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Elife. 2015 Oct 17;4. pii: e08428. doi: 10.7554/eLife.08428.

ANGPTL4 mediates shuttling of lipid fuel to brown adipose tissue during sustained cold exposure.

Author information

1
Nutrition, Metabolism and Genomics group, Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
2
Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
3
Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States.
4
Molecular Biology Institute, University of California, Los Angeles, Los Angeles, United States.
5
Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands.
6
Einthoven Laboratory for Experimental Vascular Medicine, Leiden Univeristy Medical Center, Leiden, The Netherlands.
7
Department of Human Movement Sciences, Maastricht University, Maastricht, The Netherlands.
8
Department of Human Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.
9
Department of Medical Biosciences/Physiological Chemistry, Umeå University, Umeå, Sweden.

Abstract

Brown adipose tissue (BAT) activation via cold exposure is increasingly scrutinized as a potential approach to ameliorate cardio-metabolic risk. Transition to cold temperatures requires changes in the partitioning of energy substrates, re-routing fatty acids to BAT to fuel non-shivering thermogenesis. However, the mechanisms behind the redistribution of energy substrates to BAT remain largely unknown. Angiopoietin-like 4 (ANGPTL4), a protein that inhibits lipoprotein lipase (LPL) activity, is highly expressed in BAT. Here, we demonstrate that ANGPTL4 is part of a shuttling mechanism that directs fatty acids derived from circulating triglyceride-rich lipoproteins to BAT during cold. Specifically, we show that cold markedly down-regulates ANGPTL4 in BAT, likely via activation of AMPK, enhancing LPL activity and uptake of plasma triglyceride-derived fatty acids. In contrast, cold up-regulates ANGPTL4 in WAT, abolishing a cold-induced increase in LPL activity. Together, our data indicate that ANGPTL4 is an important regulator of plasma lipid partitioning during sustained cold.

KEYWORDS:

angiopoietin-like 4; brown adipose tissue; energy metabolism; human biology; lipoprotein lipase; medicine; mouse; triglyceride-rich lipoproteins; white adipose tissue

PMID:
26476336
PMCID:
PMC4709329
DOI:
10.7554/eLife.08428
[Indexed for MEDLINE]
Free PMC Article

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