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- Title
Transplantation of brown adipose tissue inhibits atherosclerosis in apoE<sup>-l-</sup> mice: contribution of the activated FGF-21-adiponectin axis.
- Authors
Masakazu Kikai; Hiroyuki Yamada; Noriyuki Wakana; Kensuke Terada; Keita Yamamoto; Naotoshi Wada; Shinichiro Motoyama; Makoto Saburi; Takeshi Sugimoto; Daisuke Irie; Taku Kato; Hiroyuki Kawahito; Takehiro Ogata; Satoaki Matoba
- Abstract
Aims Brown adipose tissue (BAT) has been identified as an endocrine organ that maintains metabolic homeostasis; however, the effects on atherosclerosis remain undefined. Here, we investigated the effect of experimental BAT transplantation on atherosclerosis. Methods and results Interscapular BAT was dissected from 12-week-old wild-type mice and transplanted into the visceral cavity of 12-week-old apoE-/- mice. Oil-red O staining of whole aortas after 3 months of a high-cholesterol diet showed a significant decrease in atherosclerotic lesion area in BAT-transplanted mice by 20% compared with the sham control mice. A significant increase in oxygen consumption and energy expenditure, concomitant improvement of glucose tolerance, and lower triglyceride levels were observed in BAT-transplanted mice; however, serum cholesterol levels showed no difference between the two groups. Homologous transplantation of BAT from apoE-/- mice also showed a significant decrease in atherosclerotic lesion area by 28% compared with the sham control apoE-/- mice without affecting lipid levels, while epidydimal white adipose tissue transplantation did not affect atherosclerosis. In the combination of wild-type donor and apoE-/- recipient mice, both mRNA and protein levels of fibroblast growth factor 21 (FGF-21) were increased significantly in endogenous BAT in BAT-transplanted mice (180 and 38%, respectively, P < 0.05), accompanied by a higher concentration of circulating FGF-21 and noradrenaline (47 and 45%, respectively, P < 0.05). Concomitantly, serum adiponectin levels were elevated in BAT-transplanted mice (35%, P < 0.05), and showed an inverse correlation with atherosclerotic lesion area (r = 0.44, P < 0.05). Treatment with the nonselective β3-adrenergic receptor (AR) blocker completely abolished the anti-atherogenic effect of BAT transplantation and reduced concentrations of circulating FGF-21 and adiponectin to levels comparable with that of vehicle-treated BAT-transplanted mice. Conclusions Our findings demonstrate for the first time that anti-atherogenic action of BAT transplantation is BAT-specific and independent of lipid-lowering effect, accompanied by AR-mediated activation of the FGF-21-adiponectin axis.
- Subjects
ATHEROSCLEROSIS; BROWN adipose tissue; ADIPOSE tissue transplantation; FIBROBLAST growth factors; ADIPONECTIN
- Publication
Cardiovascular Research, 2018, Vol 114, Issue 6, pi1
- ISSN
0008-6363
- Publication type
Article
- DOI
10.1093/cvr/cvx212