Projects per year
Abstract
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 adeno-associated 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) partial differential activity, transcriptional upregulation of some PPAR partial differential 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.
Original language | English |
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Pages (from-to) | 960 - 970 |
Number of pages | 11 |
Journal | American Journal of Physiology - Endocrinology and Metabolism |
Volume | 308 |
Issue number | 11 |
DOIs | |
Publication status | Published - 2015 |
Projects
- 2 Finished
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Curing fatty muscles: understanding the role of PLIN5 in lipid metabolism and tissue function
Watt, M.
National Health and Medical Research Council (NHMRC) (Australia)
1/01/13 → 31/12/15
Project: Research
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Adipose triglyceride lipase: regulation and implications for the aetiology of insulin resistance
Watt, M.
National Health and Medical Research Council (NHMRC) (Australia)
1/01/08 → 31/12/10
Project: Research