The gene knockout of angiotensin II type 1a receptor improves high-fat diet-induced obesity in rat via promoting adipose lipolysis

Aims The renin-angiotensin system (RAS) is over-activated and the serum angiotensin II (Ang II) level increased in obese patients, while their correlations were incompletely understood. This study aims to explore the role of Ang II in diet-induced obesity by focusing on adipose lipid anabolism and catabolism. Methods Rat model of AT1aR gene knockout were established to investigate the special role of Ang II on adipose lipid metabolism. Wild-type (WT) and AT1aR gene knockout (AT1aR(-/-)) SD rats were fed with normal diet or high-fat diet for 12 weeks. Adipose morphology and adipose lipid synthesis and lipolysis were examined. Results AT1aR deficiency activated lipolysis-related enzymes and increased the levels of NEFAs and glycerol released from adipose tissue in high-fat diet rats, while did not affect triglycerides synthesis. Besides, AT1aR knockout promoted energy expenditure and fatty acids oxidation in adipose tissue. cAMP levels and PKA phosphorylation in the adipose tissue were significantly increased in AT1aR(-/-) rats fed with high-fat. Activated PKA could promote adipose lipolysis and thus improved adipose histomorphology and insulin sensitivity in high-fat diet rats. Conclusions AT1aR deficiency alleviated adipocyte hypertrophy in high-fat diet rats by promoting adipose lipolysis probably via cAMP/PKA pathway, and thereby delayed the onset of obesity and related metabolic diseases.

Automated summary

The study found that AT1aR deficiency promoted adipose lipolysis in high-fat diet rats by activating lipolysis-related enzymes and increasing the levels of NEFAs and glycerol released from adipose tissue, without affecting triglycerides synthesis. Additionally, AT1aR knockout enhanced energy expenditure and fatty acids oxidation in adipose tissue. Increased cAMP levels and PKA phosphorylation in adipose tissue of AT1aR(-/-) rats fed with high-fat diet were observed, which led to improved adipose histomorphology and insulin sensitivity.