Abstract 1652: Deletion of Angiotensin II Type 1 Receptor Enhances Adipocyte Differentiation and Inhibits Atherogenesis in Atherosclerotic Mouse Model
Objective: To explore the roles of angiotensin II type 1 (AT1) receptor stimulation in adipose tissue function in metabolic syndrome, we compared the changes in white adipose tissue using atherosclerotic model of apolipoprotein E-deficient (ApoEKO) with or without AT1 receptor deletion.
Methods and Results: In ApoEKO mice fed with standard chow for 6 months, the adipocyte size was increased and the expression of adiponectin, PPARγ, and a adipocyte differentiation marker, C/EBPδ, determined by real-time RT-PCR in epididymal adipose tissue was decreased, compared with those in wild type (C57BL/6) mice. Decrease in adipocyte size and increase in mRNA for adiponectin, PPARγ, C/EBPδ in epididymal adipose tissue, and smaller atherosclerotic lesion in the aorta were observed in ApoEKO mice with AT1a receptor deletion (AT1a/ApoEKO mice) compared to those in ApoEKO mice. Serum adiponectin concentration was higher in AT1a/ApoEKO mice than ApoEKO mice in spite of smaller adipose tissue size. Systolic blood pressure was lower in AT1a/ApoEKO mice than in ApoEKO mice, but serum concentrations of cholesterol, triglyceride and free fatty acids were not different in both groups. Increase in epididymal adipose tissue weight and adipocyte size was also observed in diabetic KK-Ay mice at 12 weeks of age. An AT1 receptor blocker, valsartan (1 mg/kg/day for 2 weeks, i.p.), significantly inhibited these changes in KK-Ay mice without significant changes in systolic blood pressure. Moreover, valsartan reduced the expression of mRNA for TNF-α and MCP-1 and increased the expression of adiponectin mRNA in epididymal adipose tissue of KK-Ay mice.
Conclusion: These results suggest that disordered functions of adipose tissue with impairment of adipocyte differentiation were observed in atherosclerotic and type 2 diabetic mouse models. AT1 receptor blockade could ameliorates adipose tissue functions observed in atherosclerosis and diabetes, thereby it may have beneficial effects to prevent metabolic syndrome.