Adipose triglyceride lipase decrement affects skeletal muscle homeostasis during aging through FAs-PPARα-PGC-1α antioxidant response

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-PPARα-PGC-1α. 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.