Lipid Droplet Membrane Proteome Remodeling Parallels Ethanol-Induced Hepatic Steatosis and its Resolution

Authors

Carol A. Casey, University of Nebraska Medical CenterFollow
Terrence Donohue, University of Nebraska Medical CenterFollow
Jacy L. Kubik, University of Nebraska Medical CenterFollow
Vikas Kumar, University of Nebraska Medical CenterFollow
Michael J. Naldrett, University of Nebraska - Lincoln
Nicholas T. Woods, University of Nebraska Medical CenterFollow
Cole P. Frisbie, University of Nebraska Medical Center
Mark A. McNiven, Mayo Clinic College of Medicine
Paul G. Thomes, University of Nebraska Medical CenterFollow

Document Type

Article

Journal Title

Journal of Lipid Research

Publication Date

2-20-2021

Volume

62

Abstract

Lipid droplets (LDs) are composed of neutral lipids enclosed in a phospholipid monolayer, which harbors membrane-associated proteins that regulate LD functions. Despite the crucial role of LDs in lipid metabolism, remodeling of LD protein composition in disease contexts, such as steatosis, remains poorly understood. We hypothesized that chronic ethanol consumption, subsequent abstinence from ethanol, or fasting differentially affects the LD membrane proteome content and that these changes influence how LDs interact with other intracellular organelles. Here, male Wistar rats were pair-fed liquid control or ethanol diets for 6 weeks, and then, randomly chosen animals from both groups were either refed a control diet for 7 days or fasted for 48 h before euthanizing. From all groups, LD membrane proteins from purified liver LDs were analyzed immunochemically and by MS proteomics. Liver LD numbers and sizes were greater in ethanol-fed rats than in pair-fed control, 7-day refed, or fasted rats. Compared with control rats, ethanol feeding markedly altered the LD membrane proteome, enriching LD structural perilipins and proteins involved in lipid biosynthesis, while lowering LD lipase levels. Ethanol feeding also lowered LD-associated mitochondrial and lysosomal proteins. In 7-day refed (i.e., ethanol-abstained) or fasted-ethanol-fed rats, we detected distinct remodeling of the LD proteome, as judged by lower levels of lipid biosynthetic proteins, and enhanced LD interaction with mitochondria and lysosomes. Our study reveals evidence of significant remodeling of the LD membrane proteome that regulates ethanol-induced steatosis, its resolution after withdrawal and abstinence, and changes in LD interactions with other intracellular organelles.

DOI Link

10.1016/j.jlr.2021.100049

ISSN

1539-7262

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Casey, Carol A.; Donohue, Terrence; Kubik, Jacy L.; Kumar, Vikas; Naldrett, Michael J.; Woods, Nicholas T.; Frisbie, Cole P.; McNiven, Mark A.; and Thomes, Paul G., "Lipid Droplet Membrane Proteome Remodeling Parallels Ethanol-Induced Hepatic Steatosis and its Resolution" (2021). Journal Articles: Internal Medicine. 21.
https://digitalcommons.unmc.edu/com_internal_articles/21