Blockade of AT1 receptor improves adipocyte differentiation in atherosclerotic and diabetic models

The roles of the angiotensin (Ang) II type 1 (AT(1)) receptor in the changes in white adipose tissue were explored in an animal model of atherosclerosis using apolipoprotein E-deficient (ApoEKO) mice.

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.

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-gamma (PPARgamma), which induce adipocyte differentiation, and expression of transcription factors of adipocyte differentiation, such as CCAAT-enhancer-binding protein-alpha (C/EBPalpha) and aP2, were decreased. Expression of inflammatory markers and nicotinamide adenine dinucleotide phosphate oxidase subunits was also increased. Deletion of AT(1)a receptor in ApoEKO mice and administration of an AT(1) receptor blocker, valsartan, to KK-A(y) mice reduced epididymal adipose tissue weight and adipocyte size significantly. Blockade of the AT(1) receptor also reduced the expression of inflammatory chemokines and oxidative stress markers. Moreover, AT(1)a receptor deletion in ApoEKO mice and AT(1) receptor blockade in KK-A(y) mice prevented the decrease in expression of adiponectin, PPARgamma, C/EBPalpha, and aP2. Valsartan also increased glucose uptake induced by insulin in adipose tissue of KK-A(y) mice.

These results suggest that enlargement and weakened differentiation of adipocytes are observed in atherosclerosis and diabetes, and that AT(1) receptor blockade prevented adipocyte enlargement and promoted adipocyte differentiation in these models.