Journal article
Central Melanin-Concentrating Hormone Influences Liver and Adipose Metabolism Via Specific Hypothalamic Nuclei and Efferent Autonomic/JNK1 Pathways
Gastroenterology (New York, N.Y. 1943), Vol.144(3), pp.636-649.e6
03/2013
DOI: 10.1053/j.gastro.2012.10.051
PMCID: PMC3663042
PMID: 23142626
Abstract
Specific neuronal circuits modulate autonomic outflow to liver and white adipose tissue. Melanin-concentrating hormone (MCH)-deficient mice are hypophagic, lean, and do not develop hepatosteatosis when fed a high-fat diet. Herein, we sought to investigate the role of MCH, an orexigenic neuropeptide specifically expressed in the lateral hypothalamic area, on hepatic and adipocyte metabolism.
Chronic central administration of MCH and adenoviral vectors increasing MCH signaling were performed in rats and mice. Vagal denervation was performed to assess its effect on liver metabolism. The peripheral effects on lipid metabolism were assessed by real-time polymerase chain reaction and Western blot.
We showed that the activation of MCH receptors promotes nonalcoholic fatty liver disease through the parasympathetic nervous system, whereas it increases fat deposition in white adipose tissue via the suppression of sympathetic traffic. These metabolic actions are independent of parallel changes in food intake and energy expenditure. In the liver, MCH triggers lipid accumulation and lipid uptake, with c-Jun N-terminal kinase being an essential player, whereas in adipocytes MCH induces metabolic pathways that promote lipid storage and decreases lipid mobilization. Genetic activation of MCH receptors or infusion of MCH specifically in the lateral hypothalamic area modulated hepatic lipid metabolism, whereas the specific activation of this receptor in the arcuate nucleus affected adipocyte metabolism.
Our findings show that central MCH directly controls hepatic and adipocyte metabolism through different pathways.
Details
- Title: Subtitle
- Central Melanin-Concentrating Hormone Influences Liver and Adipose Metabolism Via Specific Hypothalamic Nuclei and Efferent Autonomic/JNK1 Pathways
- Creators
- Monica Imbernon - Department of Physiology, School of Medicine, University of Santiago de Compostela-Instituto de Investigación Sanitaria, S. Francisco s/n, Santiago de Compostela (A Coruña), SpainDaniel Beiroa - Department of Physiology, School of Medicine, University of Santiago de Compostela-Instituto de Investigación Sanitaria, S. Francisco s/n, Santiago de Compostela (A Coruña), SpainMaría J Vázquez - Department of Physiology, School of Medicine, University of Santiago de Compostela-Instituto de Investigación Sanitaria, S. Francisco s/n, Santiago de Compostela (A Coruña), SpainDonald A Morgan - Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IowaChristelle Veyrat–Durebex - Laboratory of Metabolism, Division of Endocrinology, Diabetology and Nutrition, Department of Internal Medicine, Faculty of Medicine, University of Geneva, Geneva, SwitzerlandBegoña Porteiro - Department of Physiology, School of Medicine, University of Santiago de Compostela-Instituto de Investigación Sanitaria, S. Francisco s/n, Santiago de Compostela (A Coruña), SpainAdenis Díaz–Arteaga - Department of Physiology, School of Medicine, University of Santiago de Compostela-Instituto de Investigación Sanitaria, S. Francisco s/n, Santiago de Compostela (A Coruña), SpainAna Senra - Department of Physiology, School of Medicine, University of Santiago de Compostela-Instituto de Investigación Sanitaria, S. Francisco s/n, Santiago de Compostela (A Coruña), SpainSilvia Busquets - Department of Biochemistry and Molecular Biology, University of Barcelona, Barcelona, SpainDouglas A Velásquez - Department of Physiology, School of Medicine, University of Santiago de Compostela-Instituto de Investigación Sanitaria, S. Francisco s/n, Santiago de Compostela (A Coruña), SpainOmar Al–Massadi - Centro de Investigación Biomédica en Red (CIBER) Fisiopatología de la Obesidad y Nutrición, Santiago de Compostela, SpainLuis Varela - Department of Physiology, School of Medicine, University of Santiago de Compostela-Instituto de Investigación Sanitaria, S. Francisco s/n, Santiago de Compostela (A Coruña), SpainMarina Gándara - Department of Morphological Sciences, School of Medicine, University of Santiago de Compostela-Instituto de Investigación Sanitaria, S. Francisco s/n, Santiago de Compostela (A Coruña), SpainFrancisco–Javier López–Soriano - Department of Biochemistry and Molecular Biology, University of Barcelona, Barcelona, SpainRosalía Gallego - Department of Morphological Sciences, School of Medicine, University of Santiago de Compostela-Instituto de Investigación Sanitaria, S. Francisco s/n, Santiago de Compostela (A Coruña), SpainLuisa M Seoane - Centro de Investigación Biomédica en Red (CIBER) Fisiopatología de la Obesidad y Nutrición, Santiago de Compostela, SpainJosep M Argiles - Department of Biochemistry and Molecular Biology, University of Barcelona, Barcelona, SpainMiguel López - Department of Physiology, School of Medicine, University of Santiago de Compostela-Instituto de Investigación Sanitaria, S. Francisco s/n, Santiago de Compostela (A Coruña), SpainRoger J Davis - Howard Hughes Medical Institute, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MassachusettsGuadalupe Sabio - Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, SpainFrançoise Rohner–Jeanrenaud - Laboratory of Metabolism, Division of Endocrinology, Diabetology and Nutrition, Department of Internal Medicine, Faculty of Medicine, University of Geneva, Geneva, SwitzerlandKamal Rahmouni - Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IowaCarlos Dieguez - Department of Physiology, School of Medicine, University of Santiago de Compostela-Instituto de Investigación Sanitaria, S. Francisco s/n, Santiago de Compostela (A Coruña), SpainRuben Nogueiras - Department of Physiology, School of Medicine, University of Santiago de Compostela-Instituto de Investigación Sanitaria, S. Francisco s/n, Santiago de Compostela (A Coruña), Spain
- Resource Type
- Journal article
- Publication Details
- Gastroenterology (New York, N.Y. 1943), Vol.144(3), pp.636-649.e6
- Publisher
- Elsevier Inc
- DOI
- 10.1053/j.gastro.2012.10.051
- PMID
- 23142626
- PMCID
- PMC3663042
- ISSN
- 0016-5085
- eISSN
- 1528-0012
- Grant note
- HL084207 / US National Institutes of Health PS09/01880 / Fondo Investigationes Sanitarias 245009; ERC-2010-StG-OBECAN-260464; ERC-2011-StG-OBESITY53-281408 / European Community's Seventh Framework Programme BFU2011; RyC-2007-00211; RYC-2008-02219; SAF2009-07049; RYC-2009-04972; SAF2010-19347 / Ministerio de Educacion y Ciencia 1-11-BS-127 / American Diabetes Association 31003A-134919/1 / Swiss National Science Foundation 10PXIB208164PR; 2010/14 / Xunta de Galicia
- Language
- English
- Date published
- 03/2013
- Academic Unit
- Iowa Neuroscience Institute; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040459502771
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