title: DGAT1-deficiency affects the cellular distribution of hepatic retinoid and attenuates the progression of CCl4-induced liver fibrosis.
abstract: BACKGROUND
  Diacylglycerol O-acyltransferase 1 (DGAT1) catalyzes the final step of triglyceride synthesis, transferring an acyl group from acyl-CoA to diacylglycerol. DGAT1 also catalyzes the acyl-CoA-dependent formation of retinyl esters in vitro and in mouse intestine and skin. Although DGAT1 is expressed in both hepatocytes and hepatic stellate cells (HSCs), we reported genetic and nutritional studies that established that DGAT1 does not contribute to retinyl ester formation in the liver.
  
  
  METHODS
  We now have explored in more depth the role(s) of DGAT1 in hepatic retinoid metabolism and storage.
  
  
  RESULTS
  Our data show that DGAT1 affects the cellular distribution between hepatocytes and HSCs of stored and newly absorbed dietary retinol. For livers of Dgat1-deficient mice, a greater percentage of stored retinyl ester is present in HSCs at the expense of hepatocytes. This is also true for newly absorbed oral [(3)H]retinol. These differences are associated with significantly increased expression, by 2.8-fold, of cellular retinol-binding protein, type I (RBP1) in freshly isolated HSCs from Dgat1-deficient mice, raising the possibility that RBP1, which contributes to retinol uptake into cells and retinyl ester synthesis, accounts for the differences. We further show that the retinyl ester-containing lipid droplets in HSCs are affected in Dgat1-null mice, being fewer in number but, on average, larger than in wild type (WT) HSCs. Finally, we demonstrate that DGAT1 affects experimentally induced HSC activation in vivo but that this effect is independent of altered retinoic acid availability or effects on gene expression.
  
  
  CONCLUSIONS
  Our studies establish that DGAT1 has a role in hepatic retinoid storage and metabolism, but this does not involve direct actions of DGAT1 in retinyl ester synthesis.
authors.affiliation: Department of Medicine, Columbia University, New York, NY 10032, USA.
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Yuen
authors.affiliation: Department of Medicine, Columbia University, New York, NY 10032, USA.
authors.forename: Seung-Ah
authors.initials: SA
authors.lastname: Lee
authors.affiliation: Department of Medicine, Columbia University, New York, NY 10032, USA.
authors.forename: Hongfeng
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Medicine, Columbia University, New York, NY 10032, USA.
authors.forename: Pierre-Jacques
authors.initials: PJ
authors.lastname: Brun
authors.affiliation: Department of Medicine, Columbia University, New York, NY 10032, USA.
authors.forename: William S
authors.initials: WS
authors.lastname: Blaner
keywords: Hepatic stellate cell (HSC); diacylglycerol acyltransferase 1 (DGAT1); hepatic fibrosis; lipid droplet; retinoic acid; retinyl ester