Lycopene Improves Insulin Sensitivity through Inhibition of STAT3/Srebp-1c-Mediated Lipid Accumulation and Inflammation in Mice fed a High-Fat Diet

In the past few years, metabolic disorders, such as type 2 diabetes and metabolic syndrome, have reached global prevalence. Lycopene is one of the major carotenoids in tomatoes, watermelons, red grapefruits, and guava. In the current study, using high fat diet (HFD)-fed mice, we investigated the effect of Lycopene on insulin resistance. We showed that diet containing Lycopene significantly prevented HFD-induced increase of fasting blood glucose and insulin level, glucose and insulin intolerance, and decrease of hepatic glycogen content. We found that Lycopene notably prevented the increase of IL-1, TNF and CRP levels in mice fed HFD. We showed that Lycopene improved the lipid profiles in HFD-fed mice, as evidenced by decrease of systemic and hepatic TC, TG and LDL, and increase of HDL. Lycopene suppressed the increase of the expression of Srebp-1c, FAS and ACC-1 in mice fed HFD. The administration of Lycopene notably prevented the expression and phosphorylation of STAT3 in livers of mice induced by HFD. The treatment of adenovirus carrying STAT3 significantly suppressed the decrease of Srebp-1c expression induced by Lycopene. Furthermore, enhancement of STAT3 signaling by adenovirus markedly blocked the reduction of fasting blood glucose and insulin level. In conclusion, in the current study, we found that Lycopene prevented STAT3 signaling and inhibited Srebp-1c and downstream gene expression, resulting in inhibition of lipid accumulation, inflammation, insulin resistance and metabolic dysfunction. Overall, the data in the study provide better understanding of the beneficial effects of Lycopene against insulin resistance and metabolic disorder.