Interleukin-17A exacerbates high-fat diet-induced hepatic steatosis by inhibiting fatty acid β-oxidation.

UNLABELLED

There is a growing body of evidence that the interleukin-17A (IL-17A) signaling pathway contributes to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). However, the mechanism by which IL-17A signaling induces hepatocyte injury is unclear. The aim of the present study was to investigate the significance of the IL-17A axis in NAFLD and to explore the role of IL-17A in high-fat diet (HFD)-induced NAFLD in C57BL/6 mice and oleic acid (OA)-induced lipid accumulation in hepatocytes. Firstly, Consistent upregulation of IL-17A was observed in the HFD-induced steatosis mice but not the normal chow-fed control mice. Administration of IL-17A impaired liver function, aggravated hepatic lipid accumulation by inhibiting fatty acid oxidation in the HFD mice. Conversely, inhibition of IL-17A using an anti-IL-17A monoclonal antibody (mAb) significantly attenuated HFD-induced liver injury. Furthermore, IL-17A accelerated hepatic steatosis through activation of the JNK-PPARα pathway in the HFD mice and OA-preloaded hepatocytes.

CONCLUSION

The present study demonstrated that a high fat diet induces IL-17A expression, which exacerbates the progression of NAFLD by inhibiting fatty acid β-oxidation and promoting the accumulation of triglycerides (TG).