28/2022] [Revised: 10/10/2022] [Accepted: 11/10/2022] [Indexed: 11/17/2022]
Abstract
Obesity is a major health crisis in the modern society. Studies have shown that the consumption of a high-fat diet (HFD) induces hypothalamic inflammation and leptin resistance, which consequently favours body mass gain. Actin related protein 2/3 complex subunit 1 (ARPC1B), an actin-binding protein, is highly expressed in immune cells. Recent studies have shown that ARPC1B has a certain anti-inflammatory effect. While ARPC1B expression is decreased in the hypothalamus of mice fed a HFD, the role of ARPC1B in HFD-induced obesity remains unclear. Thus, we investigated whether ARPC1B up-regulation in the hypothalamic arcuate nucleus (ARC) could inhibit the development of obesity. Herein, ARPC1B overexpression lentiviral particles were stereotaxically injected into the ARC of male C57BL/6J mice (7 weeks old) fed with HFD. Overexpression of ARPC1B in the hypothalamic ARC attenuated HFD-induced ARC inflammation, reduced body-weight gain and feed efficiency. Furthermore, up-regulation of ARC ARPC1B improved the glucose tolerance and reduced subcutaneous/epididymal fat mass accumulation, which decreased the serum total cholesterol, serum triglyceride and leptin levels. In addition, upon ARPC1B overexpression in the hypothalamic ARC, intraperitoneal injection of leptin increased the phosphorylation level of signal transducer and activator of transcription 3 (STAT3), an important transcription factor for leptin's action, in the ARC of obese mice. Accordingly, we suggest that up-regulation of ARPC1B in the hypothalamic ARC may improve the HFD-induced hypothalamic inflammation and leptin resistance. Our findings demonstrate that ARPC1B is a promising target for the treatment of diet-induced obesity.
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Affiliation(s)
- Weimin Ni
- Department of Neurosurgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, P.R. China
| | - Jie Zhang
- Department of Neurosurgery, Sanbo Brain Hospital Capital Medical University, Beijing, P.R. China
| | - Bing Wang
- Department of Neurosurgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, P.R. China
| | - Feng Liang
- Department of Neurosurgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, P.R. China
| | - Long Bao
- Department of Neurosurgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, P.R. China
| | - Pengfei Li
- Graduate School of Jinzhou Medical University, Jinzhou, Liaoning, P.R. China
| | - Yan Fang
- Teaching and Research Section of Anatomy, College of Basic Medical Sciences, Jinzhou Medical University, Jinzhou, Liaoning, P.R. China
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19
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Calcaterra V, Magenes VC, Rossi V, Fabiano V, Mameli C, Zuccotti G. Lipodystrophies in non-insulin-dependent children: Treatment options and results from recombinant human leptin therapy. Pharmacol Res 2023; 187:106629. [PMID: 36566927 DOI: 10.1016/j.phrs.2022.106629] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Revised: 12/10/2022] [Accepted: 12/20/2022] [Indexed: 12/24/2022]
Abstract
Lipodystrophy is a general definition containing different pathologies which, except for those observed in insulin-treated subjects falling outside the scope of this paper, are characterized by total or partial lack of body fat, that, according to the amount of missing adipose tissue, are divided in generalized or partial lipodystrophy. These diseases are characterized by leptin deficiency, which often leads to metabolic derangement, causing insulin resistance, dyslipidemia, and increasing cardiovascular risk. In this narrative review, we presentend the clinical presentation of different types of lipodystrophies and metabolic unbalances related to disease in children and adolescents, focusing on the main treatment options and the novel results from recombinant human leptin (metreleptin) therapy. Milestones in the management of lipodystrophy include lifestyle modification as diet and physical activity, paired with hypoglycemic drugs, insulin, hypolipidemic drugs, and other drugs with the aim of treating lipodystrophy complications. Metreleptin has been recently approved for pediatric patients with general lipodystrophy (GL)> 2 years of age and for children with partial lipodystrophy (PL)> 12 years of age not controlled with conventional therapies. New therapeutic strategies are currently being investigated, especially for patients with PL forms, specifically, liver-targeted therapies. Further studies are needed to achieve the most specific and precise treatment possible.
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Affiliation(s)
- Valeria Calcaterra
- Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy; Department of Pediatrics, Vittore Buzzi Children's Hospital, 20154 Milan, Italy.
| | | | - Virginia Rossi
- Department of Pediatrics, Vittore Buzzi Children's Hospital, 20154 Milan, Italy
| | - Valentina Fabiano
- Department of Pediatrics, Vittore Buzzi Children's Hospital, 20154 Milan, Italy; Department of Biomedical and Clinical Sciences, Università di Milano, 20122 Milan, Italy
| | - Chiara Mameli
- Department of Pediatrics, Vittore Buzzi Children's Hospital, 20154 Milan, Italy; Department of Biomedical and Clinical Sciences, Università di Milano, 20122 Milan, Italy
| | - Gianvincenzo Zuccotti
- Department of Pediatrics, Vittore Buzzi Children's Hospital, 20154 Milan, Italy; Department of Biomedical and Clinical Sciences, Università di Milano, 20122 Milan, Italy
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20
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Simental-Mendía LE, Simental-Mendía M, Ríos-Mier M. Effects of Coffee Supplementation on Homocysteine and Leptin Levels: A Systematic Review and Meta-analysis of Clinical Trials. Curr Pharm Des 2023; 29:30-36. [PMID: 36515040 DOI: 10.2174/1381612829666221213101827] [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: 04/28/2022] [Revised: 09/26/2022] [Accepted: 11/01/2022] [Indexed: 12/15/2022]
Abstract
BACKGROUND It has been reported that the consumption of antioxidant foods and beverages may benefit the development of cardiovascular risk factors. However, the impact of coffee consumption on some of these factors, such as homocysteine and leptin is controversial. Some clinical trials have suggested that coffee administration increases plasma total homocysteine levels, while others have found no significant changes in leptin concentrations. OBJECTIVE This study aimed to assess the effects of coffee supplementation on homocysteine and leptin concentrations in a meta-analysis of clinical trials. METHODS PubMed, Web of Science, Scopus, ClinicalTrials.gov, and Google Scholar databases were searched from inception to September 29, 2021. A fixed-effects model and the generic inverse variance weighting method were used for meta-analysis. RESULTS The meta-analysis demonstrated that coffee administration significantly increases homocysteine levels (WMD: 0.55 μmol/L, 95% CI: 0.17, 0.93, p = 0.005, I2 = 0%) but has no significant changes in leptin concentrations (WMD: 1.34 ng/mL, 95% CI: -0.78, 3.45, p = 0.21, I2 = 0%). Additionally, the sensitivity analysis was robust for both homocysteine and leptin levels. CONCLUSION The results of the present meta-analysis revealed that coffee supplementation raises serum homocysteine concentrations but has no effect on circulating leptin levels.
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Affiliation(s)
- Luis E Simental-Mendía
- Unidad de Investigación Biomédica, Instituto Mexicano del Seguro Social, Delegación Durango, México
| | - Mario Simental-Mendía
- Department of Orthopedics and Traumatology, Hospital Universitario "Dr. José E. González", Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey, NL, México
| | - Mayela Ríos-Mier
- Unidad de Investigación Biomédica, Instituto Mexicano del Seguro Social, Delegación Durango, México
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21
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Zhu J, An Y, Wang X, Huang L, Kong W, Gao M, Wang J, Sun X, Zhu S, Xie Z. The natural product rotundic acid treats both aging and obesity by inhibiting PTP1B. LIFE MEDICINE 2022; 1:372-386. [PMID: 39872740 PMCID: PMC11749463 DOI: 10.1093/lifemedi/lnac044] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/03/2022] [Accepted: 10/20/2022] [Indexed: 01/30/2025]
Abstract
The occurrence of obesity is associated with age. But their interplay remains mysterious. Here, we discovered that rotundic acid (RA), a plant-derived pentacyclic triterpene, was a powerful agent for both anti-aging and treating obesity. Considering that obese individuals decrease the appetite-suppressing and energy-expenditure-enhancing functions of leptin leading to obesity, we found RA was a leptin sensitizer, evidenced by observations that RA enhanced the leptin sensitivity to normal diet-induced obese (DIO) mice, and had minimal or no use to normal lean mice, leptin receptor-deficient (db/db) mice, and leptin-deficient (ob/ob) mice. Simultaneously, RA significantly increased energy expenditure, BAT thermogenesis, and glucose metabolism in DIO mice, as the results of enhancing leptin sensitivity. Regarding mode of action, we demonstrated that RA is a noncompetitive inhibitor of leptin negative regulators protein tyrosine phosphatase 1B (PTP1B) and T-cell PTP through interaction with their C-terminus, thus leading to weight loss through enhancing leptin sensitivity. Besides, we showed that deletion of yPTP1 in yeast completely abolished the lifespan extension effect of RA, celstrol, and withaferin A, while these compounds exhibited PTP1B inhibition activity. Furthermore, PTP1B knockdown extend lifespan in yeast and human cells, indicating PTP1B is an important factor regulating cellular aging.
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Affiliation(s)
- Jie Zhu
- Peking University International Cancer Institute and Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing 100191, China
- Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China
| | - Yongpan An
- Peking University International Cancer Institute and Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing 100191, China
| | - Xin Wang
- Peking University International Cancer Institute and Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing 100191, China
| | - Liting Huang
- Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China
| | - Weikaixin Kong
- Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00014, Finland
| | - Miaomiao Gao
- Peking University International Cancer Institute and Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing 100191, China
| | - Jingxiang Wang
- Peking University International Cancer Institute and Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing 100191, China
| | - Xinpei Sun
- Peking University International Cancer Institute and Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing 100191, China
| | - Sujie Zhu
- Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China
| | - Zhengwei Xie
- Peking University International Cancer Institute and Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing 100191, China
- Peking University - Yunnan Baiyao International Medical Research Center, Peking University Health Science Center, Beijing 100191, China
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22
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Pal SC, Eslam M, Mendez-Sanchez N. Detangling the interrelations between MAFLD, insulin resistance, and key hormones. Hormones (Athens) 2022; 21:573-589. [PMID: 35921046 DOI: 10.1007/s42000-022-00391-w] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Accepted: 07/19/2022] [Indexed: 11/04/2022]
Abstract
Metabolic dysfunction-associated fatty liver disease (MAFLD) has increasingly become a significant and highly prevalent cause of chronic liver disease, displaying a wide array of risk factors and pathophysiologic mechanisms of which only a few have so far been clearly elucidated. A bidirectional interaction between hormonal discrepancies and metabolic-related disorders, including obesity, type 2 diabetes mellitus (T2DM), and polycystic ovarian syndrome (PCOS) has been described. Since the change in nomenclature from non-alcoholic fatty liver disease (NAFLD) to MAFLD is based on the clear impact of metabolic elements on the disease, the reciprocal interactions of hormones such as insulin, adipokines (leptin and adiponectin), and estrogens have strongly pointed to the intrinsic links that lead to the heterogeneous epidemiology, clinical presentations, and risk factors involved in MAFLD in different populations. The objective of this work is twofold. Firstly, there is a brief discussion regarding the change in nomenclature as well as epidemiology, risk factors, and pathophysiologic mechanisms other than hormonal effects, which include nutrition and the gut microbiome, as well as genetic and epigenetic influences. Secondly, we review the basis of the most important hormonal factors involved in the development and progression of MAFLD that act both independently and in an interrelated manner.
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Affiliation(s)
- Shreya C Pal
- Faculty of Medicine, National Autonomous University of Mexico, Av. Universidad 3000, Coyoacán, 4510, Mexico City, Mexico
- Liver Research Unit, Medica Sur Clinic & Foundation, Puente de Piedra 150. Col. Toriello Guerra, 14050, Tlalpan, Mexico City, Mexico
| | - Mohammed Eslam
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital, University of Sydney, Sydney, NSW, Australia
| | - Nahum Mendez-Sanchez
- Faculty of Medicine, National Autonomous University of Mexico, Av. Universidad 3000, Coyoacán, 4510, Mexico City, Mexico.
- Liver Research Unit, Medica Sur Clinic & Foundation, Puente de Piedra 150. Col. Toriello Guerra, 14050, Tlalpan, Mexico City, Mexico.
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Marchi PH, Vendramini THA, Perini MP, Zafalon RVA, Amaral AR, Ochamotto VA, Da Silveira JC, Dagli MLZ, Brunetto MA. Obesity, inflammation, and cancer in dogs: Review and perspectives. Front Vet Sci 2022; 9:1004122. [PMID: 36262532 PMCID: PMC9573962 DOI: 10.3389/fvets.2022.1004122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 08/31/2022] [Indexed: 11/13/2022] Open
Abstract
Obesity is the most common nutritional disease in dogs, and its prevalence has increased in recent decades. Several countries have demonstrated a prevalence of obesity in dogs similar to that observed in humans. Chronic low-grade inflammation is a prominent basis used to explain how obesity results in numerous negative health consequences. This is well known and understood, and recent studies have pointed to the association between obesity and predisposition to specific types of cancers and their complications. Such elucidations are important because, like obesity, the prevalence of cancer in dogs has increased in recent decades, establishing cancer as a significant cause of death for these animals. In the same way, intensive advances in technology in the field of human and veterinary medicine (which even proposes the use of animal models) have optimized existing therapeutic methods, led to the development of innovative treatments, and shortened the time to diagnosis of cancer. Despite the great challenges, this review aims to highlight the evidence obtained to date on the association between obesity, inflammation, and cancer in dogs, and the possible pathophysiological mechanisms that link obesity and carcinogenesis. The potential to control cancer in animals using existing knowledge is also presented.
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Affiliation(s)
- Pedro H. Marchi
- Pet Nutrology Research Center, Department of Animal Nutrition and Production of the School of Veterinary Medicine and Animal Science, University of São Paulo, Pirassununga, Brazil
| | - Thiago H. A. Vendramini
- Pet Nutrology Research Center, Department of Animal Nutrition and Production of the School of Veterinary Medicine and Animal Science, University of São Paulo, Pirassununga, Brazil
| | - Mariana P. Perini
- Pet Nutrology Research Center, Department of Animal Nutrition and Production of the School of Veterinary Medicine and Animal Science, University of São Paulo, Pirassununga, Brazil
| | - Rafael V. A. Zafalon
- Pet Nutrology Research Center, Department of Animal Nutrition and Production of the School of Veterinary Medicine and Animal Science, University of São Paulo, Pirassununga, Brazil
| | - Andressa R. Amaral
- Veterinary Nutrology Service, Veterinary Teaching Hospital of the School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil
| | - Vanessa A. Ochamotto
- Pet Nutrology Research Center, Department of Animal Nutrition and Production of the School of Veterinary Medicine and Animal Science, University of São Paulo, Pirassununga, Brazil
| | - Juliano C. Da Silveira
- Laboratory of Molecular, Morphophysiology and Development (LMMD), Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo, Pirassununga, Brazil
| | - Maria L. Z. Dagli
- Laboratory of Experimental and Comparative Oncology, Department of Pathology, School of Veterinary Medicine and Animal Science of the University of São Paulo, São Paulo, Brazil
| | - Marcio A. Brunetto
- Pet Nutrology Research Center, Department of Animal Nutrition and Production of the School of Veterinary Medicine and Animal Science, University of São Paulo, Pirassununga, Brazil,Veterinary Nutrology Service, Veterinary Teaching Hospital of the School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil,*Correspondence: Marcio A. Brunetto
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Meriin AB, Zaarur N, Roy D, Kandror KV. Egr1 plays a major role in the transcriptional response of white adipocytes to insulin and environmental cues. Front Cell Dev Biol 2022; 10:1003030. [PMID: 36246998 PMCID: PMC9554007 DOI: 10.3389/fcell.2022.1003030] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Accepted: 09/08/2022] [Indexed: 11/18/2022] Open
Abstract
It is believed that insulin regulates metabolic functions of white adipose tissue primarily at the post-translational level via the PI3K-Akt-mediated pathway. Still, changes in transcription also play an important role in the response of white adipocytes to insulin and environmental signals. One transcription factor that is dramatically and rapidly induced in adipocytes by insulin and nutrients is called Early Growth Response 1, or Egr1. Among other functions, it directly binds to promoters of leptin and ATGL stimulating the former and inhibiting the latter. Furthermore, expression of Egr1 in adipocytes demonstrates cell autonomous circadian pattern suggesting that Egr1 not only mediates the effect of insulin and nutrients on lipolysis and leptin production but also, coordinates insulin action with endogenous circadian rhythms of adipose tissue.
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Affiliation(s)
- A. B. Meriin
- Department of Biochemistry, Boston University School of Medicine, Boston, MA, United States
| | - N. Zaarur
- Department of Biochemistry, Boston University School of Medicine, Boston, MA, United States
| | - D. Roy
- Department of Neuroscience, The Ohio State University, Columbus, OH, United States
| | - K. V. Kandror
- Department of Biochemistry, Boston University School of Medicine, Boston, MA, United States
- *Correspondence: K. V. Kandror,
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25
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Liu J, Lai F, Hou Y, Zheng R. Leptin signaling and leptin resistance. MEDICAL REVIEW (BERLIN, GERMANY) 2022; 2:363-384. [PMID: 37724323 PMCID: PMC10388810 DOI: 10.1515/mr-2022-0017] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Accepted: 07/12/2022] [Indexed: 09/20/2023]
Abstract
With the prevalence of obesity and associated comorbidities, studies aimed at revealing mechanisms that regulate energy homeostasis have gained increasing interest. In 1994, the cloning of leptin was a milestone in metabolic research. As an adipocytokine, leptin governs food intake and energy homeostasis through leptin receptors (LepR) in the brain. The failure of increased leptin levels to suppress feeding and elevate energy expenditure is referred to as leptin resistance, which encompasses complex pathophysiological processes. Within the brain, LepR-expressing neurons are distributed in hypothalamus and other brain areas, and each population of the LepR-expressing neurons may mediate particular aspects of leptin effects. In LepR-expressing neurons, the binding of leptin to LepR initiates multiple signaling cascades including janus kinase (JAK)-signal transducers and activators of transcription (STAT) phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT), extracellular regulated protein kinase (ERK), and AMP-activated protein kinase (AMPK) signaling, etc., mediating leptin actions. These findings place leptin at the intersection of metabolic and neuroendocrine regulations, and render leptin a key target for treating obesity and associated comorbidities. This review highlights the main discoveries that shaped the field of leptin for better understanding of the mechanism governing metabolic homeostasis, and guides the development of safe and effective interventions to treat obesity and associated diseases.
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Affiliation(s)
- Jiarui Liu
- Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing, China
| | - Futing Lai
- Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing, China
| | - Yujia Hou
- Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing, China
| | - Ruimao Zheng
- Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing, China
- Neuroscience Research Institute, Peking University, Beijing, China
- Key Laboratory for Neuroscience of Ministry of Education, Peking University, Beijing, China
- Key Laboratory for Neuroscience of National Health Commission, Peking University, Beijing 100191, China
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26
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Diagnosis and Drug Prediction of Parkinson's Disease Based on Immune-Related Genes. J Mol Neurosci 2022; 72:1809-1819. [PMID: 35731466 DOI: 10.1007/s12031-022-02043-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Accepted: 06/14/2022] [Indexed: 10/17/2022]
Abstract
Parkinson's disease (PD) is the second most common neurodegenerative disorder. Immune mechanisms play an important role in the development of PD. The purpose of this study was to identify potential differentially expressed immune-related genes (IRGs), signaling pathways, and drugs in PD, which may provide new diagnostic markers and therapeutic targets for PD. Differentially expressed genes (DEGs) and IRGs were respectively obtained from the Gene Expression Omnibus (GEO) dataset and the ImmPort database. Weighted gene co-expression network analysis (WGCNA) was utilized to further identify hub IRGs. Core IRGs were obtained by intersection of DEGs and hub genes in the module of WGCNA, followed by construction of diagnostic models and regulation network establishment of long non-coding RNAs (lncRNAs)-miRNAs-diagnostic IRGs. Analysis of functional enrichment and protein-protein interaction (PPI) network and identification of related drugs of DEGs was performed. LILRB3 and CSF3R were identified as potential diagnostic markers for PD. Two regulatory pairs were identified based on LILRB3 and CSF3R, including XIST-hsa-miR-214-3p/hsa-miR-761-LILRB3 and XIST-hsa-miR-485-5p/hsa-miR-654-5p-CSF3R. LEP and IL1A were drug targets of Olanzapine. MMP9 and HSP90AB1 were drug targets of Bevacizumab. In addition, LEP and MMP9 were respectively drug targets of Lovastatin and Celecoxib. Herpes simplex infection (involved TNFRSF1A) and cytokine-cytokine receptor interaction (involved CSF3R, LEP, and IL1A) were the most remarkably enriched signaling pathways of DEGs. Identified IRGs and related signaling pathways may play critical roles in the development of PD. Additionally, LILRB3 and CSF3R can be considered as potential immune-related diagnostic markers for PD. LEP, IL1A, MMP9, and HSP90AB1 may be regarded as immune-related therapeutic targets for PD.
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Grasso P. Harnessing the Power of Leptin: The Biochemical Link Connecting Obesity, Diabetes, and Cognitive Decline. Front Aging Neurosci 2022; 14:861350. [PMID: 35527735 PMCID: PMC9072663 DOI: 10.3389/fnagi.2022.861350] [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: 01/24/2022] [Accepted: 03/21/2022] [Indexed: 12/02/2022] Open
Abstract
In this review, the current understanding of leptin’s role in energy balance, glycemic regulation, and cognitive function is examined, and its involvement in maintaining the homeostatic “harmony” of these physiologies is explored. The effects of exercise on circulating leptin levels are summarized, and the results of clinical application of leptin to metabolic disease and neurologic dysfunction are reviewed. Finally, pre-clinical evidence is presented which suggests that synthetic peptide leptin mimetics may be useful in resolving not only the leptin resistance associated with common obesity and other elements of metabolic syndrome, but also the peripheral insulin resistance characterizing type 2 diabetes mellitus, and the central insulin resistance associated with certain neurologic deficits in humans.
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Affiliation(s)
- Patricia Grasso
- Department of Medicine, Albany Medical College, Albany, NY, United States
- Department of Neuroscience and Experimental Therapeutics, Albany Medical College, Albany, NY, United States
- *Correspondence: Patricia Grasso,
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28
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Parvanehvar S, Tehranian N, Kazemnejad A, Mozdarani H, Hedayati M. Maternal serum adiponectin and leptin levels and their gene expression, postpartum body mass index, and breastfeeding duration based on mode of delivery: A prospective study. J Obstet Gynaecol Res 2022; 48:1768-1774. [PMID: 35384157 DOI: 10.1111/jog.15251] [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] [Received: 08/01/2021] [Revised: 02/19/2022] [Accepted: 03/21/2022] [Indexed: 12/27/2022]
Abstract
BACKGROUND Adipokines are involved in inflammatory responses, associated with body mass index whose concentrations may change in response to inflammatory conditions, including surgery and delivery. We examined adiponectin and leptin levels and their gene expression at birth, body mass index, and breastfeeding duration at 24 months postpartum according to mode of delivery. METHODS In this study, 90 normal pregnant women were investigated. Blood samples were collected after delivery. Serum levels and gene expression of adiponectin and leptin were evaluated. Body mass index and breastfeeding duration were calculated at 24 months postpartum. Data were analyzed using SPSS-16 and p < 0.05 was considered as significant. RESULTS Serum leptin level was significantly higher in vaginal delivery than in cesarean section (p = 0.033). No significant difference was found between two groups regarding adiponectin level and gene expression, while leptin gene expression was significantly higher in cesarean (p = 0.005). Postpartum body mass index did not differ between the two groups (p = 0.14). On the other hand, postpartum body mass index was significantly higher than the equivalent prepregnancy index in both groups (p < 0.001) and was associated with serum leptin and adiponectin in vaginal delivery (r = 0.46, p = 0.001, and r = -0.3, p = 0.04, respectively). The duration of breastfeeding was longer in vaginal delivery (p = 0.008). CONCLUSION Cesarean section was associated with lower maternal leptin levels and shorter breast-feeding duration compared to vaginal delivery. Leptin gene expression was significantly higher in cesarean section than in vaginal delivery. Postpartum body mass index, adiponectin level, and gene expression did not differ between the two groups.
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Affiliation(s)
- Simin Parvanehvar
- Department of Reproductive Health and Midwifery, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.,Department of Midwifery, Varamin-Pishva Branch, Islamic Azad University, Varamin, Iran
| | - Najmeh Tehranian
- Department of Reproductive Health and Midwifery, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Anoshirvan Kazemnejad
- Department of Biostatistics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Hossein Mozdarani
- Department of Medical Genetics -Medical Cytogenetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Mehdi Hedayati
- Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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29
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The role of leptin and low testosterone in obesity. Int J Impot Res 2022; 34:704-713. [DOI: 10.1038/s41443-022-00534-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Accepted: 01/21/2022] [Indexed: 12/29/2022]
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30
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Metabolic-endocrine disruption due to preterm birth impacts growth, body composition, and neonatal outcome. Pediatr Res 2022; 91:1350-1360. [PMID: 34040160 PMCID: PMC9197767 DOI: 10.1038/s41390-021-01566-8] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 04/19/2021] [Accepted: 04/22/2021] [Indexed: 02/05/2023]
Abstract
Despite optimized nutrition, preterm-born infants grow slowly and tend to over-accrete body fat. We hypothesize that the premature dissociation of the maternal-placental-fetal unit disrupts the maintenance of physiological endocrine function in the fetus, which has severe consequences for postnatal development. This review highlights the endocrine interactions of the maternal-placental-fetal unit and the early perinatal period in both preterm and term infants. We report on hormonal levels (including tissue, thyroid, adrenal, pancreatic, pituitary, and placental hormones) and nutritional supply and their impact on infant body composition. The data suggest that the premature dissociation of the maternal-placental-fetal unit leads to a clinical picture similar to panhypopituitarism. Further, we describe how the premature withdrawal of the maternal-placental unit, neonatal morbidities, and perinatal stress can cause differences in the levels of growth-promoting hormones, particularly insulin-like growth factors (IGF). In combination with the endocrine disruption that occurs following dissociation of the maternal-placental-fetal unit, the premature adaptation to the extrauterine environment leads to early and fast accretion of fat mass in an immature body. In addition, we report on interventional studies that have aimed to compensate for hormonal deficiencies in infants born preterm through IGF therapy, resulting in improved neonatal morbidity and growth. IMPACT: Preterm birth prematurely dissociates the maternal-placental-fetal unit and disrupts the metabolic-endocrine maintenance of the immature fetus with serious consequences for growth, body composition, and neonatal outcomes. The preterm metabolic-endocrine disruption induces symptoms resembling anterior pituitary failure (panhypopituitarism) with low levels of IGF-1, excessive postnatal fat mass accretion, poor longitudinal growth, and failure to thrive. Appropriate gestational age-adapted nutrition alone seems insufficient for the achievement of optimal growth of preterm infants. Preliminary results from interventional studies show promising effects of early IGF-1 supplementation on postnatal development and neonatal outcomes.
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Gallo M, Adinolfi V, Barucca V, Prinzi N, Renzelli V, Barrea L, Di Giacinto P, Ruggeri RM, Sesti F, Arvat E, Baldelli R, Arvat E, Colao A, Isidori A, Lenzi A, Baldell R, Albertelli M, Attala D, Bianchi A, Di Sarno A, Feola T, Mazziotti G, Nervo A, Pozza C, Puliani G, Razzore P, Ramponi S, Ricciardi S, Rizza L, Rota F, Sbardella E, Zatelli MC. Expected and paradoxical effects of obesity on cancer treatment response. Rev Endocr Metab Disord 2021; 22:681-702. [PMID: 33025385 DOI: 10.1007/s11154-020-09597-y] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/25/2020] [Indexed: 12/12/2022]
Abstract
Obesity, whose prevalence is pandemic and continuing to increase, is a major preventable and modifiable risk factor for diabetes and cardiovascular diseases, as well as for cancer. Furthermore, epidemiological studies have shown that obesity is a negative independent prognostic factor for several oncological outcomes, including overall and cancer-specific survival, for several site-specific cancers as well as for all cancers combined. Yet, a recently growing body of evidence suggests that sometimes overweight and obesity may associate with better outcomes, and that immunotherapy may show improved response among obese patients compared with patients with a normal weight. The so-called 'obesity paradox' has been reported in several advanced cancer as well as in other diseases, albeit the mechanisms behind this unexpected relationship are still not clear. Aim of this review is to explore the expected as well as the paradoxical relationship between obesity and cancer prognosis, with a particular emphasis on the effects of cancer therapies in obese people.
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Affiliation(s)
- Marco Gallo
- Oncological Endocrinology Unit, Department of Medical Sciences, University of Turin, AOU Città della Salute e della Scienza di Torino, Via Genova, 3, 10126, Turin, Italy.
| | - Valerio Adinolfi
- Endocrinology and Diabetology Unit, ASL Verbano Cusio Ossola, Domodossola, Italy
| | - Viola Barucca
- Oncology Unit, Department of Oncology and Medical Specialities, AO San Camillo-Forlanini, Rome, Italy
| | - Natalie Prinzi
- ENETS Center of Excellence, Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori Milano, Milan, Italy
| | - Valerio Renzelli
- Department of Experimental Medicine, AO S. Andrea, Sapienza University of Rome, Rome, Italy
| | - Luigi Barrea
- Endocrinology Unit, Department of Clinical Medicine and Surgery, Federico II University Medical School of Naples, Naples, Italy
| | - Paola Di Giacinto
- Endocrinology Unit, Department of Oncology and Medical Specialities, AO San Camillo-Forlanini, Rome, Italy
| | - Rosaria Maddalena Ruggeri
- Endocrine Unit, Department of Clinical and Experimental Medicine, University of Messina, AOU Policlinico G. Martino, Messina, Italy
| | - Franz Sesti
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | - Emanuela Arvat
- Oncological Endocrinology Unit, Department of Medical Sciences, University of Turin, AOU Città della Salute e della Scienza di Torino, Via Genova, 3, 10126, Turin, Italy
| | - Roberto Baldelli
- Endocrinology Unit, Department of Oncology and Medical Specialities, AO San Camillo-Forlanini, Rome, Italy
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Sun L, Ma H, Gao Y, Wang Z, Cao C. Functional Identification and Characterization of Leucokinin and Its Receptor in the Fall Webworm, Hyphantria cunea. Front Physiol 2021; 12:741362. [PMID: 34690813 PMCID: PMC8529013 DOI: 10.3389/fphys.2021.741362] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Accepted: 09/13/2021] [Indexed: 11/22/2022] Open
Abstract
Neuropeptides function as central neuromodulators and circulating hormones that modulate insect behavior and physiology. Leucokinin (LK) is an intercellular signaling molecule that mediates many physiological and behavioral processes. However, the functions of LK associated with environmental stress and feeding behavior in the fall webworm, Hyphantria cunea, is little known. Our primary objective is to understand the function of LK and LK receptor (LKR) neuroendocrine system in H. cunea. In the present study, the results showed that LK/LKR are expressed at different developmental stages and in various tissues of H. cunea. A candidate receptor-ligand pairing for LK was identified in the larval transcriptome of H. cunea. In a heterologous expression system, the calcium assay was used to demonstrate that LKR is activated by HcLKs in a dose-dependent manner, with 50% effective concentration (EC50) values of 8.44-90.44nM. Knockdown of HcLK and HcLKR by microinjecting target-specific dsRNA leads to several effects in H. cunea, including feeding promotion, increase in resistance to desiccation and starvation stress, and regulation of water homeostasis. The transcript levels of HILP2 (except in the LK knockdown group), HILP5, and HILP8 increased, whereas those of HILP3, HILP4, and HILP6 decreased; HILP1, HILP2 (in the LK knockdown group), and HILP7 gene expression was not influenced after LK and LKR knockdown. Variations in mRNA expression levels in insulin-like peptide genes in the knockdown larvae suggest an essential role of these genes in survival in H. cunea. To our knowledge, the present study is the first comprehensive study of LK and LKR - from gene to behavior - in H. cunea.
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Affiliation(s)
| | | | | | | | - Chuanwang Cao
- Key Laboratory of Sustainable Forest Ecosystem Management-Ministry of Education, College of Forestry, Northeast Forestry University, Harbin, China
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Cinkir U, Bir LS, Topsakal S, Avci Cicek E, Tekin S. Investigation of blood leptin and adropin levels in patients with multiple sclerosis: A CONSORT-clinical study. Medicine (Baltimore) 2021; 100:e27247. [PMID: 34664869 PMCID: PMC8448068 DOI: 10.1097/md.0000000000027247] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2021] [Accepted: 08/27/2021] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND The effects of adipokines have been investigated in multiple sclerosis (MS) in the literature. Results are uncertain, and subgroups like adropin have not been previously studied. We primarily aimed to determine leptin and adropin levels in MS and their potential use as a biomarker. METHODS This study was an experimental research. While 44 MS patients diagnosed according to McDonald criteria were included in the patient group, 40 people without MS diagnosis and risk factors took part in the control group. Demographic data, height, weight, body mass index, blood glucose, thyroid-stimulating hormone, alanine transaminase, aspartate transaminase, creatinine, low-density lipoprotein, leptin, adropin levels, presence of hypertension, diabetes mellitus, coronary artery disease were recorded. Expanded disability status scale and disease duration were also evaluated in the patient group. Our data were presented as mean ± standard deviations. RESULTS The mean blood leptin value of the patient group (6.12 ± 5.34 ng/mL) was significantly lower than the value of the control group (13.02 ± 8.25 ng/mL) (P < .001). The patient group had a mean adropin level of 504.12 ± 311.17 ng/mL, which was significantly lower than that of the control group (747.0 ± 309.42 ng/mL) (P < .001). Statistically insignificant differences were found between their body mass index, glucose, alanine transaminase, aspartate transaminase, thyroid-stimulating hormone, low-density lipoprotein levels (P > .001). CONCLUSION This is the first study that has evaluated adropin levels in patients with MS. The relationship between MS and leptin levels is still unclear. Therefore, our study might be helpful to elucidate MS pathogenesis and provide supportive criteria for diagnosis.
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Affiliation(s)
- Ufuk Cinkir
- Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey
| | | | - Senay Topsakal
- Pamukkale University Faculty of Medicine, Denizli, Turkey
| | | | - Selma Tekin
- Pamukkale University Faculty of Medicine, Denizli, Turkey
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Dalamaga M, Christodoulatos GS, Karampela I, Vallianou N, Apovian CM. Understanding the Co-Epidemic of Obesity and COVID-19: Current Evidence, Comparison with Previous Epidemics, Mechanisms, and Preventive and Therapeutic Perspectives. Curr Obes Rep 2021; 10:214-243. [PMID: 33909265 PMCID: PMC8080486 DOI: 10.1007/s13679-021-00436-y] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/14/2021] [Indexed: 02/06/2023]
Abstract
PURPOSE OF REVIEW A growing body of evidence suggests that obesity and increased visceral adiposity are strongly and independently linked to adverse outcomes and death due to COVID-19. This review summarizes current epidemiologic data, highlights pathogenetic mechanisms on the association between excess body weight and COVID-19, compares data from previous pandemics, discusses why COVID-19 challenges the "obesity paradox," and presents implications in prevention and treatment as well as future perspectives. RECENT FINDINGS Data from meta-analyses based on recent observational studies have indicated that obesity increases the risks of infection from SARS-CoV-2, severe infection and hospitalization, admission to the ICU and need of invasive mechanical ventilation (IMV), and the risk of mortality, particularly in severe obesity. The risks of IMV and mortality associated with obesity are accentuated in younger individuals (age ≤ 50 years old). The meta-inflammation in obesity intersects with and exacerbates underlying pathogenetic mechanisms in COVID-19 through the following mechanisms and factors: (i) impaired innate and adaptive immune responses; (ii) chronic inflammation and oxidative stress; (iii) endothelial dysfunction, hypercoagulability, and aberrant activation of the complement; (iv) overactivation of the renin-angiotensin-aldosterone system; (v) overexpression of the angiotensin-converting enzyme 2 receptor in the adipose tissue; (vi) associated cardiometabolic comorbidities; (vii) vitamin D deficiency; (viii) gut dysbiosis; and (ix) mechanical and psychological issues. Mechanistic and large epidemiologic studies using big data sources with omics data exploring genetic determinants of risk and disease severity as well as large randomized controlled trials (RCTs) are necessary to shed light on the pathways connecting chronic subclinical inflammation/meta-inflammation with adverse COVID-19 outcomes and establish the ideal preventive and therapeutic approaches for patients with obesity.
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Affiliation(s)
- Maria Dalamaga
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Mikras Asias 75, Goudi, 11527 Athens, Greece
| | - Gerasimos Socrates Christodoulatos
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Mikras Asias 75, Goudi, 11527 Athens, Greece
| | - Irene Karampela
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Mikras Asias 75, Goudi, 11527 Athens, Greece
- Second Department of Critical Care, Attikon General University Hospital, Medical School, National and Kapodistrian University of Athens, 1 Rimini St, Haidari, 12462 Athens, Greece
| | - Natalia Vallianou
- Department of Internal Medicine and Endocrinology, Evangelismos General Hospital of Athens, 45-47 Ypsilantou street, 10676 Athens, Greece
| | - Caroline M. Apovian
- Section of Endocrinology, Diabetes, Nutrition, and Weight Management, Department of Medicine, Boston University School of Medicine and Boston Medical Center, Doctor’s Office Building, 720 Harrison Avenue, Suite, Boston, MA 8100 USA
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Seasonal and Nutritional Fluctuations in the mRNA Levels of the Short Form of the Leptin Receptor ( LRa) in the Hypothalamus and Anterior Pituitary in Resistin-Treated Sheep. Animals (Basel) 2021; 11:ani11082451. [PMID: 34438908 PMCID: PMC8388769 DOI: 10.3390/ani11082451] [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: 07/15/2021] [Revised: 08/13/2021] [Accepted: 08/18/2021] [Indexed: 12/13/2022] Open
Abstract
Simple Summary Research since the discovery of leptin has mainly focused on the long form of the leptin receptor. Currently, experiments on the short form of the leptin receptor have confirmed that not only is short form of leptin receptor present in the hypothalamus, but also expanded knowledge with information documenting the specific expression of that form of leptin receptor in selected areas of the hypothalamus and in the pituitary gland. In addition, we have shown that short form of leptin receptor expression levels are affected by day length, adiposity and resistin in sheep. Abstract The short form of the leptin receptor (LRa) plays a key role in the transport of leptin to the central nervous system (CNS). Here, the resistin (RSTN)-mediated expression of LRa in the preoptic area (POA), ventromedial and dorsomedial nuclei (VMH/DMH),arcuate nucleus (ARC) and the anterior pituitary gland (AP)was analyzed considering the photoperiodic (experiment 1) and nutritional status (experiment 2) of ewes. In experiment 1, 30 sheep were fed normally and received one injection of saline or two doses of RSTN one hour prior to euthanasia. RSTN increased LRa expression mainly in the ARC and AP during long days (LD) and only in the AP during short days (SD). In experiment 2, an altered diet for 5 months created lean or fat sheep. Twenty sheep were divided into four groups: the lean and fat groups were given saline, while the lean-R and fat-R groups received RSTN one hour prior to euthanasia. Changes in adiposity influenced the effect of RSTN on LRa mRNA transcript levels in the POA, ARC and AP and without detection of LRa in the VMH/DMH. Overall, both photoperiodic and nutritional signals influence the effects of RSTN on leptin transport to the CNS and are involved in the adaptive/pathological phenomenon of leptin resistance in sheep.
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Karampela I, Chrysanthopoulou E, Skyllas G, Christodoulatos GS, Kandri E, Antonakos G, Stratigou T, Armaganidis A, Dalamaga M. Circulating leptin, soluble leptin receptor and free leptin index in critically ill patients with sepsis: a prospective observational study. Minerva Anestesiol 2021; 87:880-890. [PMID: 34102805 DOI: 10.23736/s0375-9393.21.15368-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
BACKGROUND Leptin, the prototype adipokine, exerts immunomodulatory actions being implicated in inflammatory responses during sepsis. Clinical evidence regarding its role in sepsis has been contradictory, while free leptin has not been studied. Our aim was to jointly investigate circulating total leptin, its soluble receptor (sOBR), and free leptin, as well as their kinetics in critically ill patients with sepsis regarding their diagnostic and prognostic value. METHODS In a prospective study, serum total leptin, sOBR and free leptin index (FLI) were determined in 102 critically ill patients with sepsis within 48 hours from sepsis onset and one week after enrollment, and in 102 age and gender-matched healthy controls. RESULTS Upon enrollment, total leptin, sOB-R and FLI were significantly higher in septic patients compared to controls and they were positively correlated with sepsis severity scores, while they presented a significant decrease during the first week (p<0.001). The decrease in total leptin and sOB-R was significantly higher in patients with sepsis compared to septic shock and in survivors compared to nonsurvivors at 28 days (p<0.001). Higher serum total leptin was independently associated with survival at 28 days (enrollment: HR 0.86, p=0.03; one week after: HR 0.77, p<0.001). Higher kinetics of total leptin (but not FLI) was independently associated with survival after adjustment (HR: 0.48, p=0.001). CONCLUSIONS Higher circulating total leptin and its higher kinetics during the first week from sepsis onset independently predict 28 day survival in critically ill patients. Free leptin did not present any additional diagnostic and prognostic value in sepsis.
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Affiliation(s)
- Irene Karampela
- Second Department of Critical Care, Attikon General University Hospital, Medical School, National and Kapodistrian University of Athens, Haidari, Greece -
| | - Evangelia Chrysanthopoulou
- Second Department of Critical Care, Attikon General University Hospital, Medical School, National and Kapodistrian University of Athens, Haidari, Greece
| | - George Skyllas
- Second Department of Critical Care, Attikon General University Hospital, Medical School, National and Kapodistrian University of Athens, Haidari, Greece
| | | | - Evangelia Kandri
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Georgios Antonakos
- Laboratory of Clinical Biochemistry, Attikon General University Hospital, Medical School, National and Kapodistrian University of Athens, Haidari, Greece
| | - Theodora Stratigou
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Apostolos Armaganidis
- Second Department of Critical Care, Attikon General University Hospital, Medical School, National and Kapodistrian University of Athens, Haidari, Greece
| | - Maria Dalamaga
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece
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Karampela I, Sakelliou A, Vallianou N, Christodoulatos GS, Magkos F, Dalamaga M. Vitamin D and Obesity: Current Evidence and Controversies. Curr Obes Rep 2021; 10:162-180. [PMID: 33792853 DOI: 10.1007/s13679-021-00433-1] [Citation(s) in RCA: 89] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/11/2021] [Indexed: 12/12/2022]
Abstract
PURPOSE OF REVIEW Evidence from observational studies suggests that obesity is associated with low vitamin D. As both obesity and hypovitaminosis D present an alarmingly increased prevalence worldwide, there is an intense research interest to clarify all aspects of this association. This review summarizes current evidence from meta-analyses investigating vitamin D status in obesity, including the effects of weight loss and bariatric surgery on vitamin D status and the outcomes of vitamin D supplementation on body weight. We also discuss potential pathophysiologic mechanisms and important controversies. RECENT FINDINGS Data from meta-analyses consistently support an inverse association of vitamin D levels with body weight. However, the impact of weight loss on improving vitamin D status is small, while studies on the supplementation with vitamin D after bariatric surgery have shown conflicting results regarding vitamin D status. Moreover, interventional studies do not support a beneficial effect of vitamin D supplementation on body weight. These findings warrant a cautious interpretation due to important methodological limitations and confounding factors, such as high heterogeneity of studies, variable methods of determination of vitamin D and definition of deficiency/insufficiency, use of various adiposity measures and definitions of obesity, and inadequate adjustment for confounding variables influencing vitamin D levels. The underlying pathogenetic mechanisms associating low vitamin D in obesity include volumetric dilution, sequestration into adipose tissue, limited sunlight exposure, and decreased vitamin D synthesis in the adipose tissue and liver. Experimental studies have demonstrated that low vitamin D may be implicated in adipose tissue differentiation and growth leading to obesity either by regulation of gene expression or through modulation of parathyroid hormone, calcium, and leptin. Obesity is associated with low vitamin D status but weight loss has little effect on improving this; vitamin D supplementation is also not associated with weight loss. Evidence regarding vitamin D status after bariatric surgery is contradicting. The link between vitamin D and obesity remains controversial due to important limitations and confounding of studies. More research is needed to clarify the complex interplay between vitamin D and adiposity.
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Affiliation(s)
- Irene Karampela
- Second Department of Critical Care, Medical School, Attikon General University Hospital, National and Kapodistrian University of Athens, 1 Rimini St, Haidari, 12462, Athens, Greece.
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Mikras Asias 75, Goudi, 11527, Athens, Greece.
| | - Alexandra Sakelliou
- Second Department of Critical Care, Medical School, Attikon General University Hospital, National and Kapodistrian University of Athens, 1 Rimini St, Haidari, 12462, Athens, Greece
| | - Natalia Vallianou
- First Department of Internal Medicine, Evangelismos General Hospital, 45-47 Ypsilantou St, 10676, Athens, Greece
| | - Gerasimos-Socrates Christodoulatos
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Mikras Asias 75, Goudi, 11527, Athens, Greece
| | - Faidon Magkos
- Department of Nutrition, Exercise, and Sports, University of Copenhagen, Copenhagen, Denmark
| | - Maria Dalamaga
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Mikras Asias 75, Goudi, 11527, Athens, Greece
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Endocrine role of bone in the regulation of energy metabolism. Bone Res 2021; 9:25. [PMID: 34016950 PMCID: PMC8137703 DOI: 10.1038/s41413-021-00142-4] [Citation(s) in RCA: 71] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2020] [Revised: 12/20/2020] [Accepted: 01/12/2021] [Indexed: 02/06/2023] Open
Abstract
Bone mainly functions as a supportive framework for the whole body and is the major regulator of calcium homeostasis and hematopoietic function. Recently, an increasing number of studies have characterized the significance of bone as an endocrine organ, suggesting that bone-derived factors regulate local bone metabolism and metabolic functions. In addition, these factors can regulate global energy homeostasis by altering insulin sensitivity, feeding behavior, and adipocyte commitment. These findings may provide a new pathological mechanism for related metabolic diseases or be used in the diagnosis, treatment, and prevention of metabolic diseases such as osteoporosis, obesity, and diabetes mellitus. In this review, we summarize the regulatory effect of bone and bone-derived factors on energy metabolism and discuss directions for future research.
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The Causes and Potential Injurious Effects of Elevated Serum Leptin Levels in Chronic Kidney Disease Patients. Int J Mol Sci 2021; 22:ijms22094685. [PMID: 33925217 PMCID: PMC8125133 DOI: 10.3390/ijms22094685] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 04/25/2021] [Accepted: 04/27/2021] [Indexed: 12/15/2022] Open
Abstract
Leptin is an adipokine that regulates appetite and body mass and has many other pleiotropic functions, including regulating kidney function. Increased evidence shows that chronic kidney disease (CKD) is associated with hyperleptinemia, but the reasons for this phenomenon are not fully understood. In this review, we focused on potential causes of hyperleptinemia in patients with CKD and the effects of elevated serum leptin levels on patient kidney function and cardiovascular risk. The available data indicate that the increased concentration of leptin in the blood of CKD patients may result from both decreased leptin elimination from the circulation by the kidneys (due to renal dysfunction) and increased leptin production by the adipose tissue. The overproduction of leptin by the adipose tissue could result from: (a) hyperinsulinemia; (b) chronic inflammation; and (c) significant lipid disturbances in CKD patients. Elevated leptin in CKD patients may further deteriorate kidney function and lead to increased cardiovascular risk.
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Role of Insulin Resistance in MAFLD. Int J Mol Sci 2021; 22:ijms22084156. [PMID: 33923817 PMCID: PMC8072900 DOI: 10.3390/ijms22084156] [Citation(s) in RCA: 228] [Impact Index Per Article: 57.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Accepted: 04/14/2021] [Indexed: 12/17/2022] Open
Abstract
Many studies have reported that metabolic dysfunction is closely involved in the complex mechanism underlying the development of non-alcoholic fatty liver disease (NAFLD), which has prompted a movement to consider renaming NAFLD as metabolic dysfunction-associated fatty liver disease (MAFLD). Metabolic dysfunction in this context encompasses obesity, type 2 diabetes mellitus, hypertension, dyslipidemia, and metabolic syndrome, with insulin resistance as the common underlying pathophysiology. Imbalance between energy intake and expenditure results in insulin resistance in various tissues and alteration of the gut microbiota, resulting in fat accumulation in the liver. The role of genetics has also been revealed in hepatic fat accumulation and fibrosis. In the process of fat accumulation in the liver, intracellular damage as well as hepatic insulin resistance further potentiates inflammation, fibrosis, and carcinogenesis. Increased lipogenic substrate supply from other tissues, hepatic zonation of Irs1, and other factors, including ER stress, play crucial roles in increased hepatic de novo lipogenesis in MAFLD with hepatic insulin resistance. Herein, we provide an overview of the factors contributing to and the role of systemic and local insulin resistance in the development and progression of MAFLD.
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Kim Y, Hersch J, Bodell LP, Schebendach J, Hildebrandt T, Walsh BT, Mayer LES. The association between leptin and weight maintenance outcome in anorexia nervosa. Int J Eat Disord 2021; 54:527-534. [PMID: 33185933 PMCID: PMC9851598 DOI: 10.1002/eat.23407] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Revised: 10/14/2020] [Accepted: 10/28/2020] [Indexed: 01/21/2023]
Abstract
OBJECTIVE Relapse after weight restoration in anorexia nervosa (AN) is a critical problem. Higher body fat percentage after weight gain has been shown to predict better weight maintenance outcome. Leptin, a fat-derived hormone, has been associated with progress during weight gain, but its association with weight maintenance is unknown. This study aims to determine whether leptin levels after weight restoration in AN are associated with weight maintenance. METHOD Participants were 41 women with AN hospitalized for inpatient treatment. Participants were evaluated 2-4 weeks after weight restoration to body mass index (BMI) ≥ 19.5 kg/m2 for plasma leptin and body composition. Weight maintenance outcome was defined by whether a participant maintained a BMI of at least 18.5 kg/m2 at the end of 1 year following hospital discharge. RESULTS Twenty (48.8%) out of 41 patients maintained their weight at 1 year. Percent body fat and leptin were significantly higher in the group who maintained weight (body fat, p = .004, Hedges' g = 0.944; log-leptin, p = .010, Hedges' g = 0.821), but there were no differences in predischarge BMI, duration of illness, and duration of amenorrhea. Using regression modeling, only higher log-leptin (pWald = .021) and percent body fat (pWald = .010), as well as fat-adjusted leptin (pWald = .029), independently predicted weight maintenance at 1 year. DISCUSSIONS Our findings suggest that for acutely-weight restored women with AN, higher predischarge leptin measurements are associated with better outcome in the year following treatment. Prospective studies examining leptin as well as other parameters of metabolic health could offer insights into biomarkers that may improve clinical outcomes.
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Affiliation(s)
- Youngjung Kim
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai Hospital, New York, New York
| | | | - Lindsay P. Bodell
- Department of Psychology, University of Western Ontario, London, Ontario, Canada
| | - Janet Schebendach
- Department of Psychiatry, Columbia University Irving Medical Center and the New York State Psychiatric Institute, New York, New York
| | - Tom Hildebrandt
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai Hospital, New York, New York
| | - B. Timothy Walsh
- Department of Psychiatry, Columbia University Irving Medical Center and the New York State Psychiatric Institute, New York, New York
| | - Laurel E. S. Mayer
- Department of Psychiatry, Columbia University Irving Medical Center and the New York State Psychiatric Institute, New York, New York
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Ramskov Tetzlaff CN, Ramhøj L, Lardenois A, Axelstad M, Evrard B, Chalmel F, Taxvig C, Svingen T. Adult female rats perinatally exposed to perfluorohexane sulfonate (PFHxS) and a mixture of endocrine disruptors display increased body/fat weights without a transcriptional footprint in fat cells. Toxicol Lett 2021; 339:78-87. [DOI: 10.1016/j.toxlet.2020.12.018] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Revised: 12/22/2020] [Accepted: 12/26/2020] [Indexed: 12/11/2022]
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Cook K, Adamski K, Gomes A, Tuttle E, Kalden H, Cochran E, Brown RJ. Effects of Metreleptin on Patient Outcomes and Quality of Life in Generalized and Partial Lipodystrophy. J Endocr Soc 2021; 5:bvab019. [PMID: 33817539 DOI: 10.1210/jendso/bvab019] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Indexed: 02/08/2023] Open
Abstract
Generalized and partial lipodystrophy are rare and complex diseases with progressive clinical and humanistic burdens stemming from selective absence of subcutaneous adipose tissue, which causes reduced energy storage capacity and a deficiency of adipokines such as leptin. Treatment options were limited before leptin replacement therapy (metreleptin) became available. This retrospective study evaluates both clinical and humanistic consequences of the disease and treatment. Chart data were abstracted from a cohort of metreleptin-treated patients with generalized and partial lipodystrophy (n = 112) treated at the US National Institutes of Health. To quantify the quality-of-life consequences of the lipodystrophy disease attributes recorded in chart data, a discrete choice experiment was completed in 6 countries (US, n = 250; EU, n = 750). Resulting utility decrements were used to estimate the quality-adjusted life-year consequences of changes in lipodystrophy attribute prevalence before and after metreleptin. In addition to metabolic impairment, patients with generalized and partial lipodystrophy experienced a range of lipodystrophy consequences, including liver abnormality (94%), hyperphagia (79%), impaired physical appearance (77%), kidney abnormality (63%), reproductive dysfunction (80% of females of reproductive age), and pancreatitis (39%). Improvement was observed in these attributes following initiation of metreleptin. Quality-adjusted life-year gains associated with 12 months of treatment with metreleptin were estimated at 0.313 for generalized and 0.117 for partial lipodystrophy, reducing the gap in quality of life between untreated lipodystrophy and perfect health by approximately 59% and 31%, respectively. This study demonstrates that metreleptin is associated with meaningful clinical and quality-of-life improvements.
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Affiliation(s)
- Keziah Cook
- Analysis Group, Inc., Menlo Park, CA 94025, USA
| | | | | | | | - Henner Kalden
- Amryt Pharmaceuticals DAC, 45 Mespil Road, Dublin 8QM2+6R, Ireland
| | - Elaine Cochran
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
| | - Rebecca J Brown
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
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Lesser Investigated Natural Ingredients for the Management of Obesity. Nutrients 2021; 13:nu13020510. [PMID: 33557185 PMCID: PMC7913945 DOI: 10.3390/nu13020510] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 01/30/2021] [Accepted: 01/31/2021] [Indexed: 12/13/2022] Open
Abstract
Obesity, an epidemiological disorder, is related to various complications in both the developed and developing world. It epitomizes a crucial risk factor for health, decreasing productivity and life expectancy while increasing health care costs worldwide. Conventional therapies with synthetic drugs or bariatric surgery, associated with numerous side effects, recurrence, and surgical complexity, have been restricted in their use. Lifestyle changes and dietary restrictions are the proven methods for successful weight loss, although maintaining a strict lifestyle is a challenge. Multiple natural products have been explored for weight management with varied efficacy. The current review explores less explored natural herbs, their active constituents, and their mechanisms of action against obesity.
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Tsigalou C, Paraschaki A, Karvelas A, Kantartzi K, Gagali K, Tsairidis D, Bezirtzoglou E. Gut microbiome and Mediterranean diet in the context of obesity. Current knowledge, perspectives and potential therapeutic targets. Metabol Open 2021; 9:100081. [PMID: 33644741 PMCID: PMC7892986 DOI: 10.1016/j.metop.2021.100081] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2020] [Revised: 01/14/2021] [Accepted: 01/19/2021] [Indexed: 02/06/2023] Open
Abstract
Mediterranean Diet has been recognized as one of the healthiest and sustainable dietary patterns worldwide, based on the food habits of people living in the Mediterranean region. It is focused on a plant-based cuisine combining local agricultural products and moderate intake of fish. As eating habits seem to exert a major impact on the composition of gut microbiota, numerous studies show that an adherence to the Mediterranean diet positively influences the microbiome ecosystem network. This has a profound effect on multiple host metabolic pathways and plays a major role in immune and metabolic homeostasis. Among metabolic disorders, obesity represents a major health issue where Mediterranean Dietary regime could possibly slowdown its spread. The aim of this review is to emphasize the interaction between diet and gut microbiota and the potential beneficial effects of Mediterranean diet on metabolic disorders like obesity, which is responsible for the development of many noncommunicable diseases.
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Affiliation(s)
- Christina Tsigalou
- Laboratory of Microbiology, School of Medicine, Democritus University of Thrace, University General Hospital of Alexandroupolis, Dragana Campus, Alexandroupolis, 68100, Greece
| | - Afroditi Paraschaki
- Laboratory of Microbiology, School of Medicine, Democritus University of Thrace, University General Hospital of Alexandroupolis, Dragana Campus, Alexandroupolis, 68100, Greece
| | - Alexandros Karvelas
- Laboratory of Microbiology, School of Medicine, Democritus University of Thrace, University General Hospital of Alexandroupolis, Dragana Campus, Alexandroupolis, 68100, Greece
| | - Konstantina Kantartzi
- Department of Nephrology, Democritus University of Thrace, University General Hospital of Alexandroupolis Dragana Campus, Alexandroupolis, 68100, Greece
| | - Kenan Gagali
- University General Hospital of Alexandroupolis, Dragana Campus, Alexandroupolis, 68100, Greece
| | - Dimitrios Tsairidis
- Laboratory of Hygiene and Environmental Protection, Medical School, Democritus University of Thrace, Dragana, Alexandroupolis, 68100, Greece
| | - Eugenia Bezirtzoglou
- Laboratory of Hygiene and Environmental Protection, Medical School, Democritus University of Thrace, Dragana, Alexandroupolis, 68100, Greece
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Tolle V, Ramoz N, Epelbaum J. Is there a hypothalamic basis for anorexia nervosa? HANDBOOK OF CLINICAL NEUROLOGY 2021; 181:405-424. [PMID: 34238474 DOI: 10.1016/b978-0-12-820683-6.00030-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
The hypothalamus has long been known to control food intake and energy metabolism through a complex network of primary and secondary neurons and glial cells. Anorexia nervosa being a complex disorder characterized by abnormal feeding behavior and food aversion, it is thus quite surprising that not much is known concerning potential hypothalamic modifications in this disorder. In this chapter, we review the recent advances in the fields of genetics, epigenetics, structural and functional imaging, and brain connectivity, as well as neuroendocrine findings and emerging animal models, which have begun to unravel the importance of hypothalamic adaptive processes to our understanding of the pathology of eating disorders.
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Zonneveld MH, Noordam R, van der Grond J, van Heemst D, Mooijaart SP, Sabayan B, Jukema JW, Trompet S. Interplay of circulating leptin and obesity in cognition and cerebral volumes in older adults. Peptides 2021; 135:170424. [PMID: 33058961 DOI: 10.1016/j.peptides.2020.170424] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Revised: 09/16/2020] [Accepted: 10/08/2020] [Indexed: 10/23/2022]
Abstract
We aimed to investigate whether circulating leptin and body mass index (BMI) associate independently with cognitive function (decline) and brain volumes using magnetic resonance imaging (MRI) in older individuals at risk of cardiovascular disease. We studied the cross-sectional and longitudinal associations in participants enrolled in the PROSPER study (Prospective Study of Pravastatin in the Elderly at Risk). Cognitive function was tested at baseline and repeated during a mean follow-up time of 3.2 years. Analyses were performed with multivariable (repeated) linear regression models and adjusted for demographics, cardiovascular risk-factors, and stratified by sex. We included 5623 dementia-free participants (52 % female, mean age 75 years) with a mean BMI of 26.9 (SD = 4.1). In a sub-study, 527 participants underwent brain MRI. At baseline, individuals with a BMI > 30 had a worse performance on the Stroop test (β 5.0 s, 95 %CI 2.6;7.5) and larger volumes of the amygdala (β 234 mm3, 95 %CI 3;464) and hippocampus (β 590 mm3, 95 %CI 181;999), independent of intracranial volume and serum leptin levels, compared with individuals with the reference BMI (BMI 18-25 kg/m2). Per log ng/mL higher serum leptin, independent of BMI, a 135 mm3 (95 %CI 2;268) higher volume of the amygdala was found, but no association was observed with cognitive tests nor with other brain volumes. Stratification for sex did not materially change the results. Whereas higher BMI associated with worse cognitive function independent of leptin levels, our study provided evidence that leptin and BMI independently associate with amygdala volume suggesting potential distinct biological associations.
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Affiliation(s)
- M H Zonneveld
- Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
| | - R Noordam
- Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
| | - J van der Grond
- Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
| | - D van Heemst
- Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
| | - S P Mooijaart
- Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
| | - B Sabayan
- Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, United States.
| | - J W Jukema
- Department of Cardiology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands; Netherlands Heart Institute, 3511 EP Utrecht, the Netherlands.
| | - S Trompet
- Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
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48
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Conde SV, Sacramento JF, Martins FO. Immunity and the carotid body: implications for metabolic diseases. Bioelectron Med 2020; 6:24. [PMID: 33353562 PMCID: PMC7756955 DOI: 10.1186/s42234-020-00061-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Accepted: 11/24/2020] [Indexed: 12/14/2022] Open
Abstract
Neuro-immune communication has gained enormous interest in recent years due to increasing knowledge of the way in which the brain coordinates functional alterations in inflammatory and autoimmune responses, and the mechanisms of neuron-immune cell interactions in the context of metabolic diseases such as obesity and type 2 diabetes. In this review, we will explain how this relationship between the nervous and immune system impacts the pro- and anti-inflammatory pathways with specific reference to the hypothalamus-pituitary-adrenal gland axis and the vagal reflex and will explore the possible involvement of the carotid body (CB) in the neural control of inflammation. We will also highlight the mechanisms of vagal anti-inflammatory reflex control of immunity and metabolism, and the consequences of functional disarrangement of this reflex in settlement and development of metabolic diseases, with special attention to obesity and type 2 diabetes. Additionally, the role of CB in the interplay between metabolism and immune responses will be discussed, with specific reference to the different stimuli that promote CB activation and the balance between sympathetic and parasympathetic in this context. In doing so, we clarify the multivarious neuronal reflexes that coordinate tissue-specific responses (gut, pancreas, adipose tissue and liver) critical to metabolic control, and metabolic disease settlement and development. In the final section, we will summarize how electrical modulation of the carotid sinus nerve may be utilized to adjust these reflex responses and thus control inflammation and metabolic diseases, envisioning new therapeutics horizons.
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Affiliation(s)
- Silvia V Conde
- iNOVA4Health, CEDOC, NOVA Medical School, NMS, Universidade Nova de Lisboa, Rua Câmara Pestana, n°6, Edifício 2, piso 3, 1150-274, Lisbon, Portugal.
| | - Joana F Sacramento
- iNOVA4Health, CEDOC, NOVA Medical School, NMS, Universidade Nova de Lisboa, Rua Câmara Pestana, n°6, Edifício 2, piso 3, 1150-274, Lisbon, Portugal
| | - Fatima O Martins
- iNOVA4Health, CEDOC, NOVA Medical School, NMS, Universidade Nova de Lisboa, Rua Câmara Pestana, n°6, Edifício 2, piso 3, 1150-274, Lisbon, Portugal
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49
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Unraveling the Role of Leptin in Liver Function and Its Relationship with Liver Diseases. Int J Mol Sci 2020; 21:ijms21249368. [PMID: 33316927 PMCID: PMC7764544 DOI: 10.3390/ijms21249368] [Citation(s) in RCA: 68] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Revised: 11/19/2020] [Accepted: 12/04/2020] [Indexed: 02/06/2023] Open
Abstract
Since its discovery twenty-five years ago, the fat-derived hormone leptin has provided a revolutionary framework for studying the physiological role of adipose tissue as an endocrine organ. Leptin exerts pleiotropic effects on many metabolic pathways and is tightly connected with the liver, the major player in systemic metabolism. As a consequence, understanding the metabolic and hormonal interplay between the liver and adipose tissue could provide us with new therapeutic targets for some chronic liver diseases, an increasing problem worldwide. In this review, we assess relevant literature regarding the main metabolic effects of leptin on the liver, by direct regulation or through the central nervous system (CNS). We draw special attention to the contribution of leptin to the non-alcoholic fatty liver disease (NAFLD) pathogenesis and its progression to more advanced stages of the disease as non-alcoholic steatohepatitis (NASH). Likewise, we describe the contribution of leptin to the liver regeneration process after partial hepatectomy, the mainstay of treatment for certain hepatic malignant tumors.
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50
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Li X, Wang H. Multiple organs involved in the pathogenesis of non-alcoholic fatty liver disease. Cell Biosci 2020; 10:140. [PMID: 33372630 PMCID: PMC7720519 DOI: 10.1186/s13578-020-00507-y] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Accepted: 11/27/2020] [Indexed: 02/08/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) represents the leading cause of chronic liver disease worldwide and the anticipated health burden is huge. There are limited therapeutic approaches for NAFLD now. It’s imperative to get a better understanding of the disease pathogenesis if new treatments are to be discovered. As the hepatic manifestation of metabolic syndrome, this disease involves complex interactions between different organs and regulatory pathways. It’s increasingly clear that brain, gut and adipose tissue all contribute to NAFLD pathogenesis and development, in view of their roles in energy homeostasis. In the present review, we try to summarize currently available data regarding NAFLD pathogenesis and to lay a particular emphasis on the inter-organ crosstalk evidence.
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Affiliation(s)
- Xiaoyan Li
- Department of Oncology, the First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China
| | - Hua Wang
- Department of Oncology, the First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China. .,Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, 230032, China.
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