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Cell Metab. 2017 Nov 7;26(5):753-763.e7. doi: 10.1016/j.cmet.2017.09.004. Epub 2017 Oct 5.

Cold-Induced Thermogenesis Depends on ATGL-Mediated Lipolysis in Cardiac Muscle, but Not Brown Adipose Tissue.

Author information

1
Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria. Electronic address: renate.schreiber@uni-graz.at.
2
Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria.
3
Department of Cardiology, Medical University of Graz, 8036 Graz, Austria.
4
Institute of Cell Biology, Histology, and Embryology, Core Facility of Ultrastructural Analyses, Medical University of Graz, 8010 Graz, Austria; BioTechMed-Graz, 8010 Graz, Austria.
5
Department of Human Biology and Human Movement Sciences, School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Centre, Maastricht, the Netherlands.
6
Division of Endocrinology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.
7
Department of Cardiology, Medical University of Graz, 8036 Graz, Austria; BioTechMed-Graz, 8010 Graz, Austria.
8
Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria; BioTechMed-Graz, 8010 Graz, Austria.
9
Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria; BioTechMed-Graz, 8010 Graz, Austria. Electronic address: rudolf.zechner@uni-graz.at.

Abstract

Fatty acids (FAs) activate and fuel UCP1-mediated non-shivering thermogenesis (NST) in brown adipose tissue (BAT). Release of FAs from intracellular fat stores by adipose triglyceride lipase (ATGL) is considered a key step in NST. Accordingly, the severe cold intolerance of global ATGL knockout (AKO) mice has been attributed to defective BAT lipolysis. Here we show that this conclusion is incorrect. We demonstrate that although the BAT-specific loss of ATGL impairs BAT lipolysis and alters BAT morphology, it does not compromise the β3-adrenergic thermogenic response or cold-induced NST. Instead, NST depends on nutrient supply or lipolysis in white adipose tissue during fasting, suggesting that circulating energy substrates are sufficient to fuel NST. Cold intolerance in AKO mice is not caused by BAT dysfunction as previously suspected but by severe cardiomyopathy. We conclude that functional NST requires adequate substrate supply and cardiac function, but does not depend on ATGL-mediated lipolysis in BAT.

KEYWORDS:

adipose triglyceride lipase; brown adipose tissue; cold; heart; lipolysis; thermogenesis; white adipose tissue

PMID:
28988821
PMCID:
PMC5683855
DOI:
10.1016/j.cmet.2017.09.004
[Indexed for MEDLINE]
Free PMC Article

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