Blockade of AT1 Receptor Improves Adipocyte Differentiation in Atherosclerotic and Diabetic Models.

BACKGROUND The roles of the angiotensin (Ang) II type 1 (AT₁) receptor in the changes in white adipose tissue were explored in an animal model of atherosclerosis using apolipoprotein E-deficient (ApoEKO) mice. METHODS Apolipoprotein E-deficient (ApoEKO) mice and KK-A^y mice were used. Expression of markers for adipocyte differentiation and inflammation was determined by real-time reverse-transcription polymerase chain reaction. RESULTS Adipose tissue weight and adipocyte size in epididymal white adipose tissue were increased in ApoEKO mice and KK-A^y mice. In the adipose tissue of these models, expression of adiponectin and peroxisome proliferator-activated receptor-γ (PPARγ), which induce adipocyte differentiation, and expression of transcription factors of adipocyte differentiation, such as CCAAT-enhancer-binding protein-α (C/EBPα) and aP2, were decreased. Expression of inflammatory markers and nicotinamide adenine dinucleotide phosphate oxidase subunits was also increased. Deletion of AT₁a receptor in ApoEKO mice and administration of an AT₁ receptor blocker, valsartan, to KK-A^y mice reduced epididymal adipose tissue weight and adipocyte size significantly. Blockade of the AT₁ receptor also reduced the expression of inflammatory chemokines and oxidative stress markers. Moreover, AT₁a receptor deletion in ApoEKO mice and AT₁ receptor blockade in KK-A^y mice prevented the decrease in expression of adiponectin, PPARγ, C/EBPα, and aP2. Valsartan also increased glucose uptake induced by insulin in adipose tissue of KK-A^y mice. CONCLUSIONS These results suggest that enlargement and weakened differentiation of adipocytes are observed in atherosclerosis and diabetes, and that AT₁ receptor blockade prevented adipocyte enlargement and promoted adipocyte differentiation in these models. [ABSTRACT FROM AUTHOR]