Alcohol-induced microtubule acetylation leads to the accumulation of large, immobile lipid droplets.

Alcohol-induced microtubule acetylation leads to the accumulation of large, immobile lipid droplets. Am J Physiol Gastrointest Liver Physiol. 2019 Aug 02;: Authors: Groebner JL, Giron-Bravo MT, Rothberg ML, Adhikari R, Tuma DJ, Tuma PL Abstract Although steatosis (fatty liver) is a clinically well-described early stage of alcoholic liver disease, surprisingly little is known about how it promotes hepatotoxicity. We have shown that ethanol consumption leads to microtubule hyperacetylation that can explain ethanol-induced defects in protein trafficking. Because almost all steps of the lipid droplet life cycle are microtubule dependent and because microtubule acetylation promotes adipogenesis, we examined droplet dynamics in ethanol-treated cells. In WIF-B cells treated with ethanol and/or oleic acid (a fatty acid associated with the "Western" diet), we found that ethanol dramatically increased lipid droplet numbers and led to the formation of large, peripherally-located droplets. Enhanced droplet formation required alcohol dehydrogenase-mediated ethanol metabolism and peripheral droplet distributions required intact microtubules. We also determined that ethanol-induced microtubule acetylation led to impaired droplet degradation. Live cell imaging revealed that droplet motility was microtubule dependent and that droplets were virtually stationary in ethanol-treated cells. To determine more directly whether microtubule hyperacetylation c...
Source: Am J Physiol Gastroi... - Category: Gastroenterology Authors: Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research