Abstract 17029: Periaortic Adipose Tissue-Specific Activation of Renin Angiotensin System Along with the Adipocytes Differentiation Contributes to Atherosclerosis in Apoe-/- Mice
[BACKGROUND] Renin angiotensin system (RAS) in visceral white adipose tissue (WAT) plays a crucial role in lipid metabolism and energy homeostasis; however, the role of perivascular adipose tissue RAS in the atherogenesis remains poorly defined.
[METHOD AND RESULT] Periaortic adipose tissue (PAT) is commonly identified as brown adipose tissue, which exhibits strikingly different phenotypes from WAT. We therefore examined the depot-specific difference in the expression levels of adipocyte differentiation-related genes and RAS components in 12-week-old apoE deficient (apoE-/-) mice fed a high-cholesterol diet for 4 weeks. The mRNA expression levels of SREBP1c, PPARγ, and FABP4 were equivalent between PAT and epididymal WAT; however, angiotensinogen (AGT), ACE, and AT1 mRNA expressions were markedly increased in PAT (P<0.05), but not in WAT. We next examined the effect of AT1 deficiency on PAT-specific RAS activation using apoE-/-/AT1 receptor deficient (Agtr1-/-) mice. Expression levels of differentiation-related genes and RAS components except for AT1 were equivalent between the two groups of mice fed a chow diet; however, high-cholesterol diet-induced expressions of differentiation-related genes and RAS components were completely inhibited in apoE-/-/Agtr1-/- PAT (P<0.01). To further examine the association between PAT adipocyte differentiation and RAS activation, we performed primary culture of preadipocyte in stromal vascular fraction isolated from Agtr1-/- and Agtr1+/+ PAT. FACS analysis did not show any difference in preadipocyte population (CD31-CD45-CD34+Sca-1+) between the two groups. Consistent with the in vivo results, the expression levels of differentiation-related genes (c/EBPα, FABP4, and FSP27) were progressively increased accompanied by the enhanced AGT mRNA expression and secretion into the culture medium in Agtr1+/+ adipocyte, which were completely inhibited in Agtr1-/- adipocyte.
[CONCLUSION] Our findings indicate that PAT-specific activation of RAS accompanied by adipocyte differentiation is likely to be elicited by high-cholesterol diet, suggesting that PAT-specific RAS activation accompanied by adipocyte differentiation could be a novel therapeutic target for the prevention of atherosclerosis.
- © 2012 by American Heart Association, Inc.