Captopril intake decreases body weight gain via angiotensin-(1-7).

Angiotensin-(1-7) [Ang-(1-7)] plays a beneficial role in cardiovascular physiology by providing a counterbalance to the function of angiotensin II (Ang II). Although Ang II has been shown to be an adipokine secreted by adipocyte and affect lipid metabolism, the role of Ang-(1-7) in adipose tissue remains to be clarified. The aim of the present study was to investigate whether Ang-(1-7) affects lipid metabolism in adipose tissue. Ang-(1-7) increased glycerol release from primary adipocytes in a dose-dependent manner. A lipolytic effect of Ang-(1-7) was attenuated by pretreatment with A-779, a Mas receptor blocker and with an inhibitor of phosphoinositol 3-kinase (PI3K), or eNOS. However, losartan and PD123319 did not cause any change in Ang-(1-7)-induced lipolysis. Ang-(1-7)-induced lipolysis had an addictive effect with isoproterenol. In normal rats, chronic intake of captopril for 4 wks decreased body weight gain and the amount of adipose tissue and increased plasma Ang-(1-7) level. These effects were attenuated by administration of A-779. The levels of Mas receptor and phosphorylation of hormone-sensitive lipase (p-HSL) were significantly increased by treatment with captopril and these captopril-mediated effects were attenuated by the administration of A-779. There was no difference in diameter of adipocytes among sham, captopril- and captopril+A-779-treated groups. The similar effects of captopril on body weight, expression of Mas receptor, and p-HSL were observed in Ang-(1-7)-treated rats. These results suggest that captopril intake decreased body weight gain partly through Ang-(1-7)/Mas receptor/PI3K pathway.