Lycopene attenuates oxidative stress-induced hepatic dysfunction of insulin signal transduction: involvement of FGF21 and mitochondria

Lycopene (LYC) has been regarded as a nutraceutical that has powerful antioxidant and hepatoprotective bioactivities. In the present study, we aimed to investigate the beneficial effects of LYC on hepatic insulin signal transduction under oxidative stress conditions and the possible involvement of FGF21 and mitochondria pathways. Two-month-old CD-1 mice were treated by intraperitoneal injection of D-galactose (D-gal) 150 mg/kg/day for 8 weeks and received 0.03% LYC (w/w, mixed into diet). The results showed that LYC increased the expression of FGF21, alleviated mitochondrial dysfunction and improved hepatic insulin signal transduction in D-gal-treated mice. Furthermore, knockdown of FGF21 by small interfering RNA notably suppressed mitochondrial function and blunted LYC-stimulated insulin signal transduction in H2O2-treated HepG2 cells. Moreover, suppressed mitochondrial function via oligomycin also inhibited insulin signal transduction, indicating that LYC supplementation ameliorated oxidative stress-induced hepatic dysfunction of insulin signal transduction by up-regulating FGF21 and enhancing mitochondrial function.