title: Corticotropin-releasing hormone-mediated pathway of leptin to regulate feeding, adiposity, and uncoupling protein expression in mice.
abstract: To examine the functional role of CRH in the regulation of energy homeostasis by leptin, we measured the effects of the CRH antagonist, alpha-helical CRH 8-41 (alphaCRH) on a number of factors affected by leptin activity. These included food intake, body weight, hypothalamic c-fos-like immunoreactivity (c-FLI), weight and histological characterization of white adipose tissue, and mRNA expressions of uncoupling protein (UCP) in brown adipose tissue (BAT) in C57Bl/6 mice. Central infusion of leptin into the lateral cerebroventricle (icv) caused significant induction of c-FLI in the paraventricular nucleus (PVN), ventromedial hypothalamic nucleus (VMH), dorsomedial hypothalamic nucleus, and arcuate nucleus. In all these nuclei, the effect of leptin on expression of cFLI in the PVN and VMH was decreased by treatment with alphaCRH. Administration of leptin markedly decreased cumulative food intake and body weight with this effect being attenuated by pretreatment with alphaCRH. In peripheral tissue, leptin up-regulated BAT UCP1 mRNA expression and reduced fat depositions in this tissue. Those changes in BAT were also decreased by treatment with alphaCRH. As a consequence of the effects on food intake or energy expenditure, treatment with alphaCRH attenuated the leptin-induced reduction of body adiposity, fat cell size, triglyceride contents, and ob mRNA expression in white adipose tissue. Taken together, these results indicate that CRH neurons in the PVN and VMH may be an important mediator for leptin that contribute to regulation of feeding, adiposity, and UCP expression.
authors.affiliation: Department of Internal Medicine, School of Medicine, Oita Medical University, Oita 879-5593, Japan. masaki@oita-med.ac.jp
authors.forename: Takayuki
authors.initials: T
authors.lastname: Masaki
authors.forename: Go
authors.initials: G
authors.lastname: Yoshimichi
authors.forename: Seiichi
authors.initials: S
authors.lastname: Chiba
authors.forename: Tohru
authors.initials: T
authors.lastname: Yasuda
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Noguchi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kakuma
authors.forename: Toshiie
authors.initials: T
authors.lastname: Sakata
authors.forename: Hironobu
authors.initials: H
authors.lastname: Yoshimatsu
mesh_terms: D017667:Adipocytes / Q000166:cytology; D000273:Adipose Tissue / Q000737:chemistry; D002001:Adipose Tissue, Brown / Q000033:anatomy & histology / Q000737:chemistry; D000818:Animals; D001823:Body Composition / Q000187:drug effects; D002352:Carrier Proteins / Q000235:genetics*; D048429:Cell Size / Q000187:drug effects; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D004435:Eating / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006706:Homeostasis; D006727:Hormone Antagonists / Q000494:pharmacology; D007031:Hypothalamus / Q000737:chemistry / Q000187:drug effects; D007473:Ion Channels; D020738:Leptin / Q000008:administration & dosage / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D014280:Triglycerides / Q000032:analysis; D000071256:Uncoupling Protein 1
chemical_list: D002352:Carrier Proteins; D006727:Hormone Antagonists; D007473:Ion Channels; D020738:Leptin; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D014280:Triglycerides; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; C069206:alpha helical corticotropin-releasing hormone; D003346:Corticotropin-Releasing Hormone