Curcumin ameliorates palmitate-induced inflammation in skeletal muscle cells by regulating JNK/NF-kB pathway and ROS production.

Curcumin, a natural polyphenol compound, has the beneficial effects on several diseases such as metabolic syndrome, cancer, and diabetes. The anti-inflammatory property of curcumin has been demonstrated in different cells; however, its role in prevention of palmitate-induced inflammation in skeletal muscle C2C12 cells is not known. In this study, we examined the effect of curcumin on the inflammatory responses stimulated by palmitate in C2C2 cells. The results showed that palmitate upregulated the mRNA expression and protein release of IL-6 and TNF-α cytokines in C2C12 cells, while pretreatment with curcumin was able to attenuate the effect of palmitate on inflammatory cytokines. The anti-inflammatory effect of curcumin was associated with the repression of phosphorylation of IKKα-IKKß, and JNK. Palmitate also caused an increase in reactive oxygen species (ROS) level that curcumin abrogated it. Collectively, these findings suggest that curcumin may represent a promising therapy for prevention of inflammation in skeletal muscle cells.

Palmitate-induced impairment of autophagy turnover leads to increased apoptosis and inflammation in peripheral blood mononuclear cells.

Previous works have linked high concentrations of palmitate to cellular toxicity by autophagy modulation. However, the ways in which palmitate regulates inflammation and apoptosis in peripheral blood mononuclear cells (PBMCs), has not been well characterized. In the present study, we therefore aimed to investigate the role autophagy in inflammatory responses and apoptotic death of PBMCs treated with palmitate. 0.5mM palmitate increased the level of LC3-II at 6h, peaked at 12h and then decreased at 24h. The protein level of p62 was significantly increased at 6h and 12h, suggesting an impairment of autophagic flux in palmitate-treated PBMCs. Inhibiting autophagy with chloroquine (CQ) and 3-Methyladenine (3-MA) significantly augmented palmitate-induced PBMCs apoptotic death as demonstrated by increased cleaved PARP level and increased the percentage of apoptotic (YO-PRO-1 positive and PI negative) cells. Furthermore, CQ pretreatment exacerbated palmitate-induced TNF-α and IL-6 mRNA expression in PBMCs. Moreover, induction of autophagy by pretreatment of PBMCs with rapamycin resulted in a distinct increase of palmitate-induced apoptosis. The induction of autophagy also led to a further increase in palmitate-induced expression of TNF-α and IL-6. These results indicate that the excess palmitate could impair autophagy, hence contributing to palmitate-induced-inflammation and apoptosis in PBMCs. Therefore, dysregulated autophagy in PBMCs may provide a novel mechanism that connects diet-induced obesity to low grade inflammation in patients with type 2 diabetes.