Abstract 13907: Transplantation of Brown Adipose Tissue Inhibits Atherosclerosis in Apoe Deficient Mice via Activation of Fgf-21/adiponectin Axis
[Background] Brown adipose tissue (BAT), a key nonshivering thermogenic tissue, has been recently identified as an endocrine organ to regulate metabolic homeostasis. Experimental BAT transplantation has been reported to improve glucose tolerance and insulin sensitivity; however, the beneficial effect of BAT transplantation on atherogenesis remains undefined.
[Method and Result] Interscapular BAT was harvested from 12-week-old mice (C57BL/6) and transplanted into the visceral cavity in 12-week-old recipient apoE-/- mice. After 3 months of high-cholesterol diet, atherosclerosis development was evaluated. BAT transplanted mice showed a modest, but significant, decrease in body weight and increase in mean blood pressure compared with sham control mice (4.7%, 12%, respectively, P<0.05). Food intake and lipid profile except for triglyceride level did not differ between the 2 groups. Oil-red-O staining of entire aorta showed a significant decrease in atherosclerotic lesion area in BAT transplanted mice by 19.7 % compared with sham control mice (P<0.05). Histomorphological analysis of transplanted BAT graft showed a similar appearance as white adipose tissue rather than brown adipose tissue. Consistently, mRNA expression levels of brown adipose tissue-related genes such as UCP-1 and PGC-1α were markedly decreased compared with those in endogenous BAT. Interestingly, transplanted BAT graft showed a significantly increased mRNA expression level of fibroblast growth factor-21 (FGF-21), while its expression level in liver was comparable between the 2 groups. The serum concentration of FGF-21 was also increased in BAT transplanted mice (49%, P<0.05), accompanied by the higher concentration of circulating adiponectin (36%, P<0.05). Serum concentration of adiponectin was negatively correlated with the percentage of plaque area (r=-0.44, P<0.05), suggesting that transplanted BAT graft exerts atheroprotective effect via activation of FGF-21/adiponectin axis.
[Conclusion] Our findings demonstrated for the first time that BAT transplantation reduces atherosclerosis development, and phenotypic modulation of BAT graft could be a potential therapeutic strategy for preventing atherosclerotic diseases.
Author Disclosures: M. Kikai: None. K. Terada: None. K. Yamamoto: None. S. Motoyama: None. N. Wada: None. N. Wakana: None. H. Yamada: None.
- © 2015 by American Heart Association, Inc.