title: Central melanin-concentrating hormone influences liver and adipose metabolism via specific hypothalamic nuclei and efferent autonomic/JNK1 pathways.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Our findings show that central MCH directly controls hepatic and adipocyte metabolism through different pathways.
authors.affiliation: 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.
authors.forename: Monica
authors.initials: M
authors.lastname: Imbernon
authors.forename: Daniel
authors.initials: D
authors.lastname: Beiroa
authors.forename: María J
authors.initials: MJ
authors.lastname: Vázquez
authors.forename: Donald A
authors.initials: DA
authors.lastname: Morgan
authors.forename: Christelle
authors.initials: C
authors.lastname: Veyrat-Durebex
authors.forename: Begoña
authors.initials: B
authors.lastname: Porteiro
authors.forename: Adenis
authors.initials: A
authors.lastname: Díaz-Arteaga
authors.forename: Ana
authors.initials: A
authors.lastname: Senra
authors.forename: Silvia
authors.initials: S
authors.lastname: Busquets
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Velásquez
authors.forename: Omar
authors.initials: O
authors.lastname: Al-Massadi
authors.forename: Luis
authors.initials: L
authors.lastname: Varela
authors.forename: Marina
authors.initials: M
authors.lastname: Gándara
authors.forename: Francisco-Javier
authors.initials: FJ
authors.lastname: López-Soriano
authors.forename: Rosalía
authors.initials: R
authors.lastname: Gallego
authors.forename: Luisa M
authors.initials: LM
authors.lastname: Seoane
authors.forename: Josep M
authors.initials: JM
authors.lastname: Argiles
authors.forename: Miguel
authors.initials: M
authors.lastname: López
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Davis
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Sabio
authors.forename: Françoise
authors.initials: F
authors.lastname: Rohner-Jeanrenaud
authors.forename: Kamal
authors.initials: K
authors.lastname: Rahmouni
authors.forename: Carlos
authors.initials: C
authors.lastname: Dieguez
authors.forename: Ruben
authors.initials: R
authors.lastname: Nogueiras
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D050154:Adiposity / Q000502:physiology*; D000818:Animals; D004435:Eating; D005227:Fatty Acids / Q000378:metabolism; D005234:Fatty Liver / Q000378:metabolism / Q000503:physiopathology; D007026:Hypothalamic Area, Lateral / Q000187:drug effects / Q000502:physiology*; D007028:Hypothalamic Hormones / Q000008:administration & dosage / Q000502:physiology*; D050356:Lipid Metabolism / Q000187:drug effects / Q000502:physiology; D050155:Lipogenesis / Q000187:drug effects / Q000502:physiology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008543:Melanins / Q000008:administration & dosage / Q000502:physiology*; D051379:Mice; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism*; D065626:Non-alcoholic Fatty Liver Disease; D010907:Pituitary Hormones / Q000008:administration & dosage / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011979:Receptors, Pituitary Hormone / Q000819:agonists / Q000502:physiology; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology
chemical_list: D005227:Fatty Acids; D007028:Hypothalamic Hormones; D008543:Melanins; D010907:Pituitary Hormones; D011979:Receptors, Pituitary Hormone; C092274:melanin-concentrating hormone receptor; C019463:melanin-concentrating hormone; D048055:Mitogen-Activated Protein Kinase 8