Brown adipose tissue activity controls triglyceride clearance.
Brown adipose tissue (BAT) burns fatty acids for heat production to defend the body against cold and has recently been shown to be present in humans. Triglyceride-rich lipoproteins (TRLs) transport lipids in the bloodstream, where the fatty acid moieties are liberated by the action of lipoprotein lipase (LPL). Peripheral organs such as muscle and adipose tissue take up the fatty acids, whereas the remaining cholesterol-rich remnant particles are cleared by the liver. Elevated plasma triglyceride concentrations and prolonged circulation of cholesterol-rich remnants, especially in diabetic dyslipidemia, are risk factors for cardiovascular disease. 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.
Institute of Biochemistry and Molecular Biology II: Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. abartelt@uke.uni-hamburg.de
Alexander
A
Bartelt
Oliver T
OT
Bruns
Rudolph
R
Reimer
Heinz
H
Hohenberg
Harald
H
Ittrich
Kersten
K
Peldschus
Michael G
MG
Kaul
Ulrich I
UI
Tromsdorf
Horst
H
Weller
Christian
C
Waurisch
Alexander
A
Eychmüller
Philip L S M
PL
Gordts
Franz
F
Rinninger
Karoline
K
Bruegelmann
Barbara
B
Freund
Peter
P
Nielsen
Martin
M
Merkel
Joerg
J
Heeren
D002001:Adipose Tissue, Brown / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D001833:Body Temperature Regulation / Q000502:physiology; D018955:CD36 Antigens / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism / Q000502:physiology; D003080:Cold Temperature; D006801:Humans; D006949:Hyperlipidemias / Q000378:metabolism / Q000503:physiopathology; D007333:Insulin Resistance / Q000502:physiology; D008071:Lipoprotein Lipase / Q000378:metabolism; D008074:Lipoproteins / Q000378:metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology; D014280:Triglycerides / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism / Q000502:physiology
D018955:CD36 Antigens; D008074:Lipoproteins; D014280:Triglycerides; D042461:Vascular Endothelial Growth Factor A; D002784:Cholesterol; D008071:Lipoprotein Lipase
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