Chronic alcohol consumption has a biphasic effect on hepatic retinoid loss. Issue 9 (18th May 2015)

• Record Type: Journal Article
• Authors: Clugston, Robin D.; Huang, Li‐Shin; Blaner, William S.
• Is Part Of: FASEB journal. Volume 29:Issue 9(2015)
• Page Start: 3654
• Page End: 3667
• Publication Date: 2015-05-18
• Subjects: liver -- vitamin A -- ethanol -- retinoid mobilization -- retinoid catabolism; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.14-266296
• Languages: English
• ISSNs: 0892-6638

Abstract

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.—Clugston, R. D., Huang, L.‐S., Blaner, W. S. Chronic alcohol consumption has a biphasic effect on hepatic retinoid loss. FASEB J. 29, 3654‐3667 (2015). www.fasebj.org