title: Angiotensin II type 1 receptor signaling regulates feeding behavior through anorexigenic corticotropin-releasing hormone in hypothalamus.
abstract: The activation of renin-angiotensin system contributes to the development of metabolic syndrome and diabetes as well as hypertension. However, it remains undetermined how renin-angiotensin system is implicated in feeding behavior. Here, we show that angiotensin II type 1 (AT(1)) receptor signaling regulates the hypothalamic neurocircuit that is involved in the control of food intake. Compared with wild-type Agtr1a(+/+) mice, AT(1) receptor knock-out (Agtr1a(-/-)) mice were hyperphagic and obese with increased adiposity on an ad libitum diet, whereas Agtr1a(-/-) mice were lean with decreased adiposity on a pair-fed diet. In the hypothalamus, mRNA levels of anorexigenic neuropeptide corticotropin-releasing hormone (Crh) were lower in Agtr1a(-/-) mice than in Agtr1a(+/+) mice both on an ad libitum and pair-fed diet. Furthermore, intracerebroventricular administration of CRH suppressed food intake both in Agtr1a(+/+) and Agtr1a(-/-) mice. In addition, the Crh gene promoter was significantly transactivated via the cAMP-responsive element by angiotensin II stimulation. These results thus demonstrate that central AT(1) receptor signaling plays a homeostatic role in the regulation of food intake by maintaining gene expression of Crh in hypothalamus and suggest a therapeutic potential of central AT(1) receptor blockade in feeding disorders.
authors.affiliation: Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, Chiba, Chiba 260-8670, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Yamamoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Akazawa
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Fujihara
authors.forename: Yukako
authors.initials: Y
authors.lastname: Ozasa
authors.forename: Noritaka
authors.initials: N
authors.lastname: Yasuda
authors.forename: Kaoru
authors.initials: K
authors.lastname: Ito
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kudo
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Qin
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ueta
authors.forename: Issei
authors.initials: I
authors.lastname: Komuro
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D005247:Feeding Behavior; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D007031:Hypothalamus / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009479:Neuropeptides / Q000737:chemistry; D009765:Obesity / Q000378:metabolism; D009842:Oligopeptides / Q000737:chemistry; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*
chemical_list: D009479:Neuropeptides; D009842:Oligopeptides; D044140:Receptor, Angiotensin, Type 1; C023866:pyroglutamyl-histidyl-glycine; D003346:Corticotropin-Releasing Hormone; D011761:Pyrrolidonecarboxylic Acid