Journal
ONCOTARGET
Volume 7, Issue 17, Pages 23019-23032Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.8552
Keywords
antioxidants; lipid metabolism; myoblasts; oxidative stress; inflammation; Gerotarget
Categories
Funding
- MIUR-PRIN [20125S38FA_002]
- Ministero della Salute [GR-2011-02348047]
- Italian Association for Cancer Research (AIRC) [IG 15403]
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During aging skeletal muscle shows an accumulation of oxidative damage as well as intramyocellular lipid droplets (IMLDs). However, although the impact of these modifications on muscle tissue physiology is well established, the direct effectors critical for their occurrence are poorly understood. Here we show that during aging the main lipase of triacylglycerols, ATGL, significantly declines in gastrocnemius and its downregulation in C2C12 myoblast leads to the accumulation of lipid droplets. Indeed, we observed an increase of oxidative damage to proteins in terms of carbonylation, S-nitrosylation and ubiquitination that is dependent on a defective antioxidant cell response mediated by ATGL-PPAR alpha-PGC-1 alpha. Overall our findings describe a pivotal role for ATGL in the antioxidant/anti-inflammatory response of muscle cells highlighting this lipase as a therapeutic target for fighting the progressive decline in skeletal muscle mass and strength.
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