Faculty Collaboration Database

Angiotensin AT1A receptors on leptin receptor-expressing cells control resting metabolism. J Clin Invest 2017 Apr 03;127(4):1414-1424

Date

03/07/2017

Pubmed ID

28263184

Pubmed Central ID

PMC5373887

DOI

10.1172/JCI88641

Scopus ID

2-s2.0-85018718095 (requires institutional sign-in at Scopus site)   57 Citations

Abstract

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 AT1 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 AT1A receptor in leptin-mediated control of RMR. We observed that AT1A receptors colocalized with leptin receptors (LEPRs) in the ARC. Cellular coexpression of AT1A and LEPR was almost exclusive to the ARC and occurred primarily within neurons expressing agouti-related peptide (AgRP). Mice lacking the AT1A 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 AT1A 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.

Author List

Claflin KE, Sandgren JA, Lambertz AM, Weidemann BJ, Littlejohn NK, Burnett CM, Pearson NA, Morgan DA, Gibson-Corley KN, Rahmouni K, Grobe JL

Author

Justin L. Grobe PhD Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Agouti-Related Protein
Angiotensin II
Animals
Arcuate Nucleus of Hypothalamus
Basal Metabolism
Blood Pressure
Diet, High-Fat
Female
GABAergic Neurons
Leptin
Male
Mice, Inbred C57BL
Mice, Knockout
Pro-Opiomelanocortin
Protein Transport
Receptor, Angiotensin, Type 1
Receptors, Leptin
alpha-MSH