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

American Journal of Physiology. Gastrointestinal and Liver Physiology
Jennifer L GroebnerPamela L Tuma

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 could explain impaired droplet moti...Continue Reading

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Citations

Feb 26, 2020·International Journal of Molecular Sciences·Manikandan VeerabaguChristiaan van der Schoot
Jan 8, 2020·Contact·Marcus D Kilwein, M A Welte
Nov 5, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Florian GeltingerMark Rinnerthaler
Feb 3, 2021·The International Journal of Biochemistry & Cell Biology·Ling WangWanlu Cao

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Methods Mentioned

BETA
acetylation
nuclear translocation

Software Mentioned

Metamorph
Adobe Photoshop
ImageJ
MTrackJ
IPLabs

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