Activation of angiotensin type 2 receptor rescues high‐fat dietinduced adipocyte size increase in young male mice

Abstract

Recent studies demonstrated that genetic deletion of angiotensin type 2 receptor (AT2R) decreases adipocyte size and controls obesity, a major risk factor for metabolic syndromes. Current study was designed to test whether pharmacological manipulation of AT2R regulates adipocyte size. Male C57BL/6 mice (4‐weeks old) were pretreated with AT2R antagonist (PD‐123319, 30 μg/kg/min, osmotic pump) or AT2‐R agonist (C21, 0.3 mg/kg, daily i.p.) for 4 days. Thereafter the animals were placed on normal chow diet (ND) or high‐fat diet (HFD) with concurrent drugs treatment for next 10 days. The PD treatment increased the ratio of total abdominal fat weight to body weight in both ND and HFD groups compared with the respective controls. Similarly, the PD treatment caused increase in epididymal fat weight in both ND and HFD. Epididymal adipocyte size was also increased in HFD group treated with PD. On the other hand, C21 treatment rescued HFD‐induced increase in epididymal fat weight and adipocyte size. The HFD‐induced increase in plasma free fatty acid level was prevented by C21 treatment. In sum, pharmacological blocking of AT2R increases and activation of AT2R decreases adipocyte size. This is the first study which demonstrates that adipocyte size increase is rescued by the pharmacological activation of AT2R, which may serve as therapeutic target for controlling obesity and associated disorders.Grant Funding Source : NIH RO1 DK‐61578