Reduced ATGL-mediated lipolysis attenuates β-adrenergic-induced AMPK signaling, but not the induction of PKA-targeted genes, in adipocytes and adipose tissue

Rebecca E. K. MacPherson, Steven M. Dragos, Sofhia Ramos, Charles Sutton, Scott Frendo-Cumbo, Laura Castellani, Matthew J. Watt, Christopher G. R. Perry, David M. Mutch, David C. Wright

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13 Citations (Scopus)

Abstract

5′-AMP-activated protein kinase (AMPK) is activated as a consequence of lipolysis and has been shown to play a role in regulation of adipose tissue mitochondrial content. Conversely, the inhibition of lipolysis has been reported to potentiate the induction of protein kinase A (PKA)-targeted genes involved in the regulation of oxidative metabolism. The purpose of the current study was to address these apparent discrepancies and to more fully examine the relationship between lipolysis, AMPK, and the β-adrenergic-mediated regulation of gene expression. In 3T3-L1 adipocytes, the adipose tissue triglyceride lipase (ATGL) inhibitor ATGListatin attenuated the Thr172phosphorylation of AMPK by a β3-adrenergic agonist (CL 316,243) independent of changes in PKA signaling. Similarly, CL 316,243-induced increases in the Thr172 phosphorylation of AMPK were reduced in adipose tissue from whole body ATGL-deficient mice. Despite reductions in the activation of AMPK, the induction of PKA-targeted genes was intact or, in some cases, increased. Similarly, markers of mitochondrial content and respiration were increased in adipose tissue from ATGL knockout mice independent of changes in the Thr172 phosphorylation of AMPK. Taken together, our data provide evidence that AMPK is not required for the regulation of adipose tissue oxidative capacity in conditions of reduced fatty acid release.

Original languageEnglish
Pages (from-to)C269-C276
Number of pages8
JournalAmerican Journal of Physiology - Cell Physiology
Volume311
Issue number2
DOIs
Publication statusPublished - 1 Aug 2016

Keywords

  • 5'-AMP-activated protein kinase
  • Adipose tissue triglyceride lipase
  • Lipolysis
  • Mitochondria
  • Mouse
  • White adipose tissue

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