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Villanueva-Carmona T, Cedó L, Madeira A, Ceperuelo-Mallafré V, Rodríguez-Peña MM, Núñez-Roa C, Maymó-Masip E, Repollés-de-Dalmau M, Badia J, Keiran N, Mirasierra M, Pimenta-Lopes C, Sabadell-Basallote J, Bosch R, Caubet L, Escolà-Gil JC, Fernández-Real JM, Vilarrasa N, Ventura F, Vallejo M, Vendrell J, Fernández-Veledo S. SUCNR1 signaling in adipocytes controls energy metabolism by modulating circadian clock and leptin expression. Cell Metab 2023; 35:601-619.e10. [PMID: 36977414 DOI: 10.1016/j.cmet.2023.03.004] [Citation(s) in RCA: 38] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Revised: 11/21/2022] [Accepted: 03/03/2023] [Indexed: 03/30/2023]
Abstract
Adipose tissue modulates energy homeostasis by secreting leptin, but little is known about the factors governing leptin production. We show that succinate, long perceived as a mediator of immune response and lipolysis, controls leptin expression via its receptor SUCNR1. Adipocyte-specific deletion of Sucnr1 influences metabolic health according to nutritional status. Adipocyte Sucnr1 deficiency impairs leptin response to feeding, whereas oral succinate mimics nutrient-related leptin dynamics via SUCNR1. SUCNR1 activation controls leptin expression via the circadian clock in an AMPK/JNK-C/EBPα-dependent manner. Although the anti-lipolytic role of SUCNR1 prevails in obesity, its function as a regulator of leptin signaling contributes to the metabolically favorable phenotype in adipocyte-specific Sucnr1 knockout mice under standard dietary conditions. Obesity-associated hyperleptinemia in humans is linked to SUCNR1 overexpression in adipocytes, which emerges as the major predictor of adipose tissue leptin expression. Our study establishes the succinate/SUCNR1 axis as a metabolite-sensing pathway mediating nutrient-related leptin dynamics to control whole-body homeostasis.
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Affiliation(s)
- Teresa Villanueva-Carmona
- Department of Endocrinology and Nutrition, Research Unit, Institut d'Investigació Sanitària Pere Virgili (IISPV), Hospital Universitari de Tarragona Joan XXIII, Tarragona 43005, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid 28029, Spain
| | - Lídia Cedó
- Department of Endocrinology and Nutrition, Research Unit, Institut d'Investigació Sanitària Pere Virgili (IISPV), Hospital Universitari de Tarragona Joan XXIII, Tarragona 43005, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid 28029, Spain
| | - Ana Madeira
- Department of Endocrinology and Nutrition, Research Unit, Institut d'Investigació Sanitària Pere Virgili (IISPV), Hospital Universitari de Tarragona Joan XXIII, Tarragona 43005, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid 28029, Spain
| | - Victòria Ceperuelo-Mallafré
- Department of Endocrinology and Nutrition, Research Unit, Institut d'Investigació Sanitària Pere Virgili (IISPV), Hospital Universitari de Tarragona Joan XXIII, Tarragona 43005, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid 28029, Spain; Department of Medicine and Surgery, Universitat Rovira i Virgili (URV), Reus 43201, Spain
| | - M-Mar Rodríguez-Peña
- Department of Endocrinology and Nutrition, Research Unit, Institut d'Investigació Sanitària Pere Virgili (IISPV), Hospital Universitari de Tarragona Joan XXIII, Tarragona 43005, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid 28029, Spain
| | - Catalina Núñez-Roa
- Department of Endocrinology and Nutrition, Research Unit, Institut d'Investigació Sanitària Pere Virgili (IISPV), Hospital Universitari de Tarragona Joan XXIII, Tarragona 43005, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid 28029, Spain
| | - Elsa Maymó-Masip
- Department of Endocrinology and Nutrition, Research Unit, Institut d'Investigació Sanitària Pere Virgili (IISPV), Hospital Universitari de Tarragona Joan XXIII, Tarragona 43005, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid 28029, Spain
| | - Maria Repollés-de-Dalmau
- Department of Endocrinology and Nutrition, Research Unit, Institut d'Investigació Sanitària Pere Virgili (IISPV), Hospital Universitari de Tarragona Joan XXIII, Tarragona 43005, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid 28029, Spain; Department of Medicine and Surgery, Universitat Rovira i Virgili (URV), Reus 43201, Spain
| | - Joan Badia
- Institut d'Oncologia de la Catalunya Sud, Hospital Universitari Sant Joan de Reus, IISPV, Reus 43204, Spain
| | - Noelia Keiran
- Department of Endocrinology and Nutrition, Research Unit, Institut d'Investigació Sanitària Pere Virgili (IISPV), Hospital Universitari de Tarragona Joan XXIII, Tarragona 43005, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid 28029, Spain
| | - Mercedes Mirasierra
- CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid 28029, Spain; Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas/Universidad Autónoma de Madrid (CSIC/UAM), Madrid 28029, Spain
| | - Carolina Pimenta-Lopes
- Departament de Ciències Fisiològiques, Universitat de Barcelona, IDIBELL, Hospitalet de Llobregat, Barcelona 08907, Spain
| | - Joan Sabadell-Basallote
- Department of Endocrinology and Nutrition, Research Unit, Institut d'Investigació Sanitària Pere Virgili (IISPV), Hospital Universitari de Tarragona Joan XXIII, Tarragona 43005, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid 28029, Spain
| | - Ramón Bosch
- Department of Pathology, Oncological Pathology and Bioinformatics Research Group, Hospital de Tortosa Verge de la Cinta, IISPV, Tortosa 43500, Spain
| | - Laura Caubet
- General and Digestive Surgery Service, Hospital Sant Pau i Santa Tecla, Institut d'Investigació Sanitària Pere Virgili, Tarragona 43003, Spain
| | - Joan Carles Escolà-Gil
- CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid 28029, Spain; Institut d'Investigacions Biomèdiques (IIB) Sant Pau, Barcelona 08041, Spain; Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Barcelona 08193, Spain
| | - José-Manuel Fernández-Real
- Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomèdica de Girona (IdIBGi), Salt 17190, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CB06/03/010), Instituto de Salud Carlos III, Madrid 28029, Spain; Department of Medical Sciences, School of Medicine, University of Girona, Girona 17004, Spain
| | - Nuria Vilarrasa
- CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid 28029, Spain; Department of Endocrinology and Nutrition, Hospital Universitari Bellvitge - IDIBELL, Hospitalet de Llobregat, Barcelona 08907, Spain
| | - Francesc Ventura
- Departament de Ciències Fisiològiques, Universitat de Barcelona, IDIBELL, Hospitalet de Llobregat, Barcelona 08907, Spain
| | - Mario Vallejo
- CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid 28029, Spain; Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas/Universidad Autónoma de Madrid (CSIC/UAM), Madrid 28029, Spain
| | - Joan Vendrell
- Department of Endocrinology and Nutrition, Research Unit, Institut d'Investigació Sanitària Pere Virgili (IISPV), Hospital Universitari de Tarragona Joan XXIII, Tarragona 43005, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid 28029, Spain; Department of Medicine and Surgery, Universitat Rovira i Virgili (URV), Reus 43201, Spain
| | - Sonia Fernández-Veledo
- Department of Endocrinology and Nutrition, Research Unit, Institut d'Investigació Sanitària Pere Virgili (IISPV), Hospital Universitari de Tarragona Joan XXIII, Tarragona 43005, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid 28029, Spain.
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Evans MC, Campbell RE, Anderson GM. Physiological regulation of leptin as an integrative signal of reproductive readiness. Curr Opin Pharmacol 2022; 67:102321. [PMID: 36427399 DOI: 10.1016/j.coph.2022.102321] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2022] [Accepted: 10/24/2022] [Indexed: 11/23/2022]
Abstract
Reproductive function is tightly regulated by both environmental and physiological factors. The adipose-derived hormone leptin has been identified as one such critical factor that relays information about peripheral energy availability to the centrally-governed HPG axis to ensure there is sufficient energy availability to support the high energy demands of mammalian reproduction. In the absence of adequate central leptin signaling, reproductive function is suppressed. While leptin levels are predominantly regulated by adiposity, circulating leptin levels are also under the modulatory influence of other factors, such as stress system activation, circadian rhythmicity, and immune activation and the inflammatory response. Furthermore, changes in leptin sensitivity can affect the degree to which leptin exerts its influence on the neuroendocrine reproductive axis. This review will discuss the different mechanisms by which leptin serves to integrate and relay information about metabolic, psychological, environmental and immune conditions to the central neuronal network that governs reproductive function.
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Affiliation(s)
- Maggie C Evans
- Centre for Neuroendocrinology, University of Otago School of Biomedical Sciences, Dunedin, New Zealand
| | - Rebecca E Campbell
- Centre for Neuroendocrinology, University of Otago School of Biomedical Sciences, Dunedin, New Zealand
| | - Greg M Anderson
- Centre for Neuroendocrinology, University of Otago School of Biomedical Sciences, Dunedin, New Zealand.
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Mankiewicz JL, Deck CA, Taylor JD, Douros JD, Borski RJ. Epinephrine and glucose regulation of leptin synthesis and secretion in a teleost fish, the tilapia (Oreochromis mossambicus). Gen Comp Endocrinol 2021; 302:113669. [PMID: 33242479 DOI: 10.1016/j.ygcen.2020.113669] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Revised: 11/06/2020] [Accepted: 11/16/2020] [Indexed: 12/24/2022]
Abstract
Acute stress is regulated through the sympathetic adrenergic axis where catecholamines mobilize energy stores including carbohydrates as a principal element of the endocrine stress response. Leptin is a cytokine critical for regulating energy expenditure in vertebrates and is stimulated by various stressors in fish such as fasting, hyperosmotic challenge, and hypoxia. However, little is known about the regulatory interactions between leptin and the endocrine stress axis in fishes and other ectothermic vertebrates. We evaluated the actions of epinephrine and glucose in regulating leptin A (LepA) in vivo and in vitro in tilapia. Using hepatocyte incubations and a homologous LepA ELISA, we show that LepA synthesis and secretion decline as ambient glucose levels increase (10-25 mM). By contrast, bolus glucose administration in tilapia increases lepa mRNA levels 14-fold at 6 h, suggesting systemic factors regulated by glucose may counteract the direct inhibitory effects of glucose on hepatic lepa mRNA observed in vitro. Epinephrine stimulated glucose and LepA secretion from hepatocytes in a dose-dependent fashion within 15 min but had little effect on lepa mRNA levels. An in vivo injection of epinephrine into tilapia stimulated a rapid rise in blood glucose which was followed by a 4-fold increase in hepatic lepa mRNA levels at 2.5 and 6 h. Plasma LepA was also elevated by 6 h relative to controls. Recombinant tilapia LepA administration in vivo did not have any significant effect on plasma epinephrine levels. The results of this study demonstrate LepA is negatively regulated by rises in extracellular glucose at the level of the hepatocyte but stimulated by hyperglycemia in vivo. Further, epinephrine increases LepA. This, along with previous work demonstrating a hyperglycemic and glycogenolytic effect of LepA in tilapia, suggests that epinephrine may stimulate leptin secretion to augment and fine tune glucose mobilization and homeostasis as part of the integrated, adaptive stress response.
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Affiliation(s)
- Jamie L Mankiewicz
- North Carolina State University, Department of Biological Sciences, Raleigh, NC 27695, USA
| | - Courtney A Deck
- North Carolina State University, Department of Biological Sciences, Raleigh, NC 27695, USA
| | - Jordan D Taylor
- North Carolina State University, Department of Biological Sciences, Raleigh, NC 27695, USA
| | - Jonathan D Douros
- Duke University, Molecular Physiology Institute, Durham, NC 27701, USA
| | - Russell J Borski
- North Carolina State University, Department of Biological Sciences, Raleigh, NC 27695, USA.
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Allahyari S, Chaji M, Mamuie M. Investigation changes in production, some blood hormones, and metabolites, serum and colostrum IgG of calves of Holstein cows fed with two levels of zinc supplement in transitional period. JOURNAL OF APPLIED ANIMAL RESEARCH 2019. [DOI: 10.1080/09712119.2019.1653301] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Affiliation(s)
- Sina Allahyari
- Department of Animal Science, Faculty of Animal Science and Food Technology, Agricultural Sciences and Natural Resources University of Khuzestan, Mollasani, Ahvaz, Iran
| | - Morteza Chaji
- Department of Animal Science, Faculty of Animal Science and Food Technology, Agricultural Sciences and Natural Resources University of Khuzestan, Mollasani, Ahvaz, Iran
| | - Morteza Mamuie
- Department of Animal Science, Faculty of Animal Science and Food Technology, Agricultural Sciences and Natural Resources University of Khuzestan, Mollasani, Ahvaz, Iran
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Deck CA, Honeycutt JL, Cheung E, Reynolds HM, Borski RJ. Assessing the Functional Role of Leptin in Energy Homeostasis and the Stress Response in Vertebrates. Front Endocrinol (Lausanne) 2017; 8:63. [PMID: 28439255 PMCID: PMC5384446 DOI: 10.3389/fendo.2017.00063] [Citation(s) in RCA: 49] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2017] [Accepted: 03/23/2017] [Indexed: 12/14/2022] Open
Abstract
Leptin is a pleiotropic hormone that plays a critical role in regulating appetite, energy metabolism, growth, stress, and immune function across vertebrate groups. In mammals, it has been classically described as an adipostat, relaying information regarding energy status to the brain. While retaining poor sequence conservation with mammalian leptins, teleostean leptins elicit a number of similar regulatory properties, although current evidence suggests that it does not function as an adipostat in this group of vertebrates. Teleostean leptin also exhibits functionally divergent properties, however, possibly playing a role in glucoregulation similar to what is observed in lizards. Further, leptin has been recently implicated as a mediator of immune function and the endocrine stress response in teleosts. Here, we provide a review of leptin physiology in vertebrates, with a particular focus on its actions and regulatory properties in the context of stress and the regulation of energy homeostasis.
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Affiliation(s)
- Courtney A. Deck
- Department of Biological Sciences, North Carolina State University, Raleigh, NC, USA
| | - Jamie L. Honeycutt
- Department of Biological Sciences, North Carolina State University, Raleigh, NC, USA
| | - Eugene Cheung
- Department of Biological Sciences, North Carolina State University, Raleigh, NC, USA
| | - Hannah M. Reynolds
- Department of Biological Sciences, North Carolina State University, Raleigh, NC, USA
| | - Russell J. Borski
- Department of Biological Sciences, North Carolina State University, Raleigh, NC, USA
- *Correspondence: Russell J. Borski,
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Nowroozi-Asl A, Aarabi N, Rowshan-Ghasrodashti A. Ghrelin and its correlation with leptin, energy related metabolites and thyroidal hormones in dairy cows in transitional period. Pol J Vet Sci 2016; 19:197-204. [DOI: 10.1515/pjvs-2016-0024] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
AbstractThe transition from late gestation to early lactation is a critical period in a dairy cow’s life so that dairy cows undergo tremendous changes during this period.The aim of this study was to determine blood levels of ghrelin, leptin, glucose, β-ydroxybutyrate (BHB), non-esterified fatty acids (NEFA), triglycerides (TG), triiodothyronine (T3) and thyroxine (T4) in dairy Holstein cows (n = 20) and their correlations during the transition period.Blood samples were collected weekly from 3 wk antepartum to 6 wk postpartum from 20 high-yielding Holstein-Friesian cows. Ghrelin and leptin of plasma and glucose, BHB, NEFA, TG, T3, T4 of serum were then measured.Early lactation cows showed significantly higher (p<0.05) values of ghrelin, BHB and NEFA, and lower levels of leptin, TG, T3 and T4 (p<0.05) compared to late dry cows. Serum concentrations of glucose did not differ significantly at any time (P>0.05).Plasma ghrelin concentrations showed positive correlations with the serum BHB and NEFA (p<0.01), while plasma ghrelin had negative correlations (p<0.01) with leptin, TG, T3 and T4. In addition, no significant correlation (p>0.05) was found between ghrelin and glucose.The results of the study showed that blood ghrelin, leptin, BHB and NEFA levels are sensitive indicators of the energy balance during the peri-partum period in dairy cows and glucose values may not be considered as a precise indicator of negative energy balance in dairy cows.
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Borer KT. Counterregulation of insulin by leptin as key component of autonomic regulation of body weight. World J Diabetes 2014; 5:606-629. [PMID: 25317239 PMCID: PMC4138585 DOI: 10.4239/wjd.v5.i5.606] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2013] [Revised: 05/15/2014] [Accepted: 06/03/2014] [Indexed: 02/05/2023] Open
Abstract
A re-examination of the mechanism controlling eating, locomotion, and metabolism prompts formulation of a new explanatory model containing five features: a coordinating joint role of the (1) autonomic nervous system (ANS); (2) the suprachiasmatic (SCN) master clock in counterbalancing parasympathetic digestive and absorptive functions and feeding with sympathetic locomotor and thermogenic energy expenditure within a circadian framework; (3) interaction of the ANS/SCN command with brain substrates of reward encompassing dopaminergic projections to ventral striatum and limbic and cortical forebrain. These drive the nonhomeostatic feeding and locomotor motivated behaviors in interaction with circulating ghrelin and lateral hypothalamic neurons signaling through melanin concentrating hormone and orexin-hypocretin peptides; (4) counterregulation of insulin by leptin of both gastric and adipose tissue origin through: potentiation by leptin of cholecystokinin-mediated satiation, inhibition of insulin secretion, suppression of insulin lipogenesis by leptin lipolysis, and modulation of peripheral tissue and brain sensitivity to insulin action. Thus weight-loss induced hypoleptimia raises insulin sensitivity and promotes its parasympathetic anabolic actions while obesity-induced hyperleptinemia supresses insulin lipogenic action; and (5) inhibition by leptin of bone mineral accrual suggesting that leptin may contribute to the maintenance of stability of skeletal, lean-body, as well as adipose tissue masses.
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Alvarez-Aguilar C, Alvarez-Paredes AR, Lindholm B, Stenvinkel P, García-López E, Mejía-Rodríguez O, López-Meza JE, Amato D, Paniagua R. Effects of dopamine on leptin release and leptin gene (OB) expression in adipocytes from obese and hypertensive patients. Int J Nephrol Renovasc Dis 2013; 6:259-68. [PMID: 24348062 PMCID: PMC3849084 DOI: 10.2147/ijnrd.s50664] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND A reduction of dopaminergic (DAergic) activity with increased prolactin levels has been found in obese and hypertensive patients, suggesting its involvement as a pathophysiological mechanism promoting hypertension. Similarly, leptin action increasing sympathetic activity has been proposed to be involved in mechanisms of hypertension. The aim of this study was to analyze the effects of DA, norepinephrine (NE), and prolactin on leptin release and leptin gene (OB) expression in adipocytes from obese and hypertensive patients. METHODS Leptin release and OB gene expression were analyzed in cultured adipocytes from 16 obese and hypertensive patients treated with DA (0.001, 0.01, 0.1, and 1.0 μmol/L), NE (1.0 μmol/L), insulin (0.1 μmol/L), and prolactin (1.0 μmol/L), and from five nonobese and normotensive controls treated with DA (1 μmol/L), NE (1 μmol/L), insulin (0.1 μmol/L), and prolactin (1.0 μmol/L). RESULTS A dose-related reduction of leptin release and OB gene messenger ribonucleic acid expression under different doses of DA was observed in adipocytes from obese hypertensive patients. Whereas prolactin treatment elicited a significant increase of both leptin release and OB gene expression, NE reduced these parameters. Although similar effects of DA and NE were observed in adipocytes from controls, baseline values in controls were reduced to 20% of the value in adipocytes from obese hypertensive patients. CONCLUSION These results suggest that DAergic deficiency contributes to metabolic disorders linked to hyperleptinemia in obese and hypertensive patients.
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Affiliation(s)
- Cleto Alvarez-Aguilar
- Hospital General Regional N°1, Instituto Mexicano del Seguro Social (IMSS), Morelia, México ; Facultad de Ciencias Médicas y Biológicas "Dr. Ignacio Chávez" Universidad Michoacana de San Nicolás de Hidalgo (UMSNH), Morelia, Michoacán, México ; División de Estudios Superiores, Universidad Nacional Autónoma de México (UNAM), México DF, México
| | - Alfonso Rafael Alvarez-Paredes
- Facultad de Ciencias Médicas y Biológicas "Dr. Ignacio Chávez" Universidad Michoacana de San Nicolás de Hidalgo (UMSNH), Morelia, Michoacán, México
| | - Bengt Lindholm
- Department of Clinical Science Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Peter Stenvinkel
- Department of Clinical Science Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Elvia García-López
- Department of Clinical Science Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
| | | | - Joel Edmundo López-Meza
- Centro Multidisciplinario de Estudios en Biotecnología (CMEB), UMSNH, Morelia, Michoacán, México
| | - Dante Amato
- Facultad de Estudios Superiores Iztacala, UNAM, Tlalnepantla, México
| | - Ramon Paniagua
- Unidad de Investigación en Enfermedades Nefrológicas, Hospital de Especialidades, CMN Siglo XXI, IMSS, México DF, México
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Wolsk E, Mygind H, Grøndahl TS, Pedersen BK, van Hall G. Human skeletal muscle releases leptin in vivo. Cytokine 2012; 60:667-73. [DOI: 10.1016/j.cyto.2012.08.021] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2012] [Revised: 08/21/2012] [Accepted: 08/23/2012] [Indexed: 01/27/2023]
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Calorie restriction with a high-fat diet effectively attenuated inflammatory response and oxidative stress-related markers in obese tissues of the high diet fed rats. Mediators Inflamm 2012; 2012:984643. [PMID: 22778500 PMCID: PMC3388520 DOI: 10.1155/2012/984643] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2011] [Revised: 02/19/2012] [Accepted: 03/07/2012] [Indexed: 01/03/2023] Open
Abstract
Obesity characterized by increased mass of adipose tissue leads to systemic inflammation. Calorie restriction (CR) improves parameters associated with immune response and antioxidant defense. We hypothesized that CR with a high fat diet (HFCR) regulates local and systemic inflammation and oxidative stress damage in a high fat diet induced obesity (HF group). We investigated effect of HFCR on inflammation and oxidative stress-related markers in liver and adipose tissues as well as adipokines in plasma. HFCR lowered liver triglyceride levels, total cholesterol levels, and the plasma leptin/adiponectin ratio to normal levels and improved glucose tolerance. HFCR also improved fatty liver and normalized adipocyte size and morphology. HFCR reduced lipid peroxidation and decreased the expression levels of inducible nitric oxide synthetase, cyclooxygenase-2, NF-E2-related factor, and heme oxygenase-1 in the liver. Moreover, HFCR suppressed the expression levels of C- reactive protein and manganese superoxide dismutase in the adipose tissue in the HF group. These results suggest that HFCR may have beneficial effects on inflammation and oxidative stress as well as lipid profiles in the HF diet induced obesity. Moreover, HFCR may be a good way to increase compliance in obese patients and to prevent obesity induced complications without changes in dietary pattern.
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Copeland DL, Duff RJ, Liu Q, Prokop J, Londraville RL. Leptin in teleost fishes: an argument for comparative study. Front Physiol 2011; 2:26. [PMID: 21716655 PMCID: PMC3117194 DOI: 10.3389/fphys.2011.00026] [Citation(s) in RCA: 68] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2011] [Accepted: 05/27/2011] [Indexed: 12/13/2022] Open
Abstract
All organisms face tradeoffs with regard to how limited energy resources should be invested. When is it most favorable to grow, to reproduce, how much lipid should be allocated to storage in preparation for a period of limited resources (e.g., winter), instead of being used for growth or maturation? These are a few of the high consequence fitness "decisions" that represent the balance between energy acquisition and allocation. Indeed, for animals to make favorable decisions about when to grow, eat, or reproduce, they must integrate signals among the systems responsible for energy acquisition, storage, and demand. We make the argument that leptin signaling is a likely candidate for an integrating system. Great progress has been made understanding the leptin system in mammals, however our understanding in fishes has been hampered by difficulty in cloning fish orthologs of mammalian proteins and (we assert), underutilization of the comparative approach.
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Modan-Moses D, Kanety H, Dagan O, Ehrlich S, Lotan D, Pariente C, Novikov I, Paret G. Leptin and the post-operative inflammatory response. More insights into the correlation with the clinical course and glucocorticoid administration. J Endocrinol Invest 2010; 33:701-6. [PMID: 20386086 DOI: 10.1007/bf03346673] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/01/2009] [Indexed: 12/19/2022]
Abstract
BACKGROUND Cardiac surgery involving cardiopulmonary bypass (CPB) causes a systemic inflammatory process which can lead to multiple organ failure and postoperative morbidity. Recent animal and human studies suggested a possible involvement of leptin in the systemic inflammatory response. AIM To characterize the response of leptin to open heart surgery (OHS) and the relationship between the time course of leptin levels and the post-operative clinical course, and to examine the effect of exogenous glucocorticoids. PATIENTS AND METHODS Forty-seven pediatric patients, undergoing OHS for congenital heart disease were studied. Thirty-four patients (Group 1) received methylprednisolone during CPB while 13 (group 2) did not. Serial blood samples were collected perioperatively and up to 24 h after surgery, and assayed for leptin and cortisol. RESULTS All patients' leptin levels decreased significantly during CPB (to 44-48% of baseline, p<0.001); they then increased, peaking at 12 h post-operatively. The levels of groups 1 and 2 were similar up to 8 h post-operatively; thereafter, those of group 1 were significantly higher. Recovery of leptin levels in patients with a more complicated post-operative course was comparatively slower. Cortisol levels of all patients increased significantly during CPB (p<0.001), gradually decreasing afterwards. Cortisol and leptin levels were inversely correlated in both patients' groups. CONCLUSIONS CPB is associated with acute changes in circulating leptin levels. A complicated postoperative course is associated with lower leptin levels which are inversely correlated with cortisol levels. Leptin may participate in post-CPB inflammatory and hemodynamic responses.
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Affiliation(s)
- D Modan-Moses
- Pediatric Endocrinology Unit, the Edmond and Lily Safra Children's Hospital, Tel Aviv, Israel.
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13
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Goossens GH, Jocken JWE, van Baak MA, Jansen EHJM, Saris WHM, Blaak EE. Short-term beta-adrenergic regulation of leptin, adiponectin and interleukin-6 secretion in vivo in lean and obese subjects. Diabetes Obes Metab 2008; 10:1029-38. [PMID: 18435774 DOI: 10.1111/j.1463-1326.2008.00856.x] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
AIM Adipose tissue and skeletal muscle are endocrine organs, secreting substances that have been implicated in obesity-related disorders. This study examined short-term beta-adrenergic regulation of circulating leptin, adiponectin and interleukin-6 (IL-6) concentrations and secretion from abdominal subcutaneous adipose tissue and muscle (IL-6) in vivo in lean and obese subjects. METHODS Systemic concentrations and net fluxes of leptin, adiponectin and IL-6 across abdominal subcutaneous adipose tissue and forearm skeletal muscle (IL-6) were assessed before and during beta-adrenergic stimulation (intravenous isoprenaline infusion) in 13 lean and 10 obese men. RESULTS Basal circulating leptin concentrations were higher in the obese (p < 0.001), while circulating adiponectin (p = 0.45) and IL-6 concentrations (p = 0.41) were not different between groups. beta-Adrenergic stimulation decreased leptin concentrations in both groups (p < 0.01), but did not reduce net abdominal subcutaneous adipose tissue leptin release. Increased leptin clearance and/or decreased leptin secretion from other fat depots may explain the reduction in leptin concentrations. Adiponectin concentrations remained unchanged during beta-adrenergic stimulation in both groups. beta-Adrenergic stimulation increased IL-6 concentration, which was more pronounced in the obese (p = 0.01 vs. lean). This cannot be explained by increased IL-6 release per unit abdominal subcutaneous adipose tissue and muscle but might be because of the increased fat mass and fat-free mass at whole-body level. CONCLUSIONS Short-term beta-adrenergic stimulation decreases leptin concentrations, which cannot be explained by reduced net leptin release from abdominal subcutaneous adipose tissue, while it elevates IL-6 concentration partly by increased release from this fat depot and muscle. Finally, beta-adrenergic stimulation has no short-term regulatory role in adiponectin secretion.
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Affiliation(s)
- G H Goossens
- Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, Maastricht, The Netherlands.
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14
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Kraus T, Reulbach U, Bayerlein K, Mugele B, Hillemacher T, Sperling W, Kornhuber J, Bleich S. Leptin is associated with craving in females with alcoholism. Addict Biol 2006. [DOI: 10.1111/j.1369-1600.2004.tb00535.x] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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15
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Ceballos RM, Faraday MM, Cousino Klein L. Rat Strain and Sex Differences in Leptin Responses to Immobilization Stress. JOURNAL OF INDIVIDUAL DIFFERENCES 2006. [DOI: 10.1027/1614-0001.27.3.136] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
The effects of immobilization (IM) stress on plasma leptin levels and bodyweight in adult Sprague-Dawley (19 males, 20 females) and Long-Evans (20 males, 20 females) rats were investigated. Following a 10-day baseline period, half the animals from each experimental group were exposed to immobilization stress or no-stress 20 min/day for 21 days. Plasma leptin and corticosterone levels were measured following stress or no-stress exposure on the last day of the experiment. Corticosterone levels confirmed stress exposure. Important interactive effects of stress, strain, and sex on leptin and corticosterone levels were also observed. Specifically, females displayed higher leptin levels than did males, regardless of stress exposure. Strain interacted with stress such that stressed Long-Evans rats displayed higher leptin levels than did stressed Sprague-Dawley rats; there were no strain differences in leptin levels among nonstressed rats. Also, correlations between leptin and corticosterone were strain-specific. Results are discussed with respect to previously unreported strain differences in the effects of immobilization stress on circulating plasma leptin and the relevance to inconsistent findings in the human literature.
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Affiliation(s)
- Rachel M. Ceballos
- Department of Health Services, University of Washington, Seattle, WA, USA
| | - Martha M. Faraday
- Data Management Services, Inc., National Cancer Center Institute at Frederick, Frederick, MD, USA
| | - Laura Cousino Klein
- Department of Biobehavioral Health, Center for Developmental and Health Genetics, The Pennsylvania State University, University Park, PA, USA
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16
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Keller P, Keller C, Steensberg A, Robinson LE, Pedersen BK. Leptin gene expression and systemic levels in healthy men: effect of exercise, carbohydrate, interleukin-6, and epinephrine. J Appl Physiol (1985) 2005; 98:1805-12. [PMID: 15640395 DOI: 10.1152/japplphysiol.00592.2004] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Leptin, an adipose tissue-derived cytokine, is correlated with adipose mass as obese persons have increased levels of leptin that decrease with weight loss. Previous studies demonstrate that high-energy-expenditure exercise decreases circulating leptin levels, whereas low-energy-expenditure exercise has no effect. We aimed to test the hypothesis that acute exercise reduced leptin mRNA levels in human adipose tissue and that this effect would be ameliorated by carbohydrate supplementation. Because exercise markedly increases circulating IL-6 and epinephrine, we investigated whether the changes in leptin seen with acute exercise could be mediated by IL-6 or epinephrine infusion. Abdominal subcutaneous adipose tissue mRNA and plasma levels of leptin were measured in healthy men in response to 3-h ergometer exercise with or without carbohydrate (CHO) ingestion ( n = 8) and in response to infusion with recombinant human (rh)IL-6 ( n = 11) or epinephrine ( n = 8) or saline. Plasma leptin declined in response to exercise ( P < 0.05) compared with rest, whereas mRNA expression in adipose tissue was unaffected. The exercise-induced decrease in plasma leptin was attenuated by CHO ingestion ( P < 0.001). A 3-h epinephrine infusion decreased plasma leptin ( P < 0.001) to the same level seen with 3 h of exercise, whereas leptin levels were unaffected by rhIL-6 infusion. In conclusion, both acute exercise and epinephrine infusion decreased plasma leptin to a similar extent, whereas there was no effect with rhIL-6 infusion. Acute exercise solely affected leptin plasma levels, as mRNA levels were unchanged. The exercise-induced decrease in circulating leptin was counteracted by CHO ingestion, suggesting a posttranscriptional regulatory mechanism of leptin involving substrate availability.
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Affiliation(s)
- Pernille Keller
- Centre of Inflammation and Metabolism, Department of Infectious Diseases and The Copenhagen Muscle Research Center, Faculty of Health Sciences, University Hospital of Copenhagen, Denmark
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17
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Ricci MR, Lee MJ, Russell CD, Wang Y, Sullivan S, Schneider SH, Brolin RE, Fried SK. Isoproterenol decreases leptin release from rat and human adipose tissue through posttranscriptional mechanisms. Am J Physiol Endocrinol Metab 2005; 288:E798-804. [PMID: 15585586 DOI: 10.1152/ajpendo.00446.2004] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
In vivo and in vitro studies indicate that beta-adrenergic receptor agonists decrease leptin release from fat cells in as little as 30 min. Our objective was to determine whether alterations in leptin biosynthesis or secretion were involved in the short-term adrenergic regulation of leptin in human and rat adipose tissue. Isoproterenol (Iso) decreased leptin release from incubated adipose tissue of both nonobese and obese subjects to similar extent (-28 vs. -21% after 3 h). Inhibition of protein synthesis with cycloheximide did not block the effect of Iso on leptin release from human adipose tissue, suggesting that the Iso effect is independent of leptin synthesis. Iso also tended to increase tissue leptin content at the end of the 3-h incubation, as expected from the observed inhibition of release. Consistent with a posttranslational mechanism, Iso treatment did not affect leptin mRNA levels or relative rate of leptin biosynthesis as directly assessed by [35S]methionine incorporation into immunoprecipitable leptin. In contrast to these results in human adipose tissues, Iso did not decrease basal leptin release from rat adipose tissue. However, Iso did decrease insulin-stimulated leptin release by inhibiting the ability of insulin to increase leptin biosynthesis without detectably affecting leptin mRNA levels. Thus, in both human and rat, adrenergic regulation of posttranscriptional events (secretion in humans, translation in rats) may contribute to the rapid decline in circulating leptin that occurs when the sympathetic nervous system is activated, such as during fasting and cold exposure. Furthermore, the rat does not provide an ideal model to study mechanisms of cellular leptin regulation in humans.
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Affiliation(s)
- Matthew R Ricci
- Department of Nutritional Sciences, Rutgers Univeristy, New Brunswick, New Jersey, USA
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18
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Chu CP, Qiu DL, Kato K, Kunitake T, Watanabe S, Yu NS, Nakazato M, Kannan H. Central stresscopin modulates cardiovascular function through the adrenal medulla in conscious rats. ACTA ACUST UNITED AC 2004; 119:53-9. [PMID: 15093697 DOI: 10.1016/j.regpep.2003.12.007] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2003] [Revised: 12/26/2003] [Accepted: 12/29/2003] [Indexed: 10/26/2022]
Abstract
Stresscopin (SCP or urocortin III), a member of the corticotropin-releasing factor (CRF) neuropeptide family, is a high-affinity ligand for the type 2 CRF receptor (CRF(2)). When administered peripherally, SCP suppresses food intake, delays gastric emptying and decreases heat-induced edema. Central administration of CRF produces marked hypertension and increased plasma catecholamine. However, the effects of SCP on the cardiovascular system are unknown. Thus, the present study compared the effects of intracerebroventricular (i.c.v.) administration of CRF and SCP on cardiovascular function. Central administration of SCP (0.05 or 0.5 nmol) elicited transient increases in mean arterial blood pressure (MABP) and heart rate (HR), and the higher dose of SCP (0.5 nmol) resulted in increased plasma epinephrine. In contrast, central administration of CRF provoked long-lasting increases in MABP, HR and plasma catecholamine levels (norepinephrine and epinephrine). Intravenously administered CRF and SCP (0.5 nmol) did not elicit significant changes in MABP and HR. Therefore, these data suggest that centrally administered SCP modulates cardiovascular function, likely through the sympatho-adrenal-medullary (SAM) system.
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Affiliation(s)
- Chun-Ping Chu
- Department of Physiology, Miyazaki Medical College, 5200 Kihara, Kiyotake-cho, Miyazaki-gun, Miyazaki 889-1692, Japan
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19
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Tsofliou F, Pitsiladis YP, Malkova D, Wallace AM, Lean MEJ. Moderate physical activity permits acute coupling between serum leptin and appetite–satiety measures in obese women. Int J Obes (Lond) 2003; 27:1332-9. [PMID: 14574343 DOI: 10.1038/sj.ijo.0802406] [Citation(s) in RCA: 37] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
OBJECTIVES To investigate whether moderate physical activity or snack intake influence appetite sensations and subsequent food intake in obese women. Associations between serum leptin and appetite ratings were also investigated. METHODS In all, 10 obese women (mean age+/-s.d.: 50.0+/-8.5 y; mean body mass index (BMI)+/-s.d.: 37.2+/-6.5 kg m(-2)) were submitted in random order to three trials: Moderate physical activity (20 min brisk walking), Snack (58.5 g chocolate-based) and Control (sitting, TV-watching). Appetite and satiety were assessed by visual analogue scales, and serum leptin, blood glucose and plasma free fatty acids were measured at baseline, pre- and postintervention and 1 h postintervention (ie, before dinner). A buffet-style dinner was provided subsequent to the three trials. RESULTS The moderate physical activity and snack intake both produced lower appetite and higher satiety and fullness perceptions, compared to control, following the intervention. No significant differences were found in subsequent food intake. Serum leptin concentrations did not differ between trials. Serum leptin was not associated with appetite or satiety sensations at any time during the control or the snack trials, but was correlated following moderate physical activity (prospective food consumption r(s)=-0.83, P=0.003; hunger r(s)=-0.79, P=0.007; desire to eat r(s)=-0.69, P=0.02; satiety r(s)=0.71, P=0.02; fullness r(s)=0.66, P=0.04). These associations were not influenced by BMI or fat mass. CONCLUSIONS Moderate physical activity and snack intake suppress the appetite of obese women acutely. The associations between circulating leptin and appetite-satiety ratings suggest leptin involvement in short-term appetite regulation in response to physical activity-induced factors.
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Affiliation(s)
- F Tsofliou
- Human Nutrition at Glasgow, Division of Developmental Medicine, University of Glasgow, Glasgow Royal Infirmary, Glasgow, Scotland
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20
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Atmaca M, Kuloglu M, Tezcan E, Ustundag B. Serum leptin and cholesterol levels in schizophrenic patients with and without suicide attempts. Acta Psychiatr Scand 2003; 108:208-14. [PMID: 12890276 DOI: 10.1034/j.1600-0447.2003.00145.x] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
OBJECTIVE Previous studies demonstrate a relationship between lipid metabolism and suicide or impulsive-aggressive behaviours. Leptin seems to be related with lipid metabolism. Therefore, the aim was to measure total serum cholesterol and leptin levels in 16 medication-free schizophrenic patients with and without suicide attempts and in 16 healthy controls. METHOD Subjects were assessed by using Impulsivity Rating (IRS) and Modified Overt Aggression Scale (MOAS). RESULTS The patients had lower total cholesterol and leptin levels in serum compared with the controls. Significantly lower total cholesterol and leptin levels were observed in patients who had attempted suicide compared with those who had not. The levels were observed to be low in violent attempters when compared with non-violent attempters. MOAS and IRS scores were negatively correlated with both cholesterol or leptin levels in patients. CONCLUSION The results indicated that medication-free schizophrenic patients have statistically significant lower serum cholesterol and leptin levels compared with controls and the difference is obvious in suicide attempters compared with non-suicide attempters and in violent attempters than non-violent attempters.
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Affiliation(s)
- M Atmaca
- Departments of Psychiatry and Clinical Biochemistry, Firat University, School of Medicine, Elazig, Turkey.
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21
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Eikelis N, Schlaich M, Aggarwal A, Kaye D, Esler M. Interactions between leptin and the human sympathetic nervous system. Hypertension 2003; 41:1072-9. [PMID: 12668587 DOI: 10.1161/01.hyp.0000066289.17754.49] [Citation(s) in RCA: 193] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Results from animal experimentation suggest a 2-way interaction between leptin and the sympathetic nervous system, with leptin causing sympathetic activation and conversely, with the sympathetic system exercising regulatory feedback inhibition over leptin release. We have now tested this hypothesis in humans. In the absence of results from leptin infusions, to test for sympathetic stimulation of leptin release, we sought a quantitative naturalistic linkage of sympathetic activity with leptin plasma concentration across a broad range of leptin values in men of widely differing adiposity. Renal norepinephrine spillover was correlated with plasma leptin (r=0.628, P<0.01), but other measures of sympathoadrenal function did not. To test for sympathetic and adrenomedullary inhibition of leptin release, we studied clinical models of high sympathetic tone, heart failure, and essential hypertension, in which lowered plasma leptin levels might have been expected but were not found; a model of low sympathetic activity, pure autonomic failure, in which plasma leptin level was normal (6.1+/-1.2 vs 12.8+/-3.1 ng/mL in healthy subjects); and a clinical model of reduced epinephrine secretion, healthy aging, in which plasma leptin level again was normal (5.7+/-1.1 ng/mL vs 4.0+/-0.9 ng/mL in men >60 years and <35 years, respectively). Paradoxically, leptin concentration was elevated in heart failure, caused entirely by reduced renal clearance of leptin release, 142.0+/-30.5 mL/min, compared with 56.9+/-18.9 mL/min (P<0.05). These results provide some support for the view that leptin stimulates the sympathetic nervous system, at least for renal sympathetic outflow, but do not confirm the concept of regulatory feedback inhibition of leptin release by the sympathetic nervous system.
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Affiliation(s)
- Nina Eikelis
- Baker Heart Research Institute and Alfred Baker Medical Unit, Alfred Hospital, Melbourne, Australia
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22
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Jeon JY, Harber VJ, Steadward RD. Leptin response to short-term fasting in sympathectomized men: role of the SNS. Am J Physiol Endocrinol Metab 2003; 284:E634-40. [PMID: 12556356 DOI: 10.1152/ajpendo.00302.2002] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
We studied plasma leptin levels in six people with high-lesion spinal cord injury [SCI; body mass index (BMI) 25.9 +/- 1.5 kg/m(2), age 37 +/- 3.0 yr] and six able-bodied (AB) controls (BMI 29.1 +/- 1.9 kg/m(2), age 35 +/- 3.5 yr) before and after 12, 24, and 36 h of fasting. The plasma leptin levels significantly decreased during 36 h fasting by 48.8 +/- 4.5% (pre: 11.3 +/- 2.3, post: 6.2 +/- 1.5 ng/ml) and 38.6 +/- 7.9% (pre: 7.6 +/- 5.0, post: 4.2 +/- 1.0 ng/ml) in SCI and AB, respectively. Plasma leptin started to decrease at 24 h of fasting in the SCI group, whereas plasma leptin started to decrease at 12 h of fasting in the AB group. The current study demonstrated that plasma leptin decreased with fasting in both SCI and AB groups, with the leptin decrease being delayed in the SCI group. The delayed leptin response to fasting in the SCI group may be because of increased fat mass (%body fat, SCI: 33.8 +/- 3.0, AB: 24.1 +/- 2.9) and sympathetic nervous system dysfunction.
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Affiliation(s)
- Justin Y Jeon
- The Steadward Center for Personal and Physical Achievement, Department of Physical Education and Recreation, University of Alberta, Edmonton, Alberta, Canada T6G 2H9.
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Mark AL, Rahmouni K, Correia M, Haynes WG. A leptin-sympathetic-leptin feedback loop: potential implications for regulation of arterial pressure and body fat. ACTA PHYSIOLOGICA SCANDINAVICA 2003; 177:345-9. [PMID: 12609005 DOI: 10.1046/j.1365-201x.2003.01085.x] [Citation(s) in RCA: 52] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
AIM This manuscript briefly reviews evidence and potential implications of a leptin-sympathetic-leptin feedback loop. RESULTS Leptin increases sympathetic nerve activity to brown adipose tissue, kidney and other tissues. This action has implications for regulation of arterial pressure. In turn, there is evidence that sympathoadrenal stimulation inhibits leptin mRNA expression and secretion from white adipose tissue through beta adrenergic mechanisms. CONCLUSION This sympathetic modulation of leptin expression has potential implications for regulation of body fat.
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Affiliation(s)
- A L Mark
- Specialized Center of Research in Hypertension Genetics, the Department of Internal Medicine, Lucille A Carver College of Medicine, and the Veterans Administration Medical Center, Iowa City, IA 52242-1101, USA
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Weise M, Eisenhofer G, Merke DP. Pubertal and gender-related changes in the sympathoadrenal system in healthy children. J Clin Endocrinol Metab 2002; 87:5038-43. [PMID: 12414869 DOI: 10.1210/jc.2002-020590] [Citation(s) in RCA: 49] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
A critical amount of body fat is necessary for the initiation of puberty, and leptin, an adipocyte-derived hormone, is necessary for pubertal development. The sympathoadrenal system modulates body fat stores and leptin secretion and interacts with adrenocortical androgen production, suggesting a possible role in sexual maturation. We studied sympathetic nerve and adrenomedullary activity at rest in 80 healthy children (ages, 5-17 yr; 37 boys and 43 girls) in relation to age, pubertal stage, gender, physical activity, body mass index, and serum levels of sex steroids, dehydroepiandrosterone sulfate, cortisol, leptin, and insulin. Plasma concentrations of the adrenomedullary hormone, epinephrine (E), and its metabolite metanephrine (MN), decreased significantly with advancing puberty and were higher in boys than in girls. E and MN correlated significantly and inversely with dehydroepiandrosterone sulfate, estradiol, testosterone, leptin, and insulin. Plasma norepinephrine, which is primarily derived from sympathetic nerve endings, increased significantly with advancing puberty and increasing testosterone levels in boys. Stepwise multiple regression analysis revealed that E was best predicted by pubertal stage and leptin, and MN by estradiol and leptin. Our data suggest that sympathoadrenal hormones may play a role in the complex process of sexual maturation. Further studies are needed to investigate a possible modulatory role of the adrenal medulla in the body weight-related timing of adrenarche and/or gonadarche.
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Affiliation(s)
- Martina Weise
- Developmental Endocrinology Branch, National Institute of Child Health and Human Development/NIH, Building 10, 10 Center Drive, Bethesda, MD 20892-1932, USA
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Abstract
Short-term exercise (<60 min) studies suggest that leptin concentrations are not acutely affected in healthy males and females. Most reports of reductions in serum leptin may be attributed to circadian rhythms or hemoconcentration. For long-term (> or =60 min) exercise, a reduction in leptin concentrations reported from 1 to 3 hr of running or cycling has been attributed to diurnal reduction in circulating leptin, independent of exercise. Exercise that produces a sufficient energy imbalance (kilocalorie intake versus kilocalorie expenditure) suppresses 24-hr mean and amplitude of the diurnal rhythm of leptin in women. Suppression of leptin concentrations may be counterbalanced by feeding and may explain consistent reports of reductions in leptin concentrations following extreme bouts of exercise such as marathons or ultramarathons. In addition, leptin concentrations are reduced 48 hr after long-term aerobic exercise and long-term resistance exercise is associated with delayed leptin reduction 9 hr postexercise. Training studies have documented that short-term exercise training (< or =12 weeks) does not affect leptin levels, with the exception of patients with type 2 diabetes. Exercise training protocols that result in reduced fat mass will lower leptin concentrations, thus, most investigators have reported leptin concentrations after accounting for fat loss. There are disparate findings concerning long-term (>12 weeks) training studies, with a number of studies finding no effect of training on leptin concentrations other than effects induced by fat loss, and other studies finding reductions in leptin concentrations after accounting for fat loss. Exercise training-induced reductions in leptin levels have been attributed to alterations in energy balance, improvements in insulin sensitivity, alterations in lipid metabolism, and unknown factors. Hormone replacement does not seem to affect leptin adaptations to training. Patients with type 2 diabetes show delayed effects of short-term resistance exercise on leptin concentrations, reduced leptin levels with long-term training, and appear to be more sensitive to training-induced leptin adaptations than other populations.
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Affiliation(s)
- Robert R Kraemer
- Department of Kinesiology and Health Studies, Southeastern Louisiana University, Hammond 70402, USA.
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Vicennati V, Vottero A, Friedman C, Papanicolaou DA. Hormonal regulation of interleukin-6 production in human adipocytes. Int J Obes (Lond) 2002; 26:905-11. [PMID: 12080442 DOI: 10.1038/sj.ijo.0802035] [Citation(s) in RCA: 84] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2001] [Revised: 02/19/2002] [Accepted: 02/25/2002] [Indexed: 12/20/2022]
Abstract
OBJECTIVE To elucidate the hormonal regulation of interleukin-6 (IL-6) production by human adipose tissue and its relation to leptin. DESIGN In vitro study. Human adipocytes were incubated with dexamethasone (with or without RU486), norepinephrine and epinephrine (with or without propranolol), or insulin. MEASUREMENTS IL-6 and leptin secretion by human adipocytes. RESULTS A gradual increase in IL-6 secretion by adipocytes during differentiation was observed. A positive correlation was found between basal IL-6 release and both glycerol 3-phosphate dehydrogenase activity--a marker of adipocyte differentiation-and leptin release. Dexamethasone decreased IL-6 secretion and increased leptin secretion in a dose-dependent manner. Both catecholamines increased IL-6 and leptin secretion. The effects of dexamethasone and catecholamines on IL-6 and leptin were abrogated by RU486 and propranolol, respectively. Incubation with insulin resulted in a dose-dependent stimulation of IL-6 and leptin secretion. CONCLUSIONS IL-6 is produced by human adipocytes and is a potential marker of adipocyte differentiation. Furthermore it is a hormonally regulated cytokine, suppressed by glucocorticoids, and stimulated by catecholamines and insulin in physiological concentrations.
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Affiliation(s)
- V Vicennati
- Endocrine Unit, S. Orsola Hospital, University of Bologna, Bologna, Italy
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Couillard C, Mauriège P, Prud'homme D, Nadeau A, Tremblay A, Bouchard C, Després JP. Plasma leptin response to an epinephrine infusion in lean and obese women. OBESITY RESEARCH 2002; 10:6-13. [PMID: 11786596 DOI: 10.1038/oby.2002.2] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
OBJECTIVE Because leptin production by adipose tissue is under hormonal control, we examined the impact of epinephrine administration on plasma leptin concentrations. RESEARCH METHODS AND PROCEDURES We measured plasma leptin, insulin, and free fatty acid (FFA) responses after a 60-minute epinephrine infusion (0.010 microg/kg fat free mass/min) followed by a 30-minute recovery period (no infusion) in a group of 11 lean (mean body mass index +/- SD: 22.6 +/- 1.1 kg/m(2)) and 15 obese (30.0 +/- 1.3 kg/m(2)) premenopausal women. Leptin, insulin, and FFA levels were measured in plasma before (-15 and 0 minutes) and at every 30 minutes over the 90-minute period. RESULTS In both lean and obese individuals, plasma leptin was significantly reduced by epinephrine (p < 0.0001). Body fat mass was associated with fasting leptin levels (r = 0.64, p < 0.0005) as well as with the decrease in leptinemia (r = -0.51, p < 0.01) produced by epinephrine administration. Furthermore, we noted a large range of leptin response to epinephrine among our subjects, especially in obese women (from -12 to -570 ng/mL per 60 minutes). However, there was no association between postepinephrine leptin and FFA levels (r = -0.14, p = 0.55). DISCUSSION Results of this study indicate that leptin levels decrease after epinephrine administration in both lean and obese premenopausal women. However, the heterogeneity in the response of leptin to catecholamines suggests potential alterations of the leptin axis that may contribute to generate a positive energy balance and, thus, may favor weight gain in some obese individuals.
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Affiliation(s)
- Charles Couillard
- Department of Food Science and Nutrition, Laval University, Sainte-Foy, Québec, Canada
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Verdich C, Toubro S, Buemann B, Holst JJ, Bülow J, Simonsen L, Søndergaard SB, Christensen NJ, Astrup A. Leptin levels are associated with fat oxidation and dietary-induced weight loss in obesity. OBESITY RESEARCH 2001; 9:452-61. [PMID: 11500525 DOI: 10.1038/oby.2001.59] [Citation(s) in RCA: 42] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
OBJECTIVE To examine the relationship between fasting plasma leptin and 24-hour energy expenditure (EE), substrate oxidation, and spontaneous physical activity (SPA) in obese subjects before and after a major weight reduction compared with normal weight controls. To test fasting plasma leptin, substrate oxidations, and SPA as predictive markers of success during a standardized weight loss intervention. RESEARCH METHODS AND PROCEDURES Twenty-one nondiabetic obese (body mass index: 33.9 to 43.8 kg/m(2)) and 13 lean (body mass index: 20.4 to 24.7 kg/m(2)) men matched for age and height were included in the study. All obese subjects were reexamined after a mean weight loss of 19.2 kg (95% confidence interval: 15.1-23.4 kg) achieved by 16 weeks of dietary intervention followed by 8 weeks of weight stability. Twenty-four-hour EE and substrate oxidations were measured by whole-body indirect calorimetry. SPA was assessed by microwave radar. RESULTS In lean subjects, leptin adjusted for fat mass (FM) was correlated to 24-hour EE before (r = -0.56, p < 0.05) but not after adjustment for fat free mass. In obese subjects, leptin correlated inversely with 24-hour and resting nonprotein respiratory quotient (r = -0.47, p < 0.05 and r = -0.50, p < 0.05) both before and after adjustments for energy balance. Baseline plasma leptin concentration, adjusted for differences in FM, was inversely related to the size of weight loss after 8 weeks (r = -0.41, p = 0.07), 16 weeks (r = -0.51, p < 0.05), and 24 weeks (r = -0.50, p < 0.05). DISCUSSION The present study suggests that leptin may have a stimulating effect on fat oxidation in obese subjects. A low leptin level for a given FM was associated with a greater weight loss, suggesting that obese subjects with greater leptin sensitivities are more successful in reducing weight.
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Affiliation(s)
- C Verdich
- Research Department of Human Nutrition, Centre for Food Research, The Royal Veterinary and Agricultural University, DK-1958 Frederiksberg C, Denmark
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Fujimaki S, Kanda T, Fujita K, Tamura J, Kobayashi I. The significance of measuring plasma leptin in acute myocardial infarction. J Int Med Res 2001; 29:108-13. [PMID: 11393343 DOI: 10.1177/147323000102900207] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
We measured leptin concentrations in patients with acute myocardial infarction (AMI, n = 21) and in 15 age-matched controls, and compared leptin concentrations with levels of other myocardial enzymes and indicators of AMI. Blood was sampled immediately after hospital admission and at 1 h, 2 h, 3 h, 6 h and 9 h, then every 12 h until 5 days post-admission. Patients were stratified into three groups according to peak leptin concentrations: hypoleptinaemia (< 3 ng/ml); normoleptinaemia (> or = 3 - < 15 ng/ml) and hyperleptinaemia (> or = 15 ng/ml). Hypoleptinaemic AMI patients had significantly increased concentrations of plasma lactate dehydrogenase compared with normoleptinaemic patients. No significant differences in other serum markers were noted between hyperleptinaemic and normoleptinaemic AMI patients. A significant negative correlation was found between the peak concentrations of leptin and interleukin 6. Leptin may play a role in the regulation of the development of cardiac damage in patients with AMI.
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Affiliation(s)
- S Fujimaki
- Department of General Medicine, Gunma University School of Medicine, Maebashi, Japan
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Montalbán C, Del Moral I, García-Unzueta MT, Villanueva MA, Amado JA. Perioperative response of leptin and the tumor necrosis factor alpha system in morbidly obese patients. Influence of cortisol inhibition by etomidate. Acta Anaesthesiol Scand 2001; 45:207-12. [PMID: 11167167 DOI: 10.1034/j.1399-6576.2001.450212.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
BACKGROUND Leptin, tumor necrosis factor alpha (TNFalpha) and soluble TNFalpha receptors are secreted by the adipose tissue. Surgery induces a complex cytokine and neurohormonal response. The aim of our study was to investigate the perioperative response of leptin and the TNFalpha system in morbidly obese patients submitted to gastroplasty, and the possible involvement of cortisol in their responses. METHODS Serum cortisol, adrenocorticotropic hormone (ACTH), leptin, TNFalpha and soluble TNFalpha receptor I were measured in 22 morbidly obese women (11 anesthetized with thiopental and 11 with etomidate, a well known inhibitor of cortisol synthesis). Samples were collected before anesthesia induction, just before surgical incision, and 2, 4, 6, 12, 24 and 48 h after the start of surgery. RESULTS Baseline serum leptin correlated with body mass index (r=0.567, P=0.007). Baseline serum leptin and TNFalpha were higher than normal. Cortisol release was inhibited in the etomidate group with a subsequent higher stimulation of ACTH release. A statistically significant decrease in serum leptin levels was observed in both groups at 2, 4, 6 and 48 h, compared with basal values. A similar decrease in serum TNFalpha levels was observed in both groups, but the decrease reached significance only in the etomidate group. Serum soluble TNFalpha receptor I did not decrease. No differences were found between the two groups in leptin, TNFalpha or soluble TNFalpha receptor I concentrations at any time. CONCLUSION Serum leptin and TNFalpha levels decrease in obese patients during gastroplasty. Transitory inhibition of cortisol release does not alter this response.
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Affiliation(s)
- C Montalbán
- Endocrine Unit, Hospital Universitario Marqués de Valdecilla, University of Cantabria, Santander, Spain
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Abstract
Serum levels of the adipocyte hormone leptin are increased in proportion to body fat stores as a result of increased production in enlarged fat cells from obese subjects. In vitro studies indicate that insulin and glucocorticoids work directly on adipose tissue to upregulate in a synergistic manner leptin mRNA levels and rates of leptin secretion in human adipose tissue over the long term. Thus, the increased leptin expression observed in obesity could result from the chronic hyperinsulinemia and increased cortisol turnover. Superimposed upon the long-term regulation, nutritional status can influence serum leptin over the short term, independent of adiposity. Fasting leads to a gradual decline in serum leptin that is probably attributable to the decline in insulin and the ability of catecholamines to decrease leptin expression, as observed in both in vivo and in vitro studies. In addition, increases in serum leptin occur approximately 4-7 h after meals. Increasing evidence indicates that insulin, in concert with permissive effects of cortisol, can increase serum leptin over this time frame and likely contributes to meal-induced increases in serum leptin. Further research is required to elucidate the cellular and molecular mechanisms underlying short- and long-term nutritional and hormonal regulation of leptin production and secretion.
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Affiliation(s)
- S K Fried
- Department of Nutritional Sciences, Rutgers University, New Brunswick, NJ 08901, USA
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