DHA Inhibits Protein Degradation More Efficiently than EPA by Regulating the PPARγ/NFκB Pathway in C2C12 Myotubes

This study was conducted to evaluate the mechanism by which n-3 PUFA regulated the protein degradation in C2C12 myotubes. Compared with the BSA control, EPA at concentrations from 400 to 600 mu M decreased total protein degradation (P < 0.01). However, the total protein degradation was decreased when the concentrations of DHA ranged from 300 mu M to 700 mu M (P < 0.01). DHA (400 mu M, 24 h) more efficiently decreased the I kappa B alpha phosphorylation and increased in the I kappa B alpha protein level than 400 mu M EPA (P < 0.01). Compared with BSA, 400 mu M EPA and DHA resulted in a 47% or 68% induction of the NF kappa B DNA binding activity, respectively (P < 0.01). Meanwhile, 400 mu M EPA and DHA resulted in a 1.3-fold and 2.0-fold induction of the PPAR gamma expression, respectively (P < 0.01). In C2C12 myotubes for PPAR gamma knockdown, neither 400 mu M EPA nor DHA affected the levels of p-I kappa B alpha, total I kappa B alpha or NF kappa B DNA binding activity compared with BSA (P > 0.05). Interestingly, EPA and DHA both still decreased the total protein degradation, although PPAR gamma knockdown attenuated the suppressive effects of EPA and DHA on the total protein degradation (P < 0.01). These results revealed that DHA inhibits protein degradation more efficiently than EPA by regulating the PPAR gamma/NF-kappa B pathway in C2C12 myotubes.