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

Abstract

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.

The autocrine and paracrine roles of adipokines

“…Thus, initial in vitro experiments suggested that angiotensin II promotes preadipocyte differentiation via the AT 2 receptor (Engeli et al, 2000). Subsequently, however, it was shown that the in vivo effects of angiotensin II are mediated primarily via AT 1 and in this case the end result is expansion of adipose tissue, primarily because of adipocyte hypertrophy, and thus metabolic dysfunction (Massiéra et al, 2001, Tomono et al, 2008.…”

Role of renin–angiotensin system in adipose tissue dysfunction

“…ApoEKO mice showed an enlargement of adipocyte size. 17 In their adipose tissue, the expression of adiponectin and PPARg was lower than that of wild-type mice. These changes in ApoEKO mice were recovered by the deletion of AT 1 a receptor (AT 1 a/ApoE double KO mice).…”

“…Treatment of mice with ARB decreased the plasma level of cholesterol and free fatty acids, 14,17 which is closely related with metabolic syndrome and insulin resistance.…”

“…4 The modulation of insulin signaling and the regulation of oxidative stress are involved in the metabolic action of angiotensin II in adipose tissue. 4,17 These effects of angiotensin II are observed in short-term (or acute) regulation of metabolism. However, the regulation of the total adipose tissue mass depends not only on acute metabolic changes but also on various other factors.…”

“…22 In our earllier report, we showed that the deficiency of AT 1 a receptor, a major subclass of AT 1 receptor, increased the adipocyte differentiation and the number of small-sized adipocytes in atherosclerotic model mice. 17 The role of another subtype of AT 1 receptor, AT 1 b receptor, is totally unknown. Apolipoprotein E-deficient (ApoE-knockout (KO)) mice are widely used as an animal model of atherosclerosis.…”