NUTRITIONAL DETERMINANTS OF NON-ALCOHOLIC STEATOHEPATITIS IN HEPATIC CARCINOGENESIS
Location: Human Nutrition Research Center on Aging
Title: Chronic alcohol intake up-regulates hepatic expressions of carotenoid cleavage enzymes and peroxisomal proliferator-activated receptors in rats
| Luvizotto, Renata A. - |
| Nascimento, Andre F. - |
| Veeramachnei, Sudipta - |
| Liu, Chun - |
| Wang, Xiang-Dong - |
Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: March 4, 2010
Publication Date: August 11, 2010
Citation: Luvizotto, R., Nascimento, A., Veeramachnei, S., Liu, C., Wang, X. 2010. Chronic alcohol intake up-regulates hepatic expressions of carotenoid cleavage enzymes and peroxisomal proliferator-activated receptors in rats. Journal of Nutrition. 140(10):1808-1814. PMID 20702748.
Interpretive Summary: It is well known that excessive and chronic alcohol intake leads to a lower hepatic vitamin A status by interfering with vitamin A metabolism. However, it is unclear whether chronic alcohol intake affects expressions of carotenoid cleavage enzymes, which converts provitamin A carotenoids into vitamin A. This is the first study to explore the potential interaction between in vivo expressions of carotenoid cleavage enzymes and alcohol intake in a rat model. We demonstrated that chronic alcohol intake up-regulates, rather than down-regulates, hepatic expressions of carotenoid cleavage enzymes. We also show this process may be due to alcohol-reduced vitamin A status in the liver. This information is valuable for understanding the effects of chronic alcohol intake to human health.
Excessive and chronic alcohol intake leads to a lower hepatic vitamin A status by interfering with vitamin A metabolism.Dietary provitamin A carotenoids can be converted into vitamin A mainly by carotenoid 15,15’-monooxygenase 1 (CMO1) and, to a lesser degree, carotenoid 9910’-monooxygenase 2 (CMO2). CMO1 has been shown to be regulated by several transcription factors, such as the PPAR, retinoid X receptor, and thyroid receptor (TR). The regulation ofCMO2has yet to be identified. The impact of chronic alcohol intake on hepatic expressions of CMO1 and CMO2 and their related transcription factors are unknown. In this study, Fischer 344 rats were pair-fed either a liquid ethanol Lieber-DeCarli diet (n = 10) or a control diet (n = 10) for 11 wk. Hepatic retinoid concentration and expressions of CMO1, CMO2, PPARg, PPARa, and TRb
as well as plasma thyroid hormones levels were analyzed. We observed that administering alcohol decreased hepatic retinoid levels but increased mRNA concentrations of CMO1, CMO2, PPARg, PPARa, and TRb and upregulated protein levels of CMO2, PPARg, and PPARa. There was a positive correlation of PPARg with CMO1(r = 0.89; P,0.0001) and both PPARg and PPARa with CMO2 (r = 0.72, P , 0.001 and r = 0.62, P , 0.01, respectively). Plasma thyroid hormone concentrations did not differ between the control rats and alcohol-fed rats. This study suggests that chronic alcohol intake significantly upregulates hepatic expression of CMO1 and, to a much lesser extent, CMO2. This process may be due to alcohol-induced PPARg expression and lower vitamin A status in the liver.