| First Author | Yamamoto R | Year | 2011 |
| Journal | J Biol Chem | Volume | 286 |
| Issue | 24 | Pages | 21458-65 |
| PubMed ID | 21525005 | Mgi Jnum | J:173644 |
| Mgi Id | MGI:5049832 | Doi | 10.1074/jbc.M110.192260 |
| Citation | Yamamoto R, et al. (2011) Angiotensin II Type 1 Receptor Signaling Regulates Feeding Behavior through Anorexigenic Corticotropin-releasing Hormone in Hypothalamus. J Biol Chem 286(24):21458-65 |
| abstractText | 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. |
