title: Quantitative analysis of the murine lipid droplet-associated proteome during diet-induced hepatic steatosis.
abstract: Hepatic steatosis is characterized by the accumulation of lipid droplets (LDs), which are composed of a neutral lipid core surrounded by a phospholipid monolayer embedded with many proteins. Although the LD-associated proteome has been investigated in multiple tissues and organisms, the dynamic changes in the murine LD-associated proteome in response to obesity and hepatic steatosis have not been studied. We characterized the hepatic LD-associated proteome of C57BL/6J male mouse livers following high-fat feeding using isobaric tagging for relative and absolute quantification. Of the 1,520 proteins identified with a 5% local false discovery rate, we report a total of 48 proteins that were increased and 52 proteins that were decreased on LDs in response to high-fat feeding. Most notably, ribosomal and endoplasmic reticulum proteins were increased and extracellular and cytosolic proteins were decreased in response to high-fat feeding. Additionally, many proteins involved in fatty acid catabolism or xenobiotic metabolism were enriched in the LD fraction following high-fat feeding. In contrast, proteins involved in glucose metabolism and liver X receptor or retinoid X receptor activation were decreased on LDs of high-fat-fed mice. This study provides insights into unique biological functions of hepatic LDs under normal and steatotic conditions.
authors.affiliation: Department of Food Science and Nutrition, University of Minnesota, St. Paul, MN 55108.
authors.forename: Salmaan Ahmed
authors.initials: SA
authors.lastname: Khan
authors.affiliation: Department of Food Science and Nutrition, University of Minnesota, St. Paul, MN 55108.
authors.forename: Edith E
authors.initials: EE
authors.lastname: Wollaston-Hayden
authors.affiliation: Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455.
authors.forename: Todd W
authors.initials: TW
authors.lastname: Markowski
authors.affiliation: Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455.
authors.forename: LeeAnn
authors.initials: L
authors.lastname: Higgins
authors.affiliation: Department of Food Science and Nutrition, University of Minnesota, St. Paul, MN 55108 dmashek@umn.edu.
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Mashek
mesh_terms: D000818:Animals; D005234:Fatty Liver / Q000378:metabolism*; D066292:Lipid Droplets / Q000378:metabolism*; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020543:Proteome / Q000378:metabolism*
chemical_list: D020543:Proteome
keywords: liver; nutrition; obesity; proteomics; β-oxidation