Irbesartan increased PPARγ activity in vivo in white adipose tissue of atherosclerotic mice and improved adipose tissue dysfunction

The effect of the PPARγ agonistic action of an AT1 receptor blocker, irbesartan, on adipose tissue dysfunction was explored using atherosclerotic model mice. Adult male apolipoprotein E-deficient (ApoEKO) mice at 9 weeks of age were treated with a high-cholesterol diet (HCD) with or without irbesartan at a dose of 50 mg/kg/day for 4 weeks. The weight of epididymal and retroperitoneal adipose tissue was decreased by irbesartan without changing food intake or body weight. Treatment with irbesartan increased the expression of PPARγ in white adipose tissue and the DNA-binding activity of PPARγ in nuclear extract prepared from adipose tissue. The expression of adiponectin, leptin and insulin receptor was also increased by irbesartan. These results suggest that irbesartan induced activation of PPARγ and improved adipose tissue dysfunction including insulin resistance.

Research highlights► Atherosclerotic apolipoprotein E-deficient (ApoEKO) mice were treated with irbesartan. ► Irbesartan decreased white adipose tissue weight without affecting body weight. ► DNA-binding for PPARγ was increased in white adipose tissue in vivo by irbesartan. ► Irbesartan increased adipocyte number in white adipose tissue. ► Irbesatan increased the expression of adiponectin and leptin in white adipose tissue.