Angiotensin AT(1A) receptors on leptin receptor-expressing cells control resting metabolism

作者：Claflin Kristin E; Sandgren Jeremy A; Lambertz Allyn M; Weidemann Benjamin J; Littlejohn Nicole K; Burnett Colin M L; Pearson Nicole A; Morgan Donald A; Gibson Corley Katherine N; Rahmouni Kamal; Grobe Justin L

来源：Journal of Clinical Investigation, 2017, 127(4): 1414-1424.

DOI：10.1172/JCI88641

Leptin contributes to the control of resting metabolic rate (RMR) and blood pressure (BP) through its actions in the arcuate nucleus (ARC). The renin-angiotensin system (RAS) and angiotensin AT(1) receptors within the brain are also involved in the control of RMR and BP, but whether this regulation overlaps with leptin's actions is unclear. Here, we have demonstrated the selective requirement of the AT(1A) receptor in leptin-mediated control of RMR. We observed that AT(1A) receptors colocalized with leptin receptors (LEPRs) in the ARC. Cellular coexpression of AT(1A) and LEPR was almost exclusive to the ARC and occurred primarily within neurons expressing agouti-related peptide (AgRP). Mice lacking the AT(1A) receptor specifically in LEPR-expressing cells failed to show an increase in RMR in response to a high-fat diet and deoxycorticosterone acetate-salt (DOCA-salt) treatments, but BP control remained intact. Accordingly, loss of RMR control was recapitulated in mice lacking AT(1A) in AgRP-expressing cells. We conclude that angiotensin activates divergent mechanisms to control BP and RMR and that the brain RAS functions as a major integrator for RMR control through its actions at leptin-sensitive AgRP cells of the ARC.

• 出版日期2017-4-3