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Vaughn SA, Berghaus LJ, Hart KA. Assessing the effects of ex vivo hormonal exposure on oxidative responses in equine leukocytes: A preliminary study. Vet Immunol Immunopathol 2024; 276:110827. [PMID: 39293133 DOI: 10.1016/j.vetimm.2024.110827] [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: 05/10/2024] [Revised: 08/24/2024] [Accepted: 09/04/2024] [Indexed: 09/20/2024]
Abstract
Breed differences exist between horses and ponies in circulating concentrations of several hormones, notably ACTH and insulin. These hormones regulate stress and metabolic responses, but in other species, they also impact leukocyte oxidant responses. The effects of these hormones on equine leukocytes have not been evaluated to date. If equine leukocytes are similarly regulated, breed differences in increased plasma hormone concentrations or altered sensitivity to them at the leukocyte level could result in breed-related differences in oxidant responses or oxidative status. The objective of this study was therefore to determine the effects of ex vivo exposure to adrenocorticotropic hormone (ACTH), α-melanocyte stimulating hormone (α-MSH), insulin, or leptin on reactive oxygen species (ROS) production from leukocytes isolated from horses and ponies. We hypothesized that ACTH, α-MSH, insulin, and leptin would alter oxidant responses from equine leukocytes in a breed specific manner. Blood was collected from 10 apparently healthy Quarter horses and seven Welsh ponies for isolation of neutrophils and peripheral blood mononuclear cells (PBMCs) via density gradient centrifugation. Cells were incubated with media (negative control), microbial antigens (positive control), or ACTH, α-MSH, leptin, or insulin for two hours. Induced ROS production was quantified with a previously validated fluorometric assay. Data was compared within groups by comparing a stimulant within a group (horses or ponies) to baseline, between groups by comparing horse response to pony response, and among stimulants using one- and two-way, repeated measures ANOVA (P<0.05). There was no significant effect of breed on basal, microbial-induced, or hormone-induced ROS production from neutrophils (P=0.465) or PBMCs (P=0.749), but in neutrophils, a significant interaction between breed and stimulant was present (P=0.037). ROS production from PBMCs from horses after hormone exposure did not differ from cells exposed to media only (P=0.1520-0.8180). Similarly, neither leptin nor insulin exposure significantly induced ROS production from PBMCs from ponies (P= 0.2645 and 0.4678 respectively), but exposure to ACTH or α-MSH induced a significant increase in ROS production (P=0.0441 and 0.0440 respectively) compared to unstimulated cells. Hormones that vary in availability among breeds may induce ex vivo pro-oxidant responses in equine leukocytes, but specific effects are breed-, leukocyte type-, and hormone-dependent. Breed differences in hormonally induced leukocyte ROS production may warrant further investigation in the context of circulating oxidative stress and how this might relate to future disease risk.
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Affiliation(s)
- Sarah A Vaughn
- Department of Large Animal Medicine, University of Georgia College of Veterinary Medicine, Athens, GA, USA.
| | - Londa J Berghaus
- Department of Large Animal Medicine, University of Georgia College of Veterinary Medicine, Athens, GA, USA
| | - Kelsey A Hart
- Department of Large Animal Medicine, University of Georgia College of Veterinary Medicine, Athens, GA, USA.
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Savulescu-Fiedler I, Mihalcea R, Dragosloveanu S, Scheau C, Baz RO, Caruntu A, Scheau AE, Caruntu C, Benea SN. The Interplay between Obesity and Inflammation. Life (Basel) 2024; 14:856. [PMID: 39063610 PMCID: PMC11277997 DOI: 10.3390/life14070856] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Revised: 07/01/2024] [Accepted: 07/05/2024] [Indexed: 07/28/2024] Open
Abstract
Obesity is an important condition affecting the quality of life of numerous patients and increasing their associated risk for multiple diseases, including tumors and immune-mediated disorders. Inflammation appears to play a major role in the development of obesity and represents a central point for the activity of cellular and humoral components in the adipose tissue. Macrophages play a key role as the main cellular component of the adipose tissue regulating the chronic inflammation and modulating the secretion and differentiation of various pro- and anti-inflammatory cytokines. Inflammation also involves a series of signaling pathways that might represent the focus for new therapies and interventions. Weight loss is essential in decreasing cardiometabolic risks and the degree of associated inflammation; however, the latter can persist for long after the excess weight is lost, and can involve changes in macrophage phenotypes that can ensure the metabolic adjustment. A clear understanding of the pathophysiological processes in the adipose tissue and the interplay between obesity and chronic inflammation can lead to a better understanding of the development of comorbidities and may ensure future targets for the treatment of obesity.
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Affiliation(s)
- Ilinca Savulescu-Fiedler
- Department of Internal Medicine, The “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Department of Internal Medicine and Cardiology, Coltea Clinical Hospital, 030167 Bucharest, Romania
| | - Razvan Mihalcea
- Department of Internal Medicine and Cardiology, Coltea Clinical Hospital, 030167 Bucharest, Romania
| | - Serban Dragosloveanu
- Department of Orthopaedics, “Foisor” Clinical Hospital of Orthopaedics, Traumatology and Osteoarticular TB, 021382 Bucharest, Romania
- Department of Orthopaedics and Traumatology, The “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Cristian Scheau
- Department of Physiology, The “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania (C.C.)
- Department of Radiology and Medical Imaging, “Foisor” Clinical Hospital of Orthopaedics, Traumatology and Osteoarticular TB, 030167 Bucharest, Romania
| | - Radu Octavian Baz
- Clinical Laboratory of Radiology and Medical Imaging, “Sf. Apostol Andrei” County Emergency Hospital, 900591 Constanta, Romania
- Department of Radiology and Medical Imaging, Faculty of Medicine, “Ovidius” University, 900527 Constanta, Romania
| | - Ana Caruntu
- Department of Oral and Maxillofacial Surgery, “Carol Davila” Central Military Emergency Hospital, 010825 Bucharest, Romania
- Department of Oral and Maxillofacial Surgery, Faculty of Dental Medicine, “Titu Maiorescu” University, 031593 Bucharest, Romania
| | - Andreea-Elena Scheau
- Department of Radiology and Medical Imaging, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Constantin Caruntu
- Department of Physiology, The “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania (C.C.)
- Department of Dermatology, “Prof. N.C. Paulescu” National Institute of Diabetes, Nutrition and Metabolic Diseases, 011233 Bucharest, Romania
| | - Serban Nicolae Benea
- Department of Infectious Diseases, The “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
- “Prof. Dr. Matei Balș” National Institute for Infectious Diseases, 021105 Bucharest, Romania
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Olejnik AE, Kuźnar-Kamińska B. Association of Obesity and Severe Asthma in Adults. J Clin Med 2024; 13:3474. [PMID: 38930006 PMCID: PMC11204497 DOI: 10.3390/jcm13123474] [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: 04/25/2024] [Revised: 06/06/2024] [Accepted: 06/10/2024] [Indexed: 06/28/2024] Open
Abstract
The incidence of obesity and asthma continues to enhance, significantly impacting global public health. Adipose tissue is an organ that secretes hormones and cytokines, causes meta-inflammation, and contributes to the intensification of bronchial hyperreactivity, oxidative stress, and consequently affects the different phenotypes of asthma in obese people. As body weight increases, the risk of severe asthma increases, as well as more frequent exacerbations requiring the use of glucocorticoids and hospitalization, which consequently leads to a deterioration of the quality of life. This review discusses the relationship between obesity and severe asthma, the underlying molecular mechanisms, changes in respiratory function tests in obese people, its impact on the occurrence of comorbidities, and consequently, a different response to conventional asthma treatment. The article also reviews research on possible future therapies for severe asthma. The manuscript is a narrative review of clinical trials in severe asthma and comorbid obesity. The articles were found in the PubMed database using the keywords asthma and obesity. Studies on severe asthma were then selected for inclusion in the article. The sections: 'The classification connected with asthma and obesity', 'Obesity-related changes in pulmonary functional tests', and 'Obesity and inflammation', include studies on subjects without asthma or non-severe asthma, which, according to the authors, familiarize the reader with the pathophysiology of obesity-related asthma.
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Affiliation(s)
- Aneta Elżbieta Olejnik
- Department of Pulmonology, Allergology and Pulmonary Oncology, Poznan University of Medical Sciences, Szamarzewskiego 84 Street, 60-569 Poznan, Poland;
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Russjan E. The Role of Peptides in Asthma-Obesity Phenotype. Int J Mol Sci 2024; 25:3213. [PMID: 38542187 PMCID: PMC10970696 DOI: 10.3390/ijms25063213] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 03/08/2024] [Accepted: 03/10/2024] [Indexed: 01/04/2025] Open
Abstract
The co-occurrence of asthma and obesity is becoming an increasingly common health problem. It became clear that both diseases are closely related, since overweight/obesity are associated with an increased risk of asthma development, and more than half of the subjects with severe or difficult-to-treat asthma are obese. Currently, there are no specific guidelines for the treatment of this group of patients. The mechanisms involved in the asthma-obesity phenotype include low-grade chronic inflammation and changes in pulmonary physiology. However, genetic predispositions, gender differences, comorbid conditions, and gut microbiota also seem to be important. Regulatory peptides affect many processes related to the functioning of the respiratory tract and adipose tissue. Adipokines such as leptin, adiponectin, resistin, and the less studied omentin, chemerin, and visfatin, as well as the gastrointestinal hormones ghrelin, cholecystokinin, glucagon-like peptide-1, and neuropeptides, including substance P or neuropeptide Y, can play a significant role in asthma with obesity. The aim of this article is to provide a concise review of the contribution of particular peptides in inflammatory reactions, obesity, asthma, and a combination of both diseases, as well as emphasize their potential role in the effective treatment of the asthma-obesity phenotype in the future.
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Affiliation(s)
- Ewelina Russjan
- Department of Respiration Physiology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Pawińskiego 5 St., 02-106 Warsaw, Poland
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Bradley D, Deng T, Shantaram D, Hsueh WA. Orchestration of the Adipose Tissue Immune Landscape by Adipocytes. Annu Rev Physiol 2024; 86:199-223. [PMID: 38345903 DOI: 10.1146/annurev-physiol-042222-024353] [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: 02/15/2024]
Abstract
Obesity is epidemic and of great concern because of its comorbid and costly inflammatory-driven complications. Extensive investigations in mice have elucidated highly coordinated, well-balanced interactions between adipocytes and immune cells in adipose tissue that maintain normal systemic metabolism in the lean state, while in obesity, proinflammatory changes occur in nearly all adipose tissue immune cells. Many of these changes are instigated by adipocytes. However, less is known about obesity-induced adipose-tissue immune cell alterations in humans. Upon high-fat diet feeding, the adipocyte changes its well-known function as a metabolic cell to assume the role of an immune cell, orchestrating proinflammatory changes that escalate inflammation and progress during obesity. This transformation is particularly prominent in humans. In this review, we (a) highlight a leading and early role for adipocytes in promulgating inflammation, (b) discuss immune cell changes and the time course of these changes (comparing humans and mice when possible), and (c) note how reversing proinflammatory changes in most types of immune cells, including adipocytes, rescues adipose tissue from inflammation and obese mice from insulin resistance.
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Affiliation(s)
- David Bradley
- Diabetes and Metabolism Research Center, Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA;
- Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Pennsylvania State Health Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA;
| | - Tuo Deng
- Second Xiangya Hospital, Central South University, Changsha, China
| | - Dharti Shantaram
- Diabetes and Metabolism Research Center, Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA;
| | - Willa A Hsueh
- Diabetes and Metabolism Research Center, Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA;
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Jeerawattanawart S, Hansakon A, Roytrakul S, Angkasekwinai P. Regulation and function of adiponectin in the intestinal epithelial cells in response to Trichinella spiralis infection. Sci Rep 2023; 13:14004. [PMID: 37635188 PMCID: PMC10460792 DOI: 10.1038/s41598-023-41377-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Accepted: 08/25/2023] [Indexed: 08/29/2023] Open
Abstract
Besides metabolic homeostasis regulation, adipokines are recently emerged as important players in regulating immunity and inflammation. Helminth infection has known to modulate circulating adipokine secretion; however, the regulation and function of adipokines in response to helminth infection is still unclear. Here, we investigated the regulation and function of adiponectin during T. spiralis infection. While there was no change in circulating level of adiponectin, we found an increased adiponectin, but not leptin expression in the small intestine. Interestingly, the intestinal adiponectin expression was strongly associated with the expression of epithelial cell-derived cytokines IL-25, IL-33, and TSLP following infection. Indeed, mice deficiency of IL-25 receptor exhibited no intestinal adiponectin induction upon helminth infection. Interestingly, IL-25-induced adiponectin modulated intestinal epithelial cell responses by enhancing occludin and CCL17 expression. Using LPS-induced intestinal epithelial barrier dysfunctions in a Caco-2 cell monolayer model, adiponectin pretreatment enhanced a Transepithelial electrical resistance (TEER) and occludin expression. More importantly, adiponectin pretreatment of Caco2 cells prevented T. spiralis larval invasion in vitro and its administration during infection enhanced intestinal IL-13 secretion and worm expulsion in vivo. Altogether, our data suggest that intestinal adiponectin expression induced by helminth infection through the regulation of IL-25 promotes worm clearance and intestinal barrier function.
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Affiliation(s)
- Siranart Jeerawattanawart
- Department of Medical Technology, Faculty of Allied Health Sciences, Thammasat University, Pathum Thani, 12120, Thailand
- Graduate Program in Biomedical Sciences, Faculty of Allied Health Sciences, Thammasat University, Pathum Thani, 12120, Thailand
| | - Adithap Hansakon
- Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, 12120, Thailand
| | - Sittiruk Roytrakul
- Functional Proteomics Technology Laboratory, Functional Ingredients and Food Innovation Research Group, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathum Thani, 12120, Thailand
| | - Pornpimon Angkasekwinai
- Department of Medical Technology, Faculty of Allied Health Sciences, Thammasat University, Pathum Thani, 12120, Thailand.
- Research Unit in Molecular Pathogenesis and Immunology of Infectious Diseases, Thammasat University, Pathum Thani, 12120, Thailand.
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Lempesis IG, Georgakopoulou VE. Implications of obesity and adiposopathy on respiratory infections; focus on emerging challenges. World J Clin Cases 2023; 11:2925-2933. [PMID: 37215426 PMCID: PMC10198078 DOI: 10.12998/wjcc.v11.i13.2925] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Revised: 02/17/2023] [Accepted: 03/30/2023] [Indexed: 04/25/2023] Open
Abstract
Obesity is characterized by excessive adipose tissue accumulation, which impacts physiological, metabolic, and immune functions. Several respiratory infections, including bacterial pneumonia, influenza, and coronavirus disease 2019, appear to be linked to unfavorable results in individuals with obesity. These may be attributed to the direct mechanical/physiological effects of excess body fat on the lungs’ function. Notably, adipose tissue dysfunction is associated with a low-grade chronic inflammatory status and hyperleptinemia, among other characteristics. These have all been linked to immune system dysfunction and weakened immune responses to these infections. A better understanding and clinical awareness of these risk factors are necessary for better disease outcomes.
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Affiliation(s)
- Ioannis G Lempesis
- Department of Infectious Diseases-COVID-19 Unit, Laiko General Hospital, Athens 11527, Greece
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Zhang KW, Jia Y, Li YY, Guo DY, Li XX, Hu K, Qian XX, Chen ZH, Wu JJ, Yuan ZD, Yuan FL. LEP and LEPR are possibly a double-edged sword for wound healing. J Cell Physiol 2023; 238:355-365. [PMID: 36571294 DOI: 10.1002/jcp.30936] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Revised: 12/05/2022] [Accepted: 12/13/2022] [Indexed: 12/27/2022]
Abstract
Wound healing is a complex and error-prone process. Wound healing in adults often leads to the formation of scars, a type of fibrotic tissue that lacks skin appendages. Hypertrophic scars and keloids can also form when the wound-healing process goes wrong. Leptin (Lep) and leptin receptors (LepRs) have recently been shown to affect multiple stages of wound healing. This effect, however, is paradoxical for scarless wound healing. On the one hand, Lep exerts pro-inflammatory and profibrotic effects; on the other hand, Lep can regulate hair follicle growth. This paper summarises the role of Lep and LepRs on cells in different stages of wound healing, briefly introduces the process of wound healing and Lep and LepRs, and examines the possibility of promoting scarless wound healing through spatiotemporal, systemic, and local regulation of Lep levels and the binding of Lep and LepRs.
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Affiliation(s)
- Kai-Wen Zhang
- Department of Medicine, Institute of Integrated Traditional Chinese and Western Medicine, Wuxi Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Traditional Chinese Medicine, Wuxi, China
| | - Yuan Jia
- Department of Medicine, Institute of Integrated Traditional Chinese and Western Medicine, Wuxi Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Traditional Chinese Medicine, Wuxi, China
| | - Yue-Yue Li
- Affiliated Hospital of Jiangnan University, Wuxi, China
| | - Dan-Yang Guo
- Affiliated Hospital of Jiangnan University, Wuxi, China
| | - Xiao-Xiao Li
- Department of Medicine, Institute of Integrated Traditional Chinese and Western Medicine, Wuxi Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Traditional Chinese Medicine, Wuxi, China
| | - Kai Hu
- Department of Medicine, Institute of Integrated Traditional Chinese and Western Medicine, Wuxi Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Traditional Chinese Medicine, Wuxi, China
| | - Xiao-Xi Qian
- Department of Medicine, Institute of Integrated Traditional Chinese and Western Medicine, Wuxi Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Traditional Chinese Medicine, Wuxi, China
| | - Zhong-Hua Chen
- Department of Medicine, The Nantong University, Nantong, China
| | - Jun-Jie Wu
- Institute of Integrated Chinese and Western Medicine, The Hospital Affiliated to Jiangnan University, Wuxi, China
| | - Zheng-Dong Yuan
- Institute of Integrated Chinese and Western Medicine, The Hospital Affiliated to Jiangnan University, Wuxi, China
| | - Feng-Lai Yuan
- Department of Medicine, Institute of Integrated Traditional Chinese and Western Medicine, Wuxi Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Traditional Chinese Medicine, Wuxi, China.,Affiliated Hospital of Jiangnan University, Wuxi, China.,Institute of Integrated Chinese and Western Medicine, The Hospital Affiliated to Jiangnan University, Wuxi, China
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9
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Costa KB, Garcia BCC, Costa MLB, Pena YG, Figueiredo EAB, Ottoni MHF, Santos JD, de Oliveira Ottone V, de Oliveira DB, Rocha-Vieira E. Association between Anti-DENV IgM Serum Prevalence and CD11b Expression by Classical Monocytes in Obesity. Viruses 2023; 15:234. [PMID: 36680274 PMCID: PMC9865527 DOI: 10.3390/v15010234] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Revised: 01/10/2023] [Accepted: 01/12/2023] [Indexed: 01/18/2023] Open
Abstract
Dengue and obesity are currently highly prevalent conditions worldwide and the association between these two conditions may result in greater risk for DENV infection and disease severity. In this study the association between obesity and recent, inapparent dengue was investigated. Serum DENV IgM and NS1 were evaluated in 49 adult volunteers (15 lean and 34 individuals with obesity, according to body mass index), between September 2017 and June 2018. Adiposity, endocrine, metabolic, and immune data of the participants were also obtained. None of the study participants tested positive for the DENV NS1 antigen. DENV IgM was detected in 33.3% of the lean individuals, and in 44.1% of those with obesity; the presence of DENV IgM was not associated with body mass index (OR = 1.32, 95% CI = 0.59-2.98, p = 0.48). However, body fat index was higher in obese individuals who had recent inapparent dengue (14.7 ± 3.1 versus 12.7 ± 2.1 kg/m2, p = 0.04), as was the expression of CD11b by classical (CD14++CD16-) monocytes (1103.0 ± 311.3 versus 720.3 ± 281.1 mean fluoresce intensity). Our findings suggest an association between adiposity and recent inapparent dengue and the involvement of classical monocytes in this association.
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Affiliation(s)
- Karine Beatriz Costa
- Programa Multicêntrico de Pós-Graduação em Ciências Fisiológicas, Universidade Federal dos Vales do Jequitinonha e Mucuri, Diamantina 39100-000, MG, Brazil
- Departamento de Medicina, Universidade Federal de Juiz de Fora, Governador Valadares 35010-180, MG, Brazil
- Laboratory of Exercise Biology and Immunometabolism, Centro Integrado de Pós-Graduação e Pesquisa em Saúde, Universidade Federal dos Vales do Jequitinonha e Mucuri, Diamantina 39100-000, MG, Brazil
| | - Bruna Caroline Chaves Garcia
- Programa Multicêntrico de Pós-Graduação em Ciências Fisiológicas, Universidade Federal dos Vales do Jequitinonha e Mucuri, Diamantina 39100-000, MG, Brazil
- Laboratory of Exercise Biology and Immunometabolism, Centro Integrado de Pós-Graduação e Pesquisa em Saúde, Universidade Federal dos Vales do Jequitinonha e Mucuri, Diamantina 39100-000, MG, Brazil
| | - Marina Luiza Baêta Costa
- Laboratory of Exercise Biology and Immunometabolism, Centro Integrado de Pós-Graduação e Pesquisa em Saúde, Universidade Federal dos Vales do Jequitinonha e Mucuri, Diamantina 39100-000, MG, Brazil
| | - Yara Gomes Pena
- Laboratory of Exercise Biology and Immunometabolism, Centro Integrado de Pós-Graduação e Pesquisa em Saúde, Universidade Federal dos Vales do Jequitinonha e Mucuri, Diamantina 39100-000, MG, Brazil
| | - Eduardo Augusto Barbosa Figueiredo
- Laboratory of Exercise Biology and Immunometabolism, Centro Integrado de Pós-Graduação e Pesquisa em Saúde, Universidade Federal dos Vales do Jequitinonha e Mucuri, Diamantina 39100-000, MG, Brazil
| | - Marcelo Henrique Fernandes Ottoni
- Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal dos Vales do Jequitinonha e Mucuri, Diamantina 39100-000, MG, Brazil
| | - Juliane Duarte Santos
- Programa Multicêntrico de Pós-Graduação em Ciências Fisiológicas, Universidade Federal dos Vales do Jequitinonha e Mucuri, Diamantina 39100-000, MG, Brazil
| | - Vinícius de Oliveira Ottone
- Laboratory of Exercise Biology and Immunometabolism, Centro Integrado de Pós-Graduação e Pesquisa em Saúde, Universidade Federal dos Vales do Jequitinonha e Mucuri, Diamantina 39100-000, MG, Brazil
| | - Danilo Bretas de Oliveira
- Programa Multicêntrico de Pós-Graduação em Ciências Fisiológicas, Universidade Federal dos Vales do Jequitinonha e Mucuri, Diamantina 39100-000, MG, Brazil
- Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal dos Vales do Jequitinonha e Mucuri, Diamantina 39100-000, MG, Brazil
| | - Etel Rocha-Vieira
- Programa Multicêntrico de Pós-Graduação em Ciências Fisiológicas, Universidade Federal dos Vales do Jequitinonha e Mucuri, Diamantina 39100-000, MG, Brazil
- Laboratory of Exercise Biology and Immunometabolism, Centro Integrado de Pós-Graduação e Pesquisa em Saúde, Universidade Federal dos Vales do Jequitinonha e Mucuri, Diamantina 39100-000, MG, Brazil
- Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal dos Vales do Jequitinonha e Mucuri, Diamantina 39100-000, MG, Brazil
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Watanabe K, Suzukawa M, Kawauchi-Watanabe S, Igarashi S, Asari I, Imoto S, Tashimo H, Fukami T, Hebisawa A, Tohma S, Nagase T, Ohta K. Leptin-producing monocytes in the airway submucosa may contribute to asthma pathogenesis. Respir Investig 2023; 61:5-15. [PMID: 36369154 DOI: 10.1016/j.resinv.2022.09.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Revised: 09/21/2022] [Accepted: 09/27/2022] [Indexed: 11/10/2022]
Abstract
BACKGROUND Obesity leads to an increase in the incidence and severity of asthma. Adipokines, such as leptin, secreted by adipocytes induce systemic inflammation, causing airway inflammation. We previously reported that leptin activates both inflammatory and structural cells, including lung fibroblasts. However, little is known about the differential leptin expression and responsiveness to leptin in asthmatic individuals and healthy controls (HC). In this study, we investigated the expression and origin of leptin in asthmatic airways. We also compared the effect of leptin on asthmatic and HC fibroblasts. METHODS Lung specimens from asthmatic and non-asthmatic patients were analyzed by immunohistochemical staining using anti-leptin and anti-CD163 antibodies. Leptin mRNA and protein levels in human monocytes were detected by real-time PCR and western blotting and ELISA, respectively. We used flow cytometry to analyze asthmatic and HC lung fibroblasts for leptin receptor (Ob-R) expression. Further, we determined cytokine levels using cytometric bead array and ELISA and intracellular phosphorylation of specific signaling molecules using western blotting. RESULTS Asthma specimens displayed accumulation of leptin-positive inflammatory cells, which were also positive for CD163, a high-affinity scavenger receptor expressed by monocytes and macrophages. Leptin expression was observed at both transcript and protein levels in human blood-derived monocytes. No significant differences were observed between asthmatic and HC lung fibroblasts in Ob-R expression, cytokine production, and intracellular phosphorylation of p38 mitogen-activated protein kinase. CONCLUSIONS Our findings reveal similar responsiveness of control and asthmatic fibroblasts to leptin. However, the accumulation of inflammatory leptin-producing monocytes in the airway may contribute to the pathogenesis of asthma.
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Affiliation(s)
- Kaoru Watanabe
- National Hospital Organization Tokyo National Hospital, 3-1-1 Takeoka, Kiyose-City, Tokyo 204-8585, Japan; Department of Respiratory Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Maho Suzukawa
- National Hospital Organization Tokyo National Hospital, 3-1-1 Takeoka, Kiyose-City, Tokyo 204-8585, Japan.
| | - Shizuka Kawauchi-Watanabe
- National Hospital Organization Tokyo National Hospital, 3-1-1 Takeoka, Kiyose-City, Tokyo 204-8585, Japan; Department of Respiratory Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Sayaka Igarashi
- National Hospital Organization Tokyo National Hospital, 3-1-1 Takeoka, Kiyose-City, Tokyo 204-8585, Japan
| | - Isao Asari
- National Hospital Organization Tokyo National Hospital, 3-1-1 Takeoka, Kiyose-City, Tokyo 204-8585, Japan
| | - Sahoko Imoto
- National Hospital Organization Tokyo National Hospital, 3-1-1 Takeoka, Kiyose-City, Tokyo 204-8585, Japan; Department of Respiratory Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Hiroyuki Tashimo
- National Hospital Organization Tokyo National Hospital, 3-1-1 Takeoka, Kiyose-City, Tokyo 204-8585, Japan
| | - Takeshi Fukami
- National Hospital Organization Tokyo National Hospital, 3-1-1 Takeoka, Kiyose-City, Tokyo 204-8585, Japan
| | - Akira Hebisawa
- National Hospital Organization Tokyo National Hospital, 3-1-1 Takeoka, Kiyose-City, Tokyo 204-8585, Japan; Department of Histopathology, Asahi General Hospital, I-1326, Asahi City, Chiba 289-2511, Japan
| | - Shigeto Tohma
- National Hospital Organization Tokyo National Hospital, 3-1-1 Takeoka, Kiyose-City, Tokyo 204-8585, Japan
| | - Takahide Nagase
- Department of Respiratory Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Ken Ohta
- National Hospital Organization Tokyo National Hospital, 3-1-1 Takeoka, Kiyose-City, Tokyo 204-8585, Japan; Japan Anti-Tuberculosis Association, Fukujuji Hospital, 3-1-24 Matsuyama, Kiyose-City, Tokyo 204-8522, Japan
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11
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Abend Bardagi A, Dos Santos Paschoal C, Favero GG, Riccetto L, Alexandrino Dias ML, Guerra Junior G, Degasperi G. Leptin's Immune Action: A Review Beyond Satiety. Immunol Invest 2023; 52:117-133. [PMID: 36278927 DOI: 10.1080/08820139.2022.2129381] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The adipose tissue is an endocrine organ that secretes adipokines such as leptin, which is one of the most important hormones for controlling satiety, metabolism, and energy homeostasis. This hormone acts in the regulation of innate and adaptive immune responses since immune cells have leptin receptors from which this hormone initiates its biological action. These receptors have been identified in hematopoietic stem cells in the bone marrow and mature immune cells, inducing signaling pathways mediated by JAK/STAT, PI3K, and ERK 1/2. It is known that the bone marrow also contains leptin-producing adipocytes, which are crucial for regulating hematopoiesis through largely unknown mechanisms. Therefore, we have reviewed the roles of leptin inside and outside the bone marrow, going beyond its action in the control of satiety.
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Affiliation(s)
- Alice Abend Bardagi
- Center for Health Sciences, School of Medical Sciences, Pontifícia Universidade Católica de Campinas (PUC-Campinas), Campinas, Brazil
| | - Clarissa Dos Santos Paschoal
- Center for Health Sciences, School of Medical Sciences, Pontifícia Universidade Católica de Campinas (PUC-Campinas), Campinas, Brazil
| | - Giovanna Ganem Favero
- Center for Health Sciences, School of Medical Sciences, Pontifícia Universidade Católica de Campinas (PUC-Campinas), Campinas, Brazil
| | - Luisa Riccetto
- Center for Health Sciences, School of Medical Sciences, Pontifícia Universidade Católica de Campinas (PUC-Campinas), Campinas, Brazil
| | - Maria Luisa Alexandrino Dias
- Center for Health Sciences, School of Medical Sciences, Pontifícia Universidade Católica de Campinas (PUC-Campinas), Campinas, Brazil
| | - Gil Guerra Junior
- Center for Investigation in Pediatrics (CIPED), School of Medical Sciences, Universidade Estadual de Campinas (Unicamp), Campinas, Brazil
| | - Giovanna Degasperi
- Center for Health Sciences, School of Medical Sciences, Pontifícia Universidade Católica de Campinas (PUC-Campinas), Campinas, Brazil
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12
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13
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Wang Y, Hu C. Leptin and Asthma: What Are the Interactive Correlations? Biomolecules 2022; 12:biom12121780. [PMID: 36551211 PMCID: PMC9775505 DOI: 10.3390/biom12121780] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Revised: 11/25/2022] [Accepted: 11/28/2022] [Indexed: 12/02/2022] Open
Abstract
Leptin is an adipokine directly correlated with the proinflammatory obese-associated phenotype. Leptin has been demonstrated to inhibit adipogenesis, promote fat demarcation, promote a chronic inflammatory state, increase insulin sensitivity, and promote angiogenesis. Leptin, a regulator of the immune response, is implicated in the pathology of asthma. Studies involved in the key cell reaction and animal models of asthma have provided vital insights into the proinflammatory role of leptin in asthma. Many studies described the immune cell and related cellular pathways activated by leptin, which are beneficial in asthma development and increasing exacerbations. Subsequent studies relating to animal models support the role of leptin in increasing inflammatory cell infiltration, airway hyperresponsiveness, and inflammatory responses. However, the conclusive effects of leptin in asthma are not well elaborated. In the present study, we explored the general functions and the clinical cohort study supporting the association between leptin and asthma. The main objective of our review is to address the knowns and unknowns of leptin on asthma. In this perspective, the arguments about the different faces of leptin in asthma are provided to picture the potential directions, thus yielding a better understanding of asthma development.
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Affiliation(s)
- Yang Wang
- Department of Respiratory Medicine (Department of Respiratory and Critical Care Medicine), Xiangya Hospital, Central South University, Changsha 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Chengping Hu
- Department of Respiratory Medicine (Department of Respiratory and Critical Care Medicine), Xiangya Hospital, Central South University, Changsha 410008, China
- Correspondence:
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14
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Mintoff D, Benhadou F, Pace NP, Frew JW. Metabolic syndrome and hidradenitis suppurativa: epidemiological, molecular, and therapeutic aspects. Int J Dermatol 2021; 61:1175-1186. [PMID: 34530487 DOI: 10.1111/ijd.15910] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Accepted: 08/28/2021] [Indexed: 12/12/2022]
Abstract
Hidradenitis suppurativa (HS) is a chronic, suppurative condition of the pilosebaceous unit. Patients suffering from HS demonstrate a molecular profile in keeping with a state of systemic inflammation and are often found to fit the criteria for a diagnosis of metabolic syndrome (MetS). In this paper, we review the literature with regards to established data on the prevalence of MetS in HS patients and revise the odds ratio of comorbid disease. Furthermore, we attempt to draw parallels between inflammatory pathways in HS and MetS and evaluate how convergences may explain the risk of comorbid disease, necessitating the need for multidisciplinary care.
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Affiliation(s)
- Dillon Mintoff
- Department of Dermatology, Mater Dei Hospital, Msida, Malta.,European Hidradenitis Suppurativa Foundation e.V, Dessau, Germany.,Department of Pathology, Faculty of Medicine and Surgery, University of Malta, Msida, Malta
| | - Farida Benhadou
- European Hidradenitis Suppurativa Foundation e.V, Dessau, Germany.,Department of Dermatology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium
| | - Nikolai P Pace
- Department of Pathology, Faculty of Medicine and Surgery, University of Malta, Msida, Malta.,Centre for Molecular Medicine and Biobanking, Faculty of Medicine and Surgery, University of Malta, Msida, Malta
| | - John W Frew
- Department of Dermatology, Liverpool Hospital, University of New South Wales, Sydney, NSW, Australia
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15
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Blaszczak AM, Jalilvand A, Hsueh WA. Adipocytes, Innate Immunity and Obesity: A Mini-Review. Front Immunol 2021; 12:650768. [PMID: 34248937 PMCID: PMC8264354 DOI: 10.3389/fimmu.2021.650768] [Citation(s) in RCA: 64] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Accepted: 04/28/2021] [Indexed: 12/12/2022] Open
Abstract
The role of adipose tissue (AT) inflammation in obesity and its multiple related-complications is a rapidly expanding area of scientific interest. Within the last 30 years, the role of the adipocyte as an endocrine and immunologic cell has been progressively established. Like the macrophage, the adipocyte is capable of linking the innate and adaptive immune system through the secretion of adipokines and cytokines; exosome release of lipids, hormones, and microRNAs; and contact interaction with other immune cells. Key innate immune cells in AT include adipocytes, macrophages, neutrophils, and innate lymphoid cells type 2 (ILC2s). The role of the innate immune system in promoting adipose tissue inflammation in obesity will be highlighted in this review. T cells and B cells also play important roles in contributing to AT inflammation and are discussed in this series in the chapter on adaptive immunity.
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Affiliation(s)
- Alecia M Blaszczak
- Hsueh Laboratory, The Ohio State University Wexner Medical Center, Diabetes and Metabolism Research Center, Columbus, OH, United States
| | - Anahita Jalilvand
- Hsueh Laboratory, The Ohio State University Wexner Medical Center, Diabetes and Metabolism Research Center, Columbus, OH, United States
| | - Willa A Hsueh
- Hsueh Laboratory, The Ohio State University Wexner Medical Center, Diabetes and Metabolism Research Center, Columbus, OH, United States
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16
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Cordero-Barreal A, González-Rodríguez M, Ruiz-Fernández C, Eldjoudi DA, AbdElHafez YRF, Lago F, Conde J, Gómez R, González-Gay MA, Mobasheri A, Pino J, Gualillo O. An Update on the Role of Leptin in the Immuno-Metabolism of Cartilage. Int J Mol Sci 2021; 22:ijms22052411. [PMID: 33673730 PMCID: PMC7957536 DOI: 10.3390/ijms22052411] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 02/20/2021] [Accepted: 02/25/2021] [Indexed: 12/14/2022] Open
Abstract
Since its discovery in 1994, leptin has been considered as an adipokine with pleiotropic effects. In this review, we summarize the actual information about the impact of this hormone on cartilage metabolism and pathology. Leptin signalling depends on the interaction with leptin receptor LEPR, being the long isoform of the receptor (LEPRb) the one with more efficient intracellular signalling. Chondrocytes express the long isoform of the leptin receptor and in these cells, leptin signalling, alone or in combination with other molecules, induces the expression of pro-inflammatory molecules and cartilage degenerative enzymes. Leptin has been shown to increase the proliferation and activation of immune cells, increasing the severity of immune degenerative cartilage diseases. Leptin expression in serum and synovial fluid are related to degenerative diseases such as osteoarthritis (OA), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Inhibition of leptin signalling showed to have protective effects in these diseases showing the key role of leptin in cartilage degeneration.
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Affiliation(s)
- Alfonso Cordero-Barreal
- SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), The NEIRID Group (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Santiago University Clinical Hospital, Building C, Travesía da Choupana S/N, 15706 Santiago de Compostela, Spain; (A.C.-B.); (M.G.-R.); (C.R.-F.); (D.A.E.); (Y.R.F.A.)
| | - María González-Rodríguez
- SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), The NEIRID Group (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Santiago University Clinical Hospital, Building C, Travesía da Choupana S/N, 15706 Santiago de Compostela, Spain; (A.C.-B.); (M.G.-R.); (C.R.-F.); (D.A.E.); (Y.R.F.A.)
| | - Clara Ruiz-Fernández
- SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), The NEIRID Group (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Santiago University Clinical Hospital, Building C, Travesía da Choupana S/N, 15706 Santiago de Compostela, Spain; (A.C.-B.); (M.G.-R.); (C.R.-F.); (D.A.E.); (Y.R.F.A.)
| | - Djedjiga Ait Eldjoudi
- SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), The NEIRID Group (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Santiago University Clinical Hospital, Building C, Travesía da Choupana S/N, 15706 Santiago de Compostela, Spain; (A.C.-B.); (M.G.-R.); (C.R.-F.); (D.A.E.); (Y.R.F.A.)
| | - Yousof Ramadan Farrag AbdElHafez
- SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), The NEIRID Group (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Santiago University Clinical Hospital, Building C, Travesía da Choupana S/N, 15706 Santiago de Compostela, Spain; (A.C.-B.); (M.G.-R.); (C.R.-F.); (D.A.E.); (Y.R.F.A.)
| | - Francisca Lago
- Molecular and Cellular Cardiology Group, SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), Research Laboratory 7, Santiago University Clinical Hospital, 15706 Santiago de Compostela, Spain; (F.L.); (J.C.)
| | - Javier Conde
- Molecular and Cellular Cardiology Group, SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), Research Laboratory 7, Santiago University Clinical Hospital, 15706 Santiago de Compostela, Spain; (F.L.); (J.C.)
| | - Rodolfo Gómez
- SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), The Muscle-Skeletal Pathology Group, Santiago University Clinical Hospital, Building C, Travesía da Choupana S/N, 15706 Santiago de Compostela, Spain;
| | - Miguel Angel González-Gay
- Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Universidad de Cantabria and IDIVAL, Hospital Universitario Marqués de Valdecilla, Av. Valdecilla, 39008 Santander, Spain;
| | - Ali Mobasheri
- Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, FIN-90230 Oulu, Finland;
- Department of Regenerative Medicine, State Research Institute, Centre for Innovative Medicine, LT-08406 Vilnius, Lithuania
- Departments of Orthopedics, Rheumatology and Clinical Immunology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands
- Department of Joint Surgery, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
| | - Jesus Pino
- SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), The NEIRID Group (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Santiago University Clinical Hospital, Building C, Travesía da Choupana S/N, 15706 Santiago de Compostela, Spain; (A.C.-B.); (M.G.-R.); (C.R.-F.); (D.A.E.); (Y.R.F.A.)
- Correspondence: (J.P.); (O.G.); Tel./Fax: +34-981950905 (O.G.)
| | - Oreste Gualillo
- SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), The NEIRID Group (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Santiago University Clinical Hospital, Building C, Travesía da Choupana S/N, 15706 Santiago de Compostela, Spain; (A.C.-B.); (M.G.-R.); (C.R.-F.); (D.A.E.); (Y.R.F.A.)
- Correspondence: (J.P.); (O.G.); Tel./Fax: +34-981950905 (O.G.)
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Żelechowska P, Brzezińska-Błaszczyk E, Kusowska A, Kozłowska E. The role of adipokines in the modulation of lymphoid lineage cell development and activity: An overview. Obes Rev 2020; 21:e13055. [PMID: 32638520 DOI: 10.1111/obr.13055] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Revised: 04/27/2020] [Accepted: 05/12/2020] [Indexed: 12/15/2022]
Abstract
Adipokines are predominantly known to play a vital role in the control of food intake, energy homeostasis and regulation of glucose and lipid metabolism. However, evidence supporting the concept of their extensive involvement in immune system defence mechanisms and inflammatory processes continues to grow. Some of the adipokines, that is, leptin and resistin, have been recognized to exhibit mainly pro-inflammatory properties, whereas others such as visfatin, chemerin, apelin and vaspin have been found to exert regulatory effects. In contrast, adiponectin or omentin are known for their anti-inflammatory activities. Hence, adipokines influence the activity of various cells engaged in innate immune response and inflammatory processes mainly by affecting adhesion molecule expression, chemotaxis, apoptosis and phagocytosis, as well as mediators production and release. However, much less is known about the role of adipokines in processes involving lymphoid lineage cells. This review summarizes the current knowledge regarding the importance of different adipokines in the lymphopoiesis, recirculation, differentiation and polarization of lymphoid lineage cells. It also provides insight into the influence of selected adipokines on the activity of those cells in tissues.
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Affiliation(s)
- Paulina Żelechowska
- Faculty of Health Sciences, Department of Experimental Immunology, Medical University of Lodz, Lodz, Poland
| | - Ewa Brzezińska-Błaszczyk
- Faculty of Health Sciences, Department of Experimental Immunology, Medical University of Lodz, Lodz, Poland
| | | | - Elżbieta Kozłowska
- Faculty of Health Sciences, Department of Experimental Immunology, Medical University of Lodz, Lodz, Poland
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18
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Wang F, Zuo Z, Yang Z, Chen K, Fang J, Cui H, Shu G, Zhou Y, Geng Y, Ouyang P. Delayed Pulmonary Apoptosis of Diet-Induced Obesity Mice following Escherichia coli Infection through the Mitochondrial Apoptotic Pathway. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2019; 2019:1968539. [PMID: 31772700 PMCID: PMC6854188 DOI: 10.1155/2019/1968539] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/25/2019] [Revised: 06/26/2019] [Accepted: 08/23/2019] [Indexed: 01/12/2023]
Abstract
Escherichia coli (E. coli) is one of pathogens causing nosocomial pneumonia and could induce pulmonary excessive apoptosis. Although much has been learned about metabolic diseases induced by obesity, the information linking bacterial pneumonia to obesity is limited. Accordingly, we investigated the apoptosis of normal (lean) and diet-induced obesity (DIO, fed a high-fat diet) mice after nasal instillation with E. coli. Lung tissues were obtained at 0 (preinfection), 12, 24, and 72 h after infection, and acute pulmonary inflammation was observed at 12 h. Elevated cell apoptosis and percentage of pulmonary cells depolarized with collapse of the mitochondrial transmembrane potential (Δψm) occurred in response to bacterial infection. The relative mRNA and protein expressions of Bax, caspase-3, and caspase-9 increased, but Bcl-2 decreased in the lung. Interestingly, the apoptotic percentage and most of apoptosis-associated factors mentioned above peaked at 12 or 24 h in the lean-E. coli group, while at 24 or 72 h in the DIO-E. coli group. Taken together, these findings indicated that the E. coli pneumonia caused excessive pulmonary apoptosis through the mitochondria-mediated pathway, and the apoptosis was delayed in the DIO mice with E. coli pneumonia.
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Affiliation(s)
- Fengyuan Wang
- College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, China
| | - Zhicai Zuo
- College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, China
| | - Zhuangzhi Yang
- Chengdu Academy of Agriculture and Forestry Sciences, Chengdu, Sichuan 611130, China
| | - Kejie Chen
- School of Public Health, Chengdu Medical College, Chengdu, Sichuan 610500, China
| | - Jing Fang
- College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, China
| | - Hengmin Cui
- College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, China
| | - Gang Shu
- College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, China
| | - Yi Zhou
- College of Life Science, Sichuan Agricultural University, Ya'an, Sichuan 625014, China
| | - Yi Geng
- College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, China
| | - Ping Ouyang
- College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, China
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19
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Al-Shibli SM, Harun N, Ashour AE, Mohd Kasmuri MHB, Mizan S. Expression of leptin and leptin receptors in colorectal cancer-an immunohistochemical study. PeerJ 2019; 7:e7624. [PMID: 31592340 PMCID: PMC6778430 DOI: 10.7717/peerj.7624] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2019] [Accepted: 08/06/2019] [Indexed: 01/22/2023] Open
Abstract
Obesity is demonstrated to be a risk factor in the development of cancers of various organs, such as colon, prostate, pancreas and so on. Leptine (LEP) is the most renowned of the adipokines. As a hormone, it mediates its effect through leptin receptor (LEPR), which is widely expressed in various tissues including colon mucosa. In this study, we have investigated the degree of expression of LEP and LEPR in colorectal cancer (CRC). We collected 44 surgically resected colon cancer tissues along with normal adjacent colon tissue (NACT) from a sample of CRC patients from the Malaysian population and looked for leptin and leptin receptors using immunohistochemistry (IHC). All the samples showed low presence of both LEP and LEPR in NACT, while both LEP and LEPR were present at high intensity in the cancerous tissues with 100% and 97.7% prevalence, respectively. Both were sparsed in the cytoplasm and were concentrated beneath the cell membrane. However, we did not find any significant correlation between their expression and pathological parameters like grade, tumor size, and lymph node involvement. Our study further emphasizes the possible causal role of LEP and LEPR with CRC, and also the prospect of using LEPR as a possible therapeutic target.
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Affiliation(s)
- Saad M Al-Shibli
- Department of Basic Medical Sciences, International Islamic University, Kuantan, Pahang, Malaysia
| | - Norra Harun
- Pathology Department, Hospital Tengku Ampuan Afzan, Kuantan, Pahang, Malaysia
| | - Abdelkader E Ashour
- Department of Basic Medical Sciences, International Islamic University, Kuantan, Pahang, Malaysia
| | - Mohd Hanif B Mohd Kasmuri
- Department of Pathology & Laboratory Medicine, International Islamic University, Kuantan, Pahang, Malaysia
| | - Shaikh Mizan
- Department of Basic Medical Sciences, International Islamic University, Kuantan, Pahang, Malaysia
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20
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Alti D, Sambamurthy C, Kalangi SK. Emergence of Leptin in Infection and Immunity: Scope and Challenges in Vaccines Formulation. Front Cell Infect Microbiol 2018; 8:147. [PMID: 29868503 PMCID: PMC5954041 DOI: 10.3389/fcimb.2018.00147] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2017] [Accepted: 04/20/2018] [Indexed: 01/01/2023] Open
Abstract
Deficiency of leptin (ob/ob) and/or desensitization of leptin signaling (db/db) and elevated expression of suppressor of cytokine signaling-3 (SOCS3) reported in obesity are also reported in a variety of pathologies including hypertriglyceridemia, insulin resistance, and malnutrition as the risk factors in host defense system. Viral infections cause the elevated SOCS3 expression, which inhibits leptin signaling. It results in immunosuppression by T-regulatory cells (Tregs). The host immunity becomes incompetent to manage pathogens' attack and invasion, which results in the accelerated infections and diminished vaccine-specific antibody response. Leptin was successfully used as mucosal vaccine adjuvant against Rhodococcus equi. Leptin induced the antibody response to Helicobacter pylori vaccination in mice. An integral leptin signaling in mucosal gut epithelial cells offered resistance against Clostridium difficile and Entameoba histolytica infections. We present in this review, the intervention of leptin in lethal diseases caused by microbial infections and propose the possible scope and challenges of leptin as an adjuvant tool in the development of effective vaccines.
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Affiliation(s)
- Dayakar Alti
- School of Life Sciences, University of Hyderabad, Hyderabad, India
| | | | - Suresh K Kalangi
- School of Life Sciences, University of Hyderabad, Hyderabad, India
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21
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Karlsson EA, Schultz-Cherry S, Rosch JW. Protective Capacity of Statins during Pneumonia Is Dependent on Etiological Agent and Obesity. Front Cell Infect Microbiol 2018; 8:41. [PMID: 29497602 PMCID: PMC5819214 DOI: 10.3389/fcimb.2018.00041] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2017] [Accepted: 01/31/2018] [Indexed: 01/14/2023] Open
Abstract
Acute respiratory infections are a leading cause of death worldwide. Clinical data is conflicted regarding whether statins improve outcomes for pneumonia. Potential confounding factors including specific etiology of pneumonia as well as obesity could potentially mask protective benefit. Obesity is a risk factor for high cholesterol, the main target for statin therapy. We demonstrate that statin intervention conferred no protective benefit in the context of wild-type mice regardless of infectious agent. Statin intervention conferred either a protective benefit, during influenza infection, or detrimental effect, in the case of pneumococcal infection, in obese animals. These data suggest etiology of pneumonia in the context of obesity could be dramatically altered by the protective effects of statin therapy during bacterial and viral pneumonia.
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Affiliation(s)
- Erik A Karlsson
- Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN, United States
| | - Stacey Schultz-Cherry
- Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN, United States
| | - Jason W Rosch
- Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN, United States
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22
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Souza-Almeida G, D'Avila H, Almeida PE, Luna-Gomes T, Liechocki S, Walzog B, Hepper I, Castro-Faria-Neto HC, Bozza PT, Bandeira-Melo C, Maya-Monteiro CM. Leptin Mediates In Vivo Neutrophil Migration: Involvement of Tumor Necrosis Factor-Alpha and CXCL1. Front Immunol 2018; 9:111. [PMID: 29467755 PMCID: PMC5808117 DOI: 10.3389/fimmu.2018.00111] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2017] [Accepted: 01/15/2018] [Indexed: 11/13/2022] Open
Abstract
Leptin directly activates macrophages and lymphocytes, but the role of leptin in neutrophil activation and migration is still controversial. Here, we investigate the in vivo mechanisms of neutrophil migration induced by leptin. The intraperitoneal injection of leptin (1 mg/kg) induces a time- and concentration-dependent neutrophil influx. We did not observe the enhancement of lipid bodies/droplets in neutrophils, after leptin treatment, as we had observed previously in peritoneal macrophages. The participation of leukotriene B4 (LTB4) in neutrophil recruitment triggered by leptin was investigated using different strategies. Leptin-induced neutrophil recruitment occurs both in the absence of 5-lipoxygenase activity in 5-lipoxygenase (5-LO)-/- mice and after the administration of either 5-LO inhibitor (Zileuton) or the LTB4 receptor antagonist (U-75302). Moreover, no direct induction of LTB4 by leptin could be observed. Neutrophil influx could not be prevented by the mammalian target of rapamycin (mTOR) inhibitor, rapamycin, contrasting with the leptin-induced signaling for lipid body formation in macrophage that is mTOR-dependent. Leptin administration led to tumor necrosis factor-alpha (TNFα) production by the peritoneal cells both in vivo and in vitro. In addition, neutrophil recruitment was inhibited in tumor necrosis factor receptor 1 (TNFR1-/-) mice, indicating a role for TNF in leptin-induced neutrophil recruitment to the peritoneal cavity. Leptin-induced neutrophil influx was PI3Kγ-dependent, as it was absent in PI3Kγ-/- mice. Accordingly, leptin induced the peritoneal cells to produce CXCL1, both in vivo and in vitro, and the neutrophil influx was ablated after using an antibody against CXCL1. Our results establish TNFα/TNFR1- and CXCL1-dependent signaling as important pathways for leptin-induced neutrophil migration in vivo.
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Affiliation(s)
- Glaucia Souza-Almeida
- Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
| | - Heloisa D'Avila
- Instituto de Ciências Biológicas, Universidade Federal de Juiz de Fora, Juiz de Fora, Brazil
| | - Patricia E Almeida
- Instituto de Ciências Biológicas, Universidade Federal de Juiz de Fora, Juiz de Fora, Brazil
| | - Tatiana Luna-Gomes
- Instituto de Ciências Biológicas, Universidade Federal de Juiz de Fora, Juiz de Fora, Brazil.,Departamento de Ciências da Natureza, Instituto de Aplicação Fernando Rodrigues da Silveira, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Sally Liechocki
- Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
| | - Barbara Walzog
- Walter Brendel Centre of Experimental Medicine, Department of Cardiovascular Physiology and Pathophysiology, Biomedical Center, Ludwig-Maximilians-Universität München, Munich, Germany
| | - Ingrid Hepper
- Walter Brendel Centre of Experimental Medicine, Department of Cardiovascular Physiology and Pathophysiology, Biomedical Center, Ludwig-Maximilians-Universität München, Munich, Germany
| | | | - Patricia T Bozza
- Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
| | - Christianne Bandeira-Melo
- Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Clarissa M Maya-Monteiro
- Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
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Faggioni R, Feingold KR, Grunfeld C. Leptin regulation of the immune response and the immunodeficiency of malnutrition. FASEB J 2001; 15:2565-71. [PMID: 11726531 DOI: 10.1096/fj.01-0431rev] [Citation(s) in RCA: 320] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Leptin is a 16 kDa protein mainly produced by adipose tissue in proportion to adipose tissue mass. Originally thought to be a satiety factor, leptin is a pleiotropic molecule. In addition to playing a role in energy regulation, leptin also regulates endocrine and immune functions. Both the structure of leptin and that of its receptor suggest that leptin might be classified as a cytokine. The secondary structure of leptin has similarities to the long-chain helical cytokines family, which includes interleukin 6 (IL-6), IL-11, CNTF, and LIF, and the leptin receptor is homologous to the gp-130 signal-transducing subunit of the IL-6-type cytokine receptors. Leptin plays a role in innate and acquired immunity. Leptin levels increase acutely during infection and inflammation, and may represent a protective component of the host response to inflammation. More important, leptin deficiency increases susceptibility to infectious and inflammatory stimuli and is associated with dysregulation of cytokine production. Leptin deficiency also causes a defect in hematopoiesis. Leptin regulates T cells responses, polarizing Th cells toward a Th1 phenotype. Low leptin levels occurring during starvation mediate the neuroendocrine and immune dysfunction of starvation.
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Affiliation(s)
- R Faggioni
- Department of Veterans Affairs Medical Center, University of California, San Francisco, San Francisco, California, 94121, USA.
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