Brown fat activation reduces hypercholesterolaemia and protects from atherosclerosis development.
Brown fat activation reduces hypercholesterolaemia and protects from atherosclerosis development.
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DOI：
10.1038/ncomms7356
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发表时间：
2015-03-10
影响因子：
16.6
通讯作者：
Rensen PC
中科院分区：
文献类型：
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作者：
Berbée JF;Boon MR;Khedoe PP;Bartelt A;Schlein C;Worthmann A;Kooijman S;Hoeke G;Mol IM;John C;Jung C;Vazirpanah N;Brouwers LP;Gordts PL;Esko JD;Hiemstra PS;Havekes LM;Scheja L;Heeren J;Rensen PC
棕色脂肪组织（BAT）燃烧大量脂肪酸，从而降低血浆甘油三酯水平，减少肥胖。然而，BAT在血浆胆固醇代谢和动脉粥样硬化发展中的确切作用尚不清楚。本研究表明β3-肾上腺素能受体刺激的BAT激活可保护APOE*3-Leiden的高脂血症动脉粥样硬化。CETP小鼠是一种成熟的类人脂蛋白代谢模型，与高脂血症Apoe - / -和Ldlr - / -小鼠不同，它表达功能性Apoe和Ldlr。BAT激活会增加能量消耗，降低血浆甘油三酯和胆固醇水平。从机制上讲，我们证明了BAT的激活增强了脂肪酸从富含甘油三酯的脂蛋白中选择性摄取到BAT，随后加速了富含胆固醇的残留物的肝脏清除。由于BAT在Apoe - / -和Ldlr - / -小鼠中的激活不会减轻高胆固醇血症和动脉粥样硬化，因此这些作用依赖于功能性的肝脏Apoe - Ldlr清除途径。我们的结论是，激活BAT是改善高脂血症和预防动脉粥样硬化的有效治疗途径。棕色脂肪组织（BAT）通过燃烧脂质甘油三酯产生热量。在这里，berb<e:1>等人表明，药理学激活BAT可以保护高脂血症小鼠免受动脉粥样硬化的影响，前提是小鼠保持肝脏清除富含胆固醇的脂蛋白残留物的代谢能力。
Brown adipose tissue (BAT) combusts high amounts of fatty acids, thereby lowering plasma triglyceride levels and reducing obesity. However, the precise role of BAT in plasma cholesterol metabolism and atherosclerosis development remains unclear. Here we show that BAT activation by β3-adrenergic receptor stimulation protects from atherosclerosis in hyperlipidemic APOE*3-Leiden.CETP mice, a well-established model for human-like lipoprotein metabolism that unlike hyperlipidemic Apoe−/− and Ldlr−/− mice expresses functional apoE and LDLR. BAT activation increases energy expenditure and decreases plasma triglyceride and cholesterol levels. Mechanistically, we demonstrate that BAT activation enhances the selective uptake of fatty acids from triglyceride-rich lipoproteins into BAT, subsequently accelerating the hepatic clearance of the cholesterol-enriched remnants. These effects depend on a functional hepatic apoE-LDLR clearance pathway as BAT activation in Apoe−/− and Ldlr−/− mice does not attenuate hypercholesterolaemia and atherosclerosis. We conclude that activation of BAT is a powerful therapeutic avenue to ameliorate hyperlipidaemia and protect from atherosclerosis. Brown adipose tissue (BAT) produces heat by burning lipid triglycerides. Here, Berbée et al. show that pharmacological BAT activation protects hyperlipidemic mice from atherosclerosis, provided mice retain the metabolic capacity to clear cholesterol-enriched lipoprotein remnants by the liver.