Thermogenic adipocytes promote HDL turnover and reverse cholesterol transport.
Thermogenic adipocytes promote HDL turnover and reverse cholesterol transport.
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DOI：
10.1038/ncomms15010
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发表时间：
2017-04-19
影响因子：
16.6
通讯作者：
Heeren J
中科院分区：
文献类型：
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作者：
Bartelt A;John C;Schaltenberg N;Berbée JFP;Worthmann A;Cherradi ML;Schlein C;Piepenburg J;Boon MR;Rinninger F;Heine M;Toedter K;Niemeier A;Nilsson SK;Fischer M;Wijers SL;van Marken Lichtenbelt W;Scheja L;Rensen PCN;Heeren J
棕色和米色脂肪细胞燃烧营养物质以产热，并通过它们的代谢活动减少高脂血症小鼠中导致动脉粥样硬化的残余脂蛋白。然而，生热脂肪细胞的激活是否会影响高密度脂蛋白(高密度脂蛋白)的代谢和抗动脉粥样硬化特性尚不清楚。在这里，我们报道了在APOE*3-Leden.CETP小鼠中，通过药物刺激产热与增加高密度脂蛋白水平有关的动脉粥样硬化的减少。冷诱导和药物生热激活都能促进高密度脂蛋白的重塑，这与小鼠和人类高密度脂蛋白的特定脂体变化有关。此外，生热刺激促进高密度脂蛋白-胆固醇的清除，并增加小鼠巨噬细胞到粪便的反向胆固醇运输。从机制上讲，脂肪细胞脂蛋白脂酶引起的血管内脂解和肝脏清道夫受体B-I对高密度脂蛋白的摄取是高密度脂蛋白在肝脏中处置的驱动力。我们的发现证实了这样一种观点，即生热脂肪细胞的高代谢活性通过增加通过高密度脂蛋白的全身胆固醇流量来提供动脉粥样硬化保护特性。在动物模型中，棕色脂肪组织(BAT)的激活可减少动脉粥样硬化的发生。在这里，作者表明BAT激活也增加了胆固醇的反向运输和高密度脂蛋白的周转，这可能有助于BAT激活的抗动脉粥样硬化作用。
Brown and beige adipocytes combust nutrients for thermogenesis and through their metabolic activity decrease pro-atherogenic remnant lipoproteins in hyperlipidemic mice. However, whether the activation of thermogenic adipocytes affects the metabolism and anti-atherogenic properties of high-density lipoproteins (HDL) is unknown. Here, we report a reduction in atherosclerosis in response to pharmacological stimulation of thermogenesis linked to increased HDL levels in APOE*3-Leiden.CETP mice. Both cold-induced and pharmacological thermogenic activation enhances HDL remodelling, which is associated with specific lipidomic changes in mouse and human HDL. Furthermore, thermogenic stimulation promotes HDL-cholesterol clearance and increases macrophage-to-faeces reverse cholesterol transport in mice. Mechanistically, we show that intravascular lipolysis by adipocyte lipoprotein lipase and hepatic uptake of HDL by scavenger receptor B-I are the driving forces of HDL-cholesterol disposal in liver. Our findings corroborate the notion that high metabolic activity of thermogenic adipocytes confers atheroprotective properties via increased systemic cholesterol flux through the HDL compartment. Activation of brown adipose tissue (BAT) reduces the development of atherosclerosis in animal models. Here the authors show that BAT activation also increases reverse cholesterol transport and turnover of high-density lipoprotein, which likely contributes to the anti-atherosclerotic effect of BAT activation.