A common observation in metabolic disorders and aging is the elevation of free fatty acids (FFAs), which can form ectopic fat deposition and result in lipotoxicity. Ectopic fat deposition of skeletal muscle has been recognized as an important component of aging, frailty, and sarcopenia. Previous studies have suggested that lipotoxicity caused by FFAs mainly stemmed from saturated fatty acids and decreased unsaturated/saturated fatty acid ratio in serum are also observed among metabolic disorder patients. However, the different effects of saturated fatty acids and unsaturated fatty acids on skeletal muscle are not fully elucidated. In this study, we verified that palmitate (PA), a saturated fatty acid, could lead to impaired differentiative capacity of C2C12 myoblasts by affecting Pax7, MyoD, and myogenin (MyoG), which are master regulators of lineage specification and the myogenic program. Then, oleate (OA), a monounsaturated fatty acid, were added to culture medium together with PA. Results showed that OA could ameliorate the impairment of differentiative capacity in C2C12 myoblast cells. In addition, we found PI3K/Akt signaling pathway played an important role during the process by RNA sequencing and bioinformatics analysis. The positive effect of OA on myoblast differentiative capacity disappeared if PI3K inhibitor LY294002 was added. In conclusion, our study showed that PA could destroy differentiative capacity of C2C12 myoblasts by affecting the expression of Pax7, MyoD, and MyoG, and OA could improve this impairment through PI3K/Akt signaling pathway.
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