Angiotensin AT2R activation prevents adiposity under high‐fat diet‐condition in ovariectomized mice

Recently we demonstrated that the genetic deletion of angiotensin AT2 receptor (AT2R) increases adiposity in female mice on high‐fat diet (HFD). Further these changes were associated with decrease in the urinary 17,β‐estradiol (E2), a known regulator of adiposity. This study was designed to test whether AT2R activation prevents adiposity dependent on estrogen. Female C57BL/6 ovariectomized (Ovx) female mice (8‐weeks old) were supplemented with E2 pellets and/or pretreated with AT2R agonist C21 (0.3 mg/kg, daily i.p.) for 4 days. Thereafter the mice were placed on normal diet (ND) or HFD and the drugs treatment continued for next 10 days. Ovx mice had increased body weight (BW), gonadal adipose tissue weight (gATW), plasma free fatty acid (pFFA) compared to mice with intact ovary on ND. High‐fat diet (HFD) in Ovx mice further increased BW, gATW, pFFA. As expected, E2 supplementation prevented the above mentioned parameters under HFD in Ovx mice. Interestingly, C21 treatment alone in Ovx mice significantly prevented BW gain (19%), gATW (42%), pFFA (55%) despite similar energy intake compared to Ovx mice on HFD. We conclude that the pharmacological activation of AT2R alone prevents adiposity in ovariectomized mice indicating estrogen‐independent role of AT2R in preventing HFD‐induced adiposity in females. Grant Funding Source : NIH RO1 DK‐61578