title: Chronic alcohol consumption has a biphasic effect on hepatic retinoid loss.
abstract: The alcohol-induced depletion of hepatic retinoid stores correlates with the progression of liver injury; however, the mechanisms underlying alcohol's effects have not been fully elucidated. Our goal was to gain a mechanistic understanding of alcohol-induced hepatic retinoid depletion. Wild-type and mutant mice were continuously fed alcohol through Lieber-DeCarli liquid diets, with matched control animals pair fed an isocaloric alcohol-free diet to ensure equal nutrient and calorie intake between groups. A systematic analysis of tissue retinol and retinyl ester levels was performed with HPLC, complemented by gene and protein expression analyses. Our results delineated 2 phases of alcohol-induced depletion of hepatic retinoid. Initially, ∼15% of hepatic retinoid content was mobilized from the liver, causing extrahepatic tissue retinoid levels to increase. Subsequently, there was a precipitous drop in hepatic retinoid content (>60%), without further retinoid accumulation in the periphery. Follow-up studies in mutant mice revealed roles for RBP, CRBP1, and CD36 in retinoid mobilization and extrahepatic retinoid uptake, as well as a role for CYP2E1 in the catabolism of hepatic retinoid. In summary, alcohol has a biphasic effect on hepatic retinoid stores, characterized by an initial phase of rapid mobilization to extrahepatic tissues followed by extensive catabolism within the liver.
authors.affiliation: Department of Medicine, Columbia University, New York, New York, USA rdc2132@columbia.edu.
authors.forename: Robin D
authors.initials: RD
authors.lastname: Clugston
authors.affiliation: Department of Medicine, Columbia University, New York, New York, USA.
authors.forename: Li-Shin
authors.initials: LS
authors.lastname: Huang
authors.affiliation: Department of Medicine, Columbia University, New York, New York, USA.
authors.forename: William S
authors.initials: WS
authors.lastname: Blaner
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D002908:Chronic Disease; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D012176:Retinoids / Q000235:genetics / Q000378:metabolism*; D054840:Retinol-Binding Proteins, Cellular / Q000235:genetics / Q000378:metabolism
chemical_list: D018955:CD36 Antigens; C581954:CrbpI protein, mouse; D012176:Retinoids; D054840:Retinol-Binding Proteins, Cellular
keywords: ethanol; liver; retinoid catabolism; retinoid mobilization; vitamin A