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Nat Commun. 2015 Mar 10;6:6356. doi: 10.1038/ncomms7356.

Brown fat activation reduces hypercholesterolaemia and protects from atherosclerosis development.

Author information

1
1] Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands [2] Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands.
2
1] Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands [2] Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands [3] Department of Pulmonology, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands.
3
1] Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, Hamburg 20246, Germany [2] Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
4
Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, Hamburg 20246, Germany.
5
Diagnostic and Interventional Radiology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, Hamburg 20246, Germany.
6
Department of Cellular and Molecular Medicine, University of California-San Diego, La Jolla, California 92093, USA.
7
Department of Pulmonology, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands.
8
1] Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands [2] Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands [3] Department of Cardiology, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands [4] Netherlands Organization for Applied Scientific Research-Metabolic Health Research, Gaubius Laboratory, Zernikedreef 9, Leiden 2333 CK, The Netherlands.

Abstract

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.

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PMID:
25754609
PMCID:
PMC4366535
DOI:
10.1038/ncomms7356
[Indexed for MEDLINE]
Free PMC Article

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