Brown fat activation reduces hypercholesterolaemia and protects from atherosclerosis development

被引：344

作者：

Berbee, Jimmy F. P. ^{[1
,2
]}

Boon, Mariette R. ^{[1
,2
]}

Khedoe, P. Padmini S. J. ^{[1
,2
,3
]}

Bartelt, Alexander ^{[4
,5
]}

Schlein, Christian ^{[4
]}

Worthmann, Anna ^{[4
]}

Kooijman, Sander ^{[1
,2
]}

Hoeke, Geerte ^{[1
,2
]}

Mol, Isabel M. ^{[1
,2
]}

John, Clara ^{[4
]}

Jung, Caroline ^{[6
]}

Vazirpanah, Nadia ^{[1
,2
]}

Brouwers, Linda P. J. ^{[1
,2
]}

Gordts, Philip L. S. M. ^{[7
]}

Esko, Jeffrey D. ^{[7
]}

Hiemstra, Pieter S. ^{[3
]}

Havekes, Louis M. ^{[1
,2
,8
,9
]}

Scheja, Ludger ^{[4
]}

Heeren, Joerg ^{[4
]}

Rensen, Patrick C. N. ^{[1
,2
]}

机构：

[1] Leiden Univ, Med Ctr, Dept Med, Div Endocrinol, NL-2333 ZA Leiden, Netherlands

[2] Leiden Univ, Med Ctr, Einthoven Lab Expt Vasc Med, NL-2333 ZA Leiden, Netherlands

[3] Leiden Univ, Med Ctr, Dept Pulm, NL-2333 ZA Leiden, Netherlands

[4] Univ Med Ctr Hamburg Eppendorf, Dept Biochem & Mol Cell Biol, D-20246 Hamburg, Germany

[5] Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA

[6] Univ Med Ctr Hamburg Eppendorf, Diagnost & Intervent Radiol, D-20246 Hamburg, Germany

[7] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA

[8] Leiden Univ, Med Ctr, Dept Cardiol, NL-2333 ZA Leiden, Netherlands

[9] Netherlands Org Appl Sci Res Metab Hlth Res, Gaubius Lab, NL-2333 CK Leiden, Netherlands

来源：

NATURE COMMUNICATIONS | 2015年 / 6卷

关键词：

ADIPOSE-TISSUE; APOLIPOPROTEIN-E; ADULT HUMANS; TRIGLYCERIDE CLEARANCE; PLASMA TRIGLYCERIDES; COLD-EXPOSURE; MICE; THERMOGENESIS; RECEPTOR; MITOCHONDRIA;

D O I：

10.1038/ncomms7356

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 beta 3-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.

引用

页数：11

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