Suppression of Resting Metabolism by the Angiotensin AT2 Receptor

Nicole K. Littlejohn, Henry L. Keen, Benjamin J. Weidemann, Kristin E. Claflin, Kevin V. Tobin, Kathleen R. Markan, Sungmi Park, Meghan C. Naber, Francoise A. Gourronc, Nicole A. Pearson, Xuebo Liu, Donald A. Morgan, Aloysius J. Klingelhutz, Matthew J. Potthoff, Kamal Rahmouni, Curt D. Sigmund, Justin L. Grobe

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Activation of the brain renin-angiotensin system (RAS) stimulates energy expenditure through increasing of the resting metabolic rate (RMR), and this effect requires simultaneous suppression of the circulating and/or adipose RAS. To identify the mechanism by which the peripheral RAS opposes RMR control by the brain RAS, we examined mice with transgenic activation of the brain RAS (sRA mice). sRA mice exhibit increased RMR through increased energy flux in the inguinal adipose tissue, and this effect is attenuated by angiotensin II type 2 receptor (AT2) activation. AT2 activation in inguinal adipocytes opposes norepinephrine-induced uncoupling protein-1 (UCP1) production and aspects of cellular respiration, but not lipolysis. AT2 activation also opposes inguinal adipocyte function and differentiation responses to epidermal growth factor (EGF). These results highlight a major, multifaceted role for AT2 within inguinal adipocytes in the control of RMR. The AT2 receptor may therefore contribute to body fat distribution and adipose depot-specific effects upon cardio-metabolic health.

Original languageEnglish
Pages (from-to)1548-1560
Number of pages13
JournalCell Reports
Volume16
Issue number6
DOIs
StatePublished - Aug 9 2016

Fingerprint

Dive into the research topics of 'Suppression of Resting Metabolism by the Angiotensin AT2 Receptor'. Together they form a unique fingerprint.

Cite this