Impact of Exercise Training and Enalapril, either alone or in Combination, on White Adipose Tissue Renin‐Angiotensin System in a Diet‐Induced Obesity Model

Abstract

The renin–angiotensin system (RAS) has emerged as a regulator of metabolic homeostasis with angiotensin (Ang) II acting as an ‘adiposity signal’ and Ang 1–7 promoting counter‐regulatory effects. Chronic endurance training profoundly affects white adipose tissue (WAT) metabolism and causes remarkable changes in its RAS. In this context, the aim of this study was to evaluate the effects of endurance training and the angiotensin converting enzyme (ACE) inhibitor enalapril on WAT RAS and adiposity in a diet‐induced obesity mouse model. C57BL/6 mice were fed either standard chow (SC) or high‐fat (HF) diets for 16 weeks. After 8 weeks, HF‐fed animals were divided into 4 groups (n=8): HF, HF + Enalapril (HF‐E), HF + training (HF‐T) and HF + Enalapril + training (HF‐ET). Endurance training consisted of 60 min/day, 5 days/week moderate‐intensity treadmill running. Enalapril (10 mg/kg/day) was administered in the diet. Both interventions were maintained for 8 weeks. We assessed body mass (BM) and composition by DEXA, systolic blood pressure (SBP), lipid and inflammatory profile, circulating irisin, and WAT histology. WAT RAS components were measured by HPLC‐DAD. In comparison to SC animals, BM significantly increased in HF animals, but not in mice subjected to HF‐E and HF‐T interventions, whereas BM was significantly reduced in the HF‐ET group. SBP, adipocyte hypertrophy, adiposity index, and percentage body fat were all elated in HF compared to SC mice; however, the interventions prevented these elevations. Circulating cholesterol levels increased in the HF and HF‐E groups, whereas in the HF‐T and HF‐ET this variable did not differ from the SC group. IL‐6 and TNF‐α were significantly elevated by HF diet, and all interventions reduced circulating levels of these inflammatory markers to values similar to those of SC mice. Plasma irisin was increased only in endurance‐trained mice. WAT Ang II concentration was higher in the HF than SC group and all interventions reduced it. The HF‐ET group showed the lowest Ang II concentration compared to the other groups. The Ang II/Ang 1–7 WAT ratio in HF‐E and HF‐T was similar to the SC mice, whereas in the HF‐ET this ratio was significantly lower than SC and HF groups. The results of this study suggest that enalapril combined with endurance training has better results than either treatment alone in reducing adiposity and shifting the balance of RAS toward the Ang 1–7 counter‐regulatory axis in WAT. Furthermore, both enalapril and endurance training improved the inflammatory profile, although only endurance training reduced cholesterol and increased irisin levels. These results suggest that targeting WAT RAS could be a new therapeutic approach to treat obesity‐related dysfunctional metabolic alteration.Support or Funding InformationFAPERJ, CAPES and CNPqThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.