Quantitative analysis of the murine lipid dropletassociated proteome during diet-induced hepatic steatosis

Salmaan Ahmed Khan, Edith E. Wollaston-Hayden, Todd W. Markowski, LeeAnn Higgins, Douglas G. Mashek

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

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 highfat 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.

Original languageEnglish (US)
Pages (from-to)2260-2272
Number of pages13
JournalJournal of lipid research
Volume56
Issue number12
DOIs
StatePublished - Dec 1 2015

Bibliographical note

Publisher Copyright:
© 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

Keywords

  • Liver •
  • Nutrition •
  • Obesity •
  • Proteomics
  • β-oxidation •

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