title: Reduced ATGL-mediated lipolysis attenuates β-adrenergic-induced AMPK signaling, but not the induction of PKA-targeted genes, in adipocytes and adipose tissue.
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 Thr(172) phosphorylation of AMPK by a β3-adrenergic agonist (CL 316,243) independent of changes in PKA signaling. Similarly, CL 316,243-induced increases in the Thr(172) 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 Thr(172) 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.
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada;
authors.forename: Rebecca E K
authors.initials: RE
authors.lastname: MacPherson
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada;
authors.forename: Steven M
authors.initials: SM
authors.lastname: Dragos
authors.affiliation: School of Kinesiology and Health Sciences, York University, Toronto, Ontario, Canada; and.
authors.forename: Sofhia
authors.initials: S
authors.lastname: Ramos
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada;
authors.forename: Charles
authors.initials: C
authors.lastname: Sutton
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada;
authors.forename: Scott
authors.initials: S
authors.lastname: Frendo-Cumbo
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada;
authors.forename: Laura
authors.initials: L
authors.lastname: Castellani
authors.affiliation: Monash Biomedicine Discovery Institute, Metabolic Disease and Obesity Program, and Department of Physiology, Monash University, Clayton, Victoria, Australia.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Watt
authors.affiliation: School of Kinesiology and Health Sciences, York University, Toronto, Ontario, Canada; and.
authors.forename: Christopher G R
authors.initials: CG
authors.lastname: Perry
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada;
authors.forename: David M
authors.initials: DM
authors.lastname: Mutch
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada; dcwright@uoguelph.ca.
authors.forename: David C
authors.initials: DC
authors.lastname: Wright
mesh_terms: D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D018663:Adrenergic Agents / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D008049:Lipase / Q000378:metabolism*; D008066:Lipolysis / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D000217:Acyltransferases
chemical_list: D055372:AMP-Activated Protein Kinases; D018663:Adrenergic Agents; D000318:Adrenergic beta-Agonists; D017868:Cyclic AMP-Dependent Protein Kinases; D005227:Fatty Acids; D008049:Lipase; C494445:PNPLA2 protein, mouse; D000217:Acyltransferases
keywords: 5′-AMP-activated protein kinase; adipose tissue triglyceride lipase; lipolysis; mitochondria; mouse; white adipose tissue