Abstract 16090: Brown Adipose Tissue Transplantation Inhibits Atherosclerosis Development in Recipient Apoe Deficient Mice Without Affecting Glucose Homeostasis
BACKGROUND: Brown adipose tissue (BAT), a key nonshivering thermogenic tissue, has been recently identified as an endocrine organ to regulate glucose homeostasis as well as white adipose tissue. Experimental BAT transplantation has been shown to improve glucose tolerance and insulin sensitivity; however, the beneficial effect of BAT transplantation on atherogenesis remains undefined.
METHOD AND RESULT: Interscapular BAT was removed from 12-week-old C57BL/6 mice and transplanted into the visceral cavity in 12-week-old recipient apoE-/- mice fed a high-cholesterol diet until 24 weeks of age. BAT transplanted mice showed a modest, but significant, decrease in body weight and increase in mean blood pressure as compared with those in sham control mice (4.7%, 12%, respectively, P<0.05). Lipid profile and food intake did not differ between the 2 groups of mice. Intraperitonial glucose tolerance test and insulin tolerance test performed at 24 weeks of age showed that BAT transplantation did not affect both glucose tolerance and insulin sensitivity. However, oil-red-O staining of entire aorta showed a significant decrease in atherosclerotic lesion area by 17 % compared with those in sham control mice (P<0.05). Histomorphological analysis of translated 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, PGC-1α, and PRDM16 were markedly decreased as compared with those in endogenous BAT. In contrast, mRNA and protein levels of insulin growth factor (IGF-1) in transplanted BAT graft were markedly elevated by 22-fold and 7-fold, respectively (P<0.05), whereas IGF-1 mRNA expression level in liver was equivalent between the 2 groups, suggesting that anti-inflammatory effect of IGF-1 secreted by transplanted BAT graft contributes, at least in part, to the inhibited atherosclerosis development in BAT transplanted mice.
CONCLUSION: Our findings demonstrated for the first time that BAT transplantation reduces atherosclerosis development without affecting glucose homeostasis and phenotypic modulation of BAT graft could be a potential therapeutic strategy for preventing atherosclerotic diseases.
Author Disclosures: M. Kikai: None. N. Wakana: None. D. Irie: None. K. Yamamoto: None. K. Terada: None. H. Yamada: None.
- © 2014 by American Heart Association, Inc.