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

Abstract

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-1β, TNFα 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.

<p>Lycopene Improves the Metformin Effects on Glycemic Control and Decreases Biomarkers of Glycoxidative Stress in Diabetic Rats</p>

“…The treatment with lycopene for 35 days avoided the progressive increase in the postprandial glycemia, which could be a consequence, at least in part, of the improvements observed in the glucose tolerance. Supporting this hypothesis, studies have found that supplementations with lycopene 34 or with dry tomato peel 35 reduced both the glucose intolerance and the insulin resistance in high-fat diet-fed mice. In addition, a recent review by Zhu et al 36 supports evidence of the lycopene beneficial effects on maintaining the pancreatic function in in vivo models of metabolic dysfunctions.…”

Nutrition, Bioenergetics, and Metabolic Syndrome

“…Based on the potent antioxidant and lipid-lowering properties of lycopene, different studies have assessed it as a beneficial nutrient for the prevention and treatment of MetS. Animal and human-based studies have shown that lycopene reduces blood pressure [ 210 , 211 ], atherosclerotic burden [ 248 ] and improves blood antioxidant capacity [ 246 , 249 ], has an anti-obesity role [ 212 , 213 ], improves insulin sensitivity, reduces hyperglycemia [ 216 , 217 ], and improves the lipid profile [ 214 , 215 ]. Moreover, a retrospective study with 2500 patients with MetS showed that higher serum levels of lycopene are associated with a reduced risk of death [ 250 ].…”

Dietary Momordica Cochinchinensis aril ameliorates metabolic dysfunction, nonalcoholic fatty liver, and gut microbiota in diet-induced obese mice

“…These findings suggest MCA prevented increases in the level of glucose in plasma, and improved insulin sensitivity. Lycopene has been showed to have significant inhibitory effects on HFD-induced insulin resistance by preventing the expression and phosphorylation of STAT3 in a mouse model [36]. In addition, plasma ß-carotene has been shown to have reversed correlation with insulin resistance [37].…”