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

Publication date: 7 November 2017
Source:Cell Metabolism, Volume 26, Issue 5
Author(s): Renate Schreiber, Clemens Diwoky, Gabriele Schoiswohl, Ursula Feiler, Nuttaporn Wongsiriroj, Mahmoud Abdellatif, Dagmar Kolb, Joris Hoeks, Erin E. Kershaw, Simon Sedej, Patrick Schrauwen, Guenter Haemmerle, Rudolf Zechner
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.

Graphical abstract

Teaser

Schreiber et al. demonstrate that ATGL-mediated lipolysis in brown adipose tissue is not a prerequisite for cold-induced non-shivering thermogenesis in vivo. Instead, ATGL in white adipose tissue and the heart is essential for supplying fatty acids during fasting and for meeting increased demands on the cardiovascular system in the cold, respectively.


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