Mechanism of action of BRS-3 in temperature regulation

Thursday, October 11, 2012 — Poster Session III
10:00 a.m. – Noon	Natcher Conference Center, Building 45	NIDDK	ENDOC-10

Authors

• D.M. Lateef
• C Xiao
• O Cheng
• M.L. Reitman

Abstract

Bombesin receptor subtype-3 (Brs3) is an orphan G-protein coupled receptor found in brain sites that are implicated in temperature regulation. Bombesin receptor subtype-3 (Brs3) knockout (KO) mice exhibit an obese phenotype and lower body temperatures compared to their wild type counterparts, and synthetic BRS-3 agonists have been shown to increase body temperature in wild type mice, rats and dogs. However, the mechanism underlying the role of BRS-3 in temperature regulation remains unknown. Here we examined the effect of MK-5046, a synthetic BRS-3 agonist, on the brown adipose tissue (BAT) thermogenesis. We found that MK-5046 (1mg/kg) increased temperature in BAT of anesthetized wild type but not Brs3 KO mice. CL-316,243, a selective beta-3 adrenoceptor agonist, increased BAT and body temperature in wild type and KO mice, suggesting an intact beta-3 receptor in Brs3 KO mice. Ambulatory Brs3 KO mice also exhibited lower BAT temperatures compared to wild type controls. These results demonstrate that MK-5046 increases body temperature, at least in part, by activating BAT, presumably through a sympathetic pathway.

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