Chronic Alcohol Intake Upregulates Hepatic Expression of Carotenoid Cleavage Enzymes and PPAR in Rats

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 9'10'-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 of CMO2 has 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, PPAR gamma, PPAR alpha, and TR beta 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, PPAR gamma, PPAR alpha, and TR beta and upregulated protein levels of CMO2, PPAR gamma, and PPAR alpha. There was a positive correlation of PPAR gamma with CMO1 (r = 0.89; P < 0.0001) and both PPAR gamma and PPAR alpha 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 PPAR gamma expression and lower vitamin A status in the liver. J. Nutr. 140: 1808-1814, 2010.