Resveratrol protects muscle cells against palmitate-induced cellular senescence and insulin resistance through ameliorating autophagic flux

Skeletal muscle, a highly metabolic tissue, is particularly vulnerable to increased levels ofsaturated free fatty acids (FFAs). The role of autophagy in saturated FFAs-induced cellularsenescence and insulin resistance in skeletal muscle remains unclear. Therefore, thepresent study was aimed to explore autophagic flux in cellular senescence and insulinresistance induced by palmitate in muscle cells, and whether resveratrol limited theseresponses. Our results showed that palmitate induced cellular senescence in bothmyoblasts and myotubes. In addition, palmitate delayed differentiation in myoblasts andinhibited expression of insulin-stimulated p-AKTSer473 in myotubes. The accumulationsof autophagosome assessed by tandem fluorescent-tagged LC3 demonstrated that autophagicflux was impaired in both palmitate-treated myoblasts and myotubes. Resveratrolprotected muscle cells from palmitate-induced cellular senescence, apoptosis duringdifferentiation, and insulin resistance via ameliorating autophagic flux. The direct influenceof autophagic flux on development of cellular senescence and insulin resistance wasconfirmed by blockage of autophagic flux with chloroquine. In conclusion, impairment ofautophagic flux is crucial for palmitate-induced cellular senescence and insulin resistancein muscle cells. Restoring autophagic flux by resveratrol could be a promising approach toprevent cellular senescence and ameliorate insulin resistance in muscle.