Abstract P193: Angiotensin-(1-7) Acutely Induces Browning of White Adipose Tissue in Mice

Abstract

Angiotensin (Ang)-(1-7) is a beneficial hormone of the renin-angiotensin system that is emerging as a promising target for obesity. We previously showed that chronic Ang-(1-7) treatment attenuates high fat diet (HFD)-induced weight gain in mice by increasing markers of thermogenesis in subcutaneous white adipose tissue (“browning”) to increase energy expenditure. In this study, we tested the hypothesis that Ang-(1-7) could acutely increase adipose thermogenesis in mice. To test this, adult male C57BL/6J mice were placed on a chow diet or 60% HFD for 12 weeks and then received a single subcutaneous injection of Ang-(1-7) (2mg/kg) or saline. This study included 4 groups of mice: chow+saline (n=9), chow+Ang-(1-7) (n=15), HFD+saline (n=8), HFD+Ang-(1-7) (n=10). Core temperature was measured at baseline and at 6 hours after injection. Subcutaneous white and brown adipose tissues were collected 6 hours post-injection. Gene expression of the thermogenic marker uncoupling protein 1 (UCP1) was measured in tissues by quantitative real-time PCR and quantified with 2-ΔΔCT methods. Acutely, Ang-(1-7) did not alter body mass in chow or HFD mice ( P= 0.992). There were 5 chow fed mice (33%) and 2 HFD mice (20%) that did not respond to Ang-(1-7) injection. In the chow diet responders, Ang-(1-7) increased core temperature (36.7±0.2 vs 35.9±0.2°C saline; P =0.012) and UCP1 gene expression in subcutaneous white adipose tissue (14.3±5.8 vs 1.9±0.6 saline; P =0.050), with no effect in brown adipose tissue (1.7±0.6 vs 1.0±0.2 saline, P =0.284). In the HFD responders, core temperature was not altered by Ang-(1-7) (37.8±0.1 vs 37.8±0.1 saline, P =0.689). There was a trend towards decreased UCP1 expression in white adipose of HFD-saline mice compared to chow-saline mice ( P =0.196). Ang-(1-7) significantly increased UCP1 expression in subcutaneous white adipose of HFD responders (6.2±3.1 vs 0.9±0.2 saline, P =0.036), with no effect in brown adipose tissue (1.2±0.1 vs saline: 1.7±0.4 saline, P =0.402). These data provide further evidence that targeting Ang-(1-7) may be a promising strategy to increase white adipose thermogenesis, an effect that could serve to enhance energy expenditure and restore energy balance in obesity.