Angiotensin 1–7 stimulates brown adipose tissue and reduces diet-induced obesity

Abstract

The renin-angiotensin system is a key regulator of metabolism with beneficial effects of the angiotensin 1–7 (Ang 1–7) peptide. We hypothesized that the antiobesity effect of Ang 1–7 was related to the stimulation of brown adipose tissue (BAT). We administered Ang 1–7 (0.54 mg kg -1 day -1 ) for 28 days via implanted micro-osmotic pumps to mice with high-fat diet (HFD)-induced obesity. Ang 1–7 treatment reduced body weight, upregulated thermogenesis, and ameliorated impaired glucose homeostasis without affecting food consumption. Furthermore, Ang 1–7 treatment enlarged BAT and the increased expression of UCP1, PRDM16, and prohibitin. Alterations in PRDM16 expression correlated with increased AMPK and phosphorylation of mTOR. Ang 1–7 treatment elevated thermogenesis in subcutaneous white adipose tissue without altering UCP1 expression. These changes occurred in the context of decreased lipid accumulation in BAT from HFD-fed mice, preserved insulin signaling concomitant with phosphorylation of hormone-sensitive lipase and decreased expression of perilipin. These data suggest that Ang 1–7 induces brown adipocyte differentiation leading to upregulation of thermogenesis and improved metabolic profile in diet-induced obesity. Enhancing Ang 1–7 action represents a promising therapy to increase BAT and to reduce the metabolic complications associated with diet-induced obesity.