Altered hepatic retinyl ester concentration and acyl composition in response to alcohol consumption

Abstract

Retinoids (vitamin A and its metabolites) are essential micronutrients that regulate many cellular processes. Greater than 70% of the body’s retinoid reserves are stored in the liver as retinyl ester (RE). Chronic alcohol consumption induces depletion of hepatic retinoid stores, and the extent of this has been correlated with advancing stages of alcoholic liver disease. The goal of this study was to analyze the mechanisms responsible for depletion of hepatic RE stores by alcohol consumption. A change in the fatty-acyl composition of RE in alcohol-fed mice was observed within two weeks after the start of alcohol consumption. Specifically, alcohol-feeding was associated with a significant decline in hepatic retinyl palmitate levels; however, total RE levels were maintained by a compensatory increase in levels of usually minorRE species, particularly retinyl oleate. Our data suggests that alcohol feeding initially stimulates a futile cycle of RE hydrolysis and synthesis, and that the change in RE acyl composition is associated with a change in the acyl composition of hepatic phosphatidylcholine. The alcohol-induced change in RE acyl composition was specific to the liver, and was not seen in lung or white adipose tissue. This shift in hepatic RE fatty acyl composition is a sensitive indicator of alcohol consumption and may be an early biomarker for events associated with the development of alcoholic liver disease.

Inhibition of Retinoic Acid Biosynthesis by the Bisdichloroacetyldiamine WIN 18,446 Markedly Suppresses Spermatogenesis and Alters Retinoid Metabolism in Mice

“…Although the liver is the major storage organ for vitamin A, the lung contains high levels of retinyl esters in mice (32,33) as our data support. However, WIN 18,446 treatment nearly depleted retinyl esters from the lung but not from the liver (Fig.…”

All-Trans-Retinoic Acid Enhances Mitochondrial Function in Models of Human Liver

“…Hepatic vitamin A stores are depleted in alcoholic liver disease, and vitamin A deficiency is believed to play a role in the development and progression of the disease (Bell et al, 1989;Ward and Peters, 1992;Lee and Jeong, 2012;Clugston et al, 2013). Current data also strongly suggest that altered vitamin A homeostasis and retinoid metabolism is present in nonalcoholic fatty liver disease (NAFLD) and in subsequent steatosis.…”

Diet-dependent retinoid effects on liver gene expression include stellate and inflammation markers and parallel effects of the nuclear repressor Shp

“…The GVAD-LF12 combination also removed all detectable retinol and RE from the liver, thus paralleling the greater retinol depletion from serum (Figure 3B and C). Remarkably, the LF12-LF12 protocol increased the capacity for liver RE by more than two-fold compared to the normal documented range (1000-2000nmol/g) [33-35] and by nearly ten-fold compared to the BD-HFD values (Figure 2B). …”