NUTRITIONAL DETERMINANTS OF NON-ALCOHOLIC STEATOHEPATITIS IN HEPATIC CARCINOGENESIS
Location: Human Nutrition Research Center on Aging
Title: Apo-10'-lycopenoic acid, a lycopene 1 metabolite, increases sirtuin 1 mRNA and protein levels and decreases hepatic fat accumulation in ob/ob mice
| Chung, Jayong S. - |
| Koo, Kyeongok - |
| Lian, Fuzhi - |
| Hu, Kang Quan - |
| Ernst, Hansgeorg - |
| Wang, Xiang-Dong - |
Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: November 30, 2011
Publication Date: January 18, 2012
Citation: Chung, J., Koo, K., Lian, F., Hu, K., Ernst, H., Wang, X. 2012. Apo-10'-lycopenoic acid, a lycopene 1 metabolite, increases sirtuin 1 mRNA and protein levels and decreases hepatic fat accumulation in ob/ob mice. Journal of Nutrition. 142(3):405-410.
Interpretive Summary: It is known that lycopene is beneficial in protecting against high-fat diet induced fatty liver. In the present study, we demonstrated that a biologically active product of lycopene, called apo-10’-lycopenoic acid treatment effectively improves fatty liver in mice fed with high fat diet. We also show this function of apo-10’-lycopenoic acid was associated with the induction of anti-aging gene called Sirt1 as well as its activity in the liver tissue of the mice. This data clearly indicates a significant role of the carotenoid products on preventing fatty liver development.
Lycopene has been shown to be beneficial in protecting against high-fat diet-induced fatty liver. The recent demonstration that lycopene can be converted by carotene 99,10’-oxygenase into a biologically active metabolite, ALA, led us to propose that the function of lycopene can be mediated by ALA. In the present study, male ob/ob mice were fed a liquid high-fat diet
(60% energy from fat) with ALA supplementation (ALA group, 240 mg × kg body weight21 × d21) or without ALA supplementation as the control (C group) for 16 wk. Steatosis, SIRT1 expression and activity, genes involved in lipid metabolism, and ALA concentrations in the livers of mice were examined. The results showed that ALA supplementation resulted in a significant accumulation of ALA in the liver and markedly decreased the steatosis in the ALA group without altering body and liver weights compared to the C group. The mRNA and protein levels of hepatic SIRT1 were higher in the ALA group compared to the C group. SIRT1 activity also was higher in the ALA group, as indicated by the lower levels of acetylated forkhead box class O1 protein levels. In addition, the mRNA level of acetyl CoA carboxylase 1 was significantly lower in the ALA group than in the C group. Because SIRT1 plays a key role in lipid homeostasis, the present study suggests that the lycopene metabolite, ALA, protects against the development of steatosis in ob/ob mice by upregulating SIRT1 gene expression and activity.