Caffeic acid phenethyl ester reduces the activation of the nuclear factor κB pathway by high-fat diet-induced obesity in mice.

OBJECTIVE

The aim of this study was to investigate the effect of CAPE on the insulin signaling and inflammatory pathway in the liver of mice with high fat diet induced obesity.

MATERIAL/

METHODS

Swiss mice were fed with standard chow or high-fat diet for 12-week. After the eighth week, animals in the HFD group with serum glucose levels higher than 200 mg/dL were divided into two groups, HFD and HFD receiving 30 mg/kg of CAPE for 4 weeks. After 12 weeks, the blood samples could be collected and liver tissue extracted for hormonal and biochemical measurements, and insulin signaling and inflammatory pathway analyzes.

RESULTS

The high-fat diet group exhibited more weight gain, glucose intolerance, and hepatic steatosis compared with standard diet group. The CAPE treatment showed improvement in glucose sensitivity characterized by an area under glucose curve similar to the control group in an oral glucose tolerance test Furthermore, CAPE treatment promoted amelioration in hepatic steatosis compared with the high-fat diet group. The increase in glucose sensitivity was associated with the improvement in insulin-stimulated phosphorylation of the insulin receptor substrate-2, followed by an increase in Akt phosphorylation. In addition, it was observed that CAPE reduced the induction of the inflammatory pathway, c-jun-N- terminal kinase, the nuclear factor kappa B, and cyclooxygenase-2 expression, respectively.

CONCLUSIONS

Overall, these findings indicate that CAPE exhibited anti-inflammatory activity that partly restores normal metabolism, reduces the molecular changes observed in obesity and insulin resistance, and therefore has a potential as a therapeutic agent in obesity.