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

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*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

156 Citations (Web of Science)

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 beta(3)-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.

Original languageEnglish
Pages (from-to)753-763.e7
Number of pages18
JournalCell Metabolism
Volume26
Issue number5
DOIs
Publication statusPublished - 7 Nov 2017

Keywords

  • HORMONE-SENSITIVE LIPASE
  • TRIGLYCERIDE LIPASE
  • NONSHIVERING THERMOGENESIS
  • INSULIN SENSITIVITY
  • MITOCHONDRIAL-FUNCTION
  • UNCOUPLING PROTEIN-1
  • GLUCOSE-HOMEOSTASIS
  • ENERGY-METABOLISM
  • LIPID-METABOLISM
  • ADULT HUMANS

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