Littlejohn Nicole K, Keen Henry L, Weidemann Benjamin J, Claflin Kristin E, Tobin Kevin V, Markan Kathleen R, Park Sungmi, Naber Meghan C, Gourronc Francoise A, Pearson Nicole A, Liu Xuebo, Morgan Donald A, Klingelhutz Aloysius J, Potthoff Matthew J, Rahmouni Kamal, Sigmund Curt D, Grobe Justin L
Department of Pharmacology, University of Iowa, Iowa City, IA 52242, USA.
Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA.
Cell Rep. 2016 Aug 9;16(6):1548-1560. doi: 10.1016/j.celrep.2016.07.003. Epub 2016 Jul 28.
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.
脑肾素-血管紧张素系统（RAS）的激活通过提高静息代谢率（RMR）来刺激能量消耗，而这一效应需要同时抑制循环和/或脂肪组织中的RAS。为了确定外周RAS对抗脑RAS对RMR控制的机制，我们研究了脑RAS转基因激活的小鼠（sRA小鼠）。sRA小鼠通过腹股沟脂肪组织中能量通量的增加表现出RMR升高，而这种效应会被2型血管紧张素II受体（AT2）激活所减弱。腹股沟脂肪细胞中的AT2激活对抗去甲肾上腺素诱导的解偶联蛋白-1（UCP1）产生以及细胞呼吸的某些方面，但不影响脂肪分解。AT2激活也对抗腹股沟脂肪细胞功能以及对表皮生长因子（EGF）的分化反应。这些结果突出了腹股沟脂肪细胞内AT2在RMR控制中的主要多方面作用。因此，AT2受体可能有助于身体脂肪分布以及脂肪储存部位对心脏代谢健康的特异性影响。
