Brown adipose tissue activity controls triglyceride clearance

内分泌学 内科学 脂肪组织 甘油三酯 褐色脂肪组织 脂蛋白脂酶 生物 高脂血症 脂蛋白 胆固醇 医学 糖尿病
作者
Alexander Bartelt,Oliver T. Bruns†,Rudolph Reimer,Heinz Hohenberg,Harald Ittrich,Kersten Peldschus,Michael G. Kaul,Ulrich I. Tromsdorf,Horst Weller,Christian Waurisch,Alexander Eychmüller,Philip L.S.M. Gordts,Franz Rinninger,Karoline Bruegelmann,Barbara Freund,Peter Brønnum Nielsen,Martin Merkel,Jöerg Heeren
出处
期刊:Nature Medicine [Nature Portfolio]
卷期号:17 (2): 200-205 被引量:1590
标识
DOI:10.1038/nm.2297
摘要

Elevated triglyceride levels often occur in obesity and can contribute to cardiovascular disease. Brown adipose tissue (BAT) is known to burn fat, and now Joerg Heeren and his colleagues show that BAT actively takes up triglycerides in cold conditions, suggesting a possible therapy to lower triglyceride levels in states of obesity. Brown adipose tissue (BAT) burns fatty acids for heat production to defend the body against cold1,2 and has recently been shown to be present in humans3,4,5. Triglyceride-rich lipoproteins (TRLs) transport lipids in the bloodstream, where the fatty acid moieties are liberated by the action of lipoprotein lipase (LPL)6. Peripheral organs such as muscle and adipose tissue take up the fatty acids, whereas the remaining cholesterol-rich remnant particles are cleared by the liver6. Elevated plasma triglyceride concentrations and prolonged circulation of cholesterol-rich remnants, especially in diabetic dyslipidemia, are risk factors for cardiovascular disease7,8,9,10,11. However, the precise biological role of BAT for TRL clearance remains unclear. Here we show that increased BAT activity induced by short-term cold exposure controls TRL metabolism in mice. Cold exposure drastically accelerated plasma clearance of triglycerides as a result of increased uptake into BAT, a process crucially dependent on local LPL activity and transmembrane receptor CD36. In pathophysiological settings, cold exposure corrected hyperlipidemia and improved deleterious effects of insulin resistance. In conclusion, BAT activity controls vascular lipoprotein homeostasis by inducing a metabolic program that boosts TRL turnover and channels lipids into BAT. Activation of BAT might be a therapeutic approach to reduce elevated triglyceride concentrations and combat obesity in humans.
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