title: Ghrelin action in the brain controls adipocyte metabolism.
abstract: Many homeostatic processes, including appetite and food intake, are controlled by neuroendocrine circuits involving the CNS. The CNS also directly regulates adipocyte metabolism, as we have shown here by examining central action of the orexigenic hormone ghrelin. Chronic central ghrelin infusion resulted in increases in the glucose utilization rate of white and brown adipose tissue without affecting skeletal muscle. In white adipocytes, mRNA expression of various fat storage-promoting enzymes such as lipoprotein lipase, acetyl-CoA carboxylase alpha, fatty acid synthase, and stearoyl-CoA desaturase-1 was markedly increased, while that of the rate-limiting step in fat oxidation, carnitine palmitoyl transferase-1alpha, was decreased. In brown adipocytes, central ghrelin infusion resulted in lowered expression of the thermogenesis-related mitochondrial uncoupling proteins 1 and 3. These ghrelin effects were dose dependent, occurred independently from ghrelin-induced hyperphagia, and seemed to be mediated by the sympathetic nervous system. Additionally, the expression of some fat storage enzymes was decreased in ghrelin-deficient mice, which led us to conclude that central ghrelin is of physiological relevance in the control of cell metabolism in adipose tissue. These results unravel the existence of what we believe to be a new CNS-based neuroendocrine circuit regulating metabolic homeostasis of adipose tissue.
authors.affiliation: Laboratory of Metabolism, Division of Endocrinology, Diabetology, and Nutrition, Department of Internal Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Claudia
authors.initials: C
authors.lastname: Theander-Carrillo
authors.forename: Petra
authors.initials: P
authors.lastname: Wiedmer
authors.forename: Philippe
authors.initials: P
authors.lastname: Cettour-Rose
authors.forename: Ruben
authors.initials: R
authors.lastname: Nogueiras
authors.forename: Diego
authors.initials: D
authors.lastname: Perez-Tilve
authors.forename: Paul
authors.initials: P
authors.lastname: Pfluger
authors.forename: Tamara R
authors.initials: TR
authors.lastname: Castaneda
authors.forename: Patrick
authors.initials: P
authors.lastname: Muzzin
authors.forename: Annette
authors.initials: A
authors.lastname: Schürmann
authors.forename: Ildiko
authors.initials: I
authors.lastname: Szanto
authors.forename: Matthias H
authors.initials: MH
authors.lastname: Tschöp
authors.forename: Françoise
authors.initials: F
authors.lastname: Rohner-Jeanrenaud
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000235:genetics / Q000378:metabolism; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D064429:Fatty Acid Synthases / Q000235:genetics / Q000378:metabolism; D054439:Ghrelin; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D007473:Ion Channels; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D024101:Mitochondrial Proteins; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism; D036361:Peptide Hormones / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013230:Stearoyl-CoA Desaturase / Q000235:genetics / Q000378:metabolism; D000071256:Uncoupling Protein 1; D000071247:Uncoupling Protein 3
chemical_list: D002352:Carrier Proteins; D054439:Ghrelin; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D009478:Neuropeptide Y; D036361:Peptide Hormones; D000071256:Uncoupling Protein 1; D000071247:Uncoupling Protein 3; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase; D064429:Fatty Acid Synthases; D008071:Lipoprotein Lipase; D000103:Acetyl-CoA Carboxylase; D005947:Glucose