AT₂ Receptor Deficiency Attenuates Adipocyte Differentiation and Decreases Adipocyte Number in Atherosclerotic Mice

Abstract

Background

Previous reports indicated that blockade of AT₁ receptor stimulation attenuated adipocyte dysfunction. However, the effects of AT₂ receptor stimulation on adipose tissue were not yet clear. In the present study, we examined the adipose tissue dysfunction in atherosclerotic apolipoprotein E knockout (ApoEKO) mice with AT₂ receptor deficiency.

Methods

Male ApoEKO and AT₂ receptor/ApoE knockout (AT₂/ApoEKO) mice at 6 weeks of age were treated with a normal diet or a high-cholesterol diet (HCD: 1.25% cholesterol). Markers for adipocyte differentiation and inflammation in adipose tissue were assayed with real-time reverse-transcription-PCR and western blot.

Results

Compared with ApoEKO mice, AT₂/ApoEKO mice with a normal diet showed only a decrease in expression of adiponectin and CCAAT/enhancer binding protein δ (C/EBPδ) in epididymal adipose tissue without changes in body weight, adipose tissue weight, and adipocyte number even at 6 months of age. After HCD for 4 weeks, the weight of both epididymal and retroperitoneal adipose tissue in AT₂/ApoEKO mice was greater than that in ApoEKO mice without a change in body weight. Plasma concentrations of cholesterol and fatty acids were higher in AT₂/ApoEKO mice than in ApoEKO mice. In adipose tissue of AT₂/ApoEKO mice, the adipocyte number was decreased and the expression of peroxisome proliferator–activated receptor γ (PPARγ), C/EBPα, and aP2 was lower than that in ApoEKO mice, in association with an increase in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity.

Conclusions

These results suggest that AT₂ receptor stimulation in adipose tissue is involved in the improvement of adipocyte differentiation and adipose tissue dysfunction in atherosclerotic model.

© American Journal of Hypertension, Ltd. 2009