ABSTRACT
Although the liver is the primary site of angiotensinogen production, adipocytes have emerged as a major extrahepatic source of angiotensinogen. Angiotensinogen levels are higher in visceral adipose tissue than subcutaneous adipose tissue. Angiotensinogen gene expression is up-regulated by nutritional and hormonal stimuli, as well as during adipogenesis. Clinical and experimental studies have reported activation of circulating and adipose renin-angiotensin-aldosteronesystem (RAAS) in obesity. Positive correlations were found between plasma or adipose angiotensinogen levels and BMI or waist-to-hip ratio in obese subjects. In addition, adipose angiotensinogen mRNA is increased in rodent models of dietinduced obesity. Th e impact of adipose angiotensinogen was supported by gain/ loss of function animals, as well as in weight reduction studies. Angiotensinogen knockout mice were hypotensive, lean, and resistant to diet-induced obesity. Notably, adipocyte-specifi c over-expression of angiotensinogen in both wild-type and angiotensinogen knockout mice increased plasma angiotensinogen levels, BP, and adipose mass, suggesting that adipose angiotensinogen may be a potential link between obesityand hypertension. Weight loss in obese subjects lowered plasma and adipose angiotensinogen levels and decreased BP. Angiotensin II (Ang II), the product of angiotensinogen, modulates adipocyte functions, such as hypertrophy, diff erentiation, adipokine secretion, and induction of oxidative stress and infl ammation. We demonstrated that chronic Ang II infusion in rats induced whole body insulin resistance. Ang II impaired insulin-induced glucose
*Corresponding author
uptake into skeletal muscle and adipocytes by inhibiting GLUT4 translocation to the membrane, possibly via the induction of oxidative stress. Compatible with these fi ndings, several clinical trials have demonstrated that ACE inhibitors and ARBs improve insulin sensitivity and reduce the risk of the development of type 2 diabetes.
