Deletion of the angiotensin type 2 receptor in mice protected against high-fat diet-induced obesity and glucose intolerance, and increased lipid oxidation compared to wild-type mice.
Does deletion of the Angiotensin Type 2 Receptor protect against diet-induced obesity and insulin resistance in mice?
Deletion of the AT2R protects mice from diet-induced obesity and insulin resistance, suggesting AT2R signaling contributes to the deleterious effects of a high-fat diet.
The renin-angiotensin system with its active metabolite angiotensin (Ang) II has been related not only to hypertension but also to obesity and insulin resistance. Recent evidence obtained in vitro suggests that the type 2 Ang II receptor (AT2R) mediates the trophic action of Ang II on adipocyte differentiation and lipogenesis. We used AT2R(y/-) mice to delineate a potential role of AT2R in adipose tissue development and metabolism. AT2R(y/-) mice had a normal adiposity but displayed a striking adipose tissue phenotype characterized by small adipocytes and an increase in cell number. In muscle, the expression of several genes involved in lipid metabolism, including fatty acid translocase, uncoupling protein-3, peroxisome proliferator-activated receptors (alpha, delta), and carnitine palmitoyl transferase-1, was increased in AT2R-deficient mice. In response to high-fat feeding, these mice were protected against obesity and obesity-related glucose intolerance, as assessed by glucose tolerance tests. Moreover, lipid oxidation assessed by indirect calorimetry was higher in AT2R-deficient mice than in wild-type mice, irrespective of the diet. This suggests that AT2R-dependent signaling exerts a direct or indirect negative control on lipid utilization in muscles. These data support the idea that AT2R-dependent Ang II signaling increases adipose cell mass and glucose intolerance and thus could participate to the deleterious effects of a high-fat diet.
Yvan‐Charvet et al. (Fri,) conducted a other in Obesity and insulin resistance. AT2R deletion vs. Wild-type mice was evaluated on Adipose tissue phenotype, obesity, and glucose intolerance in response to high-fat feeding. Deletion of the angiotensin type 2 receptor in mice protected against high-fat diet-induced obesity and glucose intolerance, and increased lipid oxidation compared to wild-type mice.