Kikai Masakazu, Yamada Hiroyuki, Wakana Noriyuki, Terada Kensuke, Yamamoto Keita, Wada Naotoshi, Motoyama Shinichiro, Saburi Makoto, Sugimoto Takeshi, Irie Daisuke, Kato Taku, Kawahito Hiroyuki, Ogata Takehiro, Matoba Satoaki
Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Biochem Biophys Res Commun. 2018 Mar 18;497(4):1097-1103. doi: 10.1016/j.bbrc.2018.02.185. Epub 2018 Feb 26.
Brown adipose tissue (BAT) has been found 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. Interscapular BAT was dissected from 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 32% compared with the sham control mice. Lipid profiles, except for serum triglyceride level, showed no difference between the 2 groups. BAT-transplanted mice showed higher concentrations of serum noradrenalin, fibroblast growth factor 21 (FGF-21), and adiponectin. Treatment with the β3-adrenergic receptor (AR) blocker completely abrogated the atheroprotective effects of BAT transplantation, with serum concentrations of FGF-21 and adiponectin being equivalent between the 2 groups. Homologous transplantation of BAT from apoE mice also showed a significant decrease in atherosclerotic lesion area by 28% without affecting lipid profiles, while epidydimal white adipose tissue transplantation did not affect atherosclerosis. Serum and endogenous BAT concentrations of FGF-21 were significantly higher in BAT-transplanted mice than sham control mice. Concomitantly, serum adiponectin levels were elevated in BAT-transplanted mice and showed a significant inverse correlation with atherosclerotic lesion area. Our findings show for the first time that atheroprotective effect of BAT transplantation is BAT-specific and independent of lipid-lowering effect, accompanied by AR-mediated activation of the FGF-21-adiponectin axis.
棕色脂肪组织（BAT）已被发现是一种维持代谢稳态的内分泌器官；然而，其对动脉粥样硬化的影响仍不明确。在此，我们研究了实验性BAT移植对动脉粥样硬化的影响。从野生型小鼠肩胛间分离出BAT，并将其移植到12周龄载脂蛋白E（apoE）小鼠的体腔内。高胆固醇饮食3个月后对整个主动脉进行油红O染色显示，与假手术对照小鼠相比，BAT移植小鼠的动脉粥样硬化病变面积显著减少了32%。除血清甘油三酯水平外，两组的血脂谱无差异。BAT移植小鼠的血清去甲肾上腺素、成纤维细胞生长因子21（FGF-21）和脂联素浓度较高。用β3-肾上腺素能受体（AR）阻滞剂治疗完全消除了BAT移植的抗动脉粥样硬化作用，两组间FGF-21和脂联素的血清浓度相当。来自apoE小鼠的BAT同源移植也显示动脉粥样硬化病变面积显著减少了28%，且不影响血脂谱，而附睾白色脂肪组织移植对动脉粥样硬化无影响。BAT移植小鼠的血清和内源性BAT中FGF-21的浓度显著高于假手术对照小鼠。同时，BAT移植小鼠的血清脂联素水平升高，且与动脉粥样硬化病变面积呈显著负相关。我们的研究结果首次表明，BAT移植的抗动脉粥样硬化作用具有BAT特异性且独立于降脂作用，伴有AR介导的FGF-21-脂联素轴的激活。
