ATGL-mediated triglyceride turnover and the regulation of mitochondrial capacity in skeletal muscle

Meex, Ruth C., Hoy, Andrew J., Mason, Rachael M., Martin, Sheree D., McGee, Sean L., Bruce, Clinton R. and Watt, Matthew J. 2015, ATGL-mediated triglyceride turnover and the regulation of mitochondrial capacity in skeletal muscle, AJP - Endocrinology and metabolism, vol. 308, pp. E960-E970, doi: 10.1152/ajpendo.00598.2014.

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Title ATGL-mediated triglyceride turnover and the regulation of mitochondrial capacity in skeletal muscle
Author(s) Meex, Ruth C.
Hoy, Andrew J.
Mason, Rachael M.
Martin, Sheree D.
McGee, Sean L.ORCID iD for McGee, Sean L.
Bruce, Clinton R.ORCID iD for Bruce, Clinton R.
Watt, Matthew J.
Journal name AJP - Endocrinology and metabolism
Volume number 308
Start page E960
End page E970
Total pages 11
Publisher American Physiological Society
Place of publication Bethesda, MD
Publication date 2015-06-01
ISSN 1522-1555
Keyword(s) adipose triglyceride lipase
fatty acid metabolism
Summary Emerging evidence indicates that skeletal muscle lipid droplets are an important control point for intracellular lipid homeostasis and that regulating fatty acid fluxes from lipid droplets might influence mitochondrial capacity. We used pharmacological blockers of the major triglyceride lipases, adipose triglyceride lipase (ATGL) and hormone-sensitive lipase, to show that a large proportion of the fatty acids that are transported into myotubes are trafficked through the intramyocellular triglyceride pool. We next tested whether increasing lipolysis from intramyocellular lipid droplets could activate transcriptional responses to enhance mitochondrial and fatty acid oxidative capacity. ATGL was overexpressed by adenoviral and adenoassociated viral infection in C2C12 myotubes and the tibialis anterior muscle of C57Bl/6 mice, respectively. ATGL overexpression in C2C12 myotubes increased lipolysis, which was associated with increased peroxisome proliferator-activated receptor (PPAR)-∂ activity, transcriptional upregulation of some PPAR∂ target genes, and enhanced mitochondrial capacity. The transcriptional responses were specific to ATGL actions and not a generalized increase in fatty acid flux in the myotubes. Marked ATGL overexpression (20-fold) induced modest molecular changes in the skeletal muscle of mice, but these effects were not sufficient to alter fatty acid oxidation. Together, these data demonstrate the importance of lipid droplets for myocellular fatty acid trafficking and the capacity to modulate mitochondrial capacity by enhancing lipid droplet lipolysis in vitro; however, this adaptive program is of minor importance when superimposing the normal metabolic stresses encountered in free-moving animals.
Language eng
DOI 10.1152/ajpendo.00598.2014
Field of Research 111603 Systems Physiology
Socio Economic Objective 920104 Diabetes
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2015, American Physiological Society
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Document type: Journal Article
Collections: Faculty of Health
Institute for Physical Activity and Nutrition
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