3 years ago

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

Hajime Hosoi, Hisakazu Nakajima, Yasuhiro Kawabe, Yusuke Tsuma, Satoaki Matoba, Shota Fukuhara, Gavin Y Oudit, Jun Mori, Hidechika Morimoto, Kazuki Kodo, Kazuya Ikoma
The renin-angiotensin system is a key regulator of metabolism with beneficial effects of the angiotensin 1-7 peptide. We hypothesized that the anti-obesity effect of Ang 1-7 is related to the stimulation of brown adipose tissue (BAT). We administered Ang 1-7 (0.54 mg・kg(-1)・d(-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 (WAT) 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 (HSL) and decreased expression of perilipin. These data suggests 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 represent a promising therapy to increase BAT and to reduce the metabolic complications associated with diet-induced obesity.

Publisher URL: http://doi.org/10.1152/ajpendo.00192.2017

DOI: 10.1152/ajpendo.00192.2017

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