TY - JOUR
T1 - Suppression of Resting Metabolism by the Angiotensin AT2 Receptor
AU - Littlejohn, Nicole K.
AU - Keen, Henry L.
AU - Weidemann, Benjamin J.
AU - Claflin, Kristin E.
AU - Tobin, Kevin V.
AU - Markan, Kathleen R.
AU - Park, Sungmi
AU - Naber, Meghan C.
AU - Gourronc, Francoise A.
AU - Pearson, Nicole A.
AU - Liu, Xuebo
AU - Morgan, Donald A.
AU - Klingelhutz, Aloysius J.
AU - Potthoff, Matthew J.
AU - Rahmouni, Kamal
AU - Sigmund, Curt D.
AU - Grobe, Justin L.
N1 - Publisher Copyright:
© 2016 The Author(s)
PY - 2016/8/9
Y1 - 2016/8/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84979752805&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2016.07.003
DO - 10.1016/j.celrep.2016.07.003
M3 - Article
C2 - 27477281
AN - SCOPUS:84979752805
SN - 2639-1856
VL - 16
SP - 1548
EP - 1560
JO - Cell Reports
JF - Cell Reports
IS - 6
ER -