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

• Main Authors: Salmaan Ahmed Khan, Edith E. Wollaston-Hayden, Todd W. Markowski, LeeAnn Higgins, Douglas G. Mashek
• Format: Article
• Language: English
• Published: Elsevier 2015-12-01
• Series: Journal of Lipid Research
• Subjects: β-oxidation; liver; nutrition; obesity; proteomics
• Online Access: http://www.sciencedirect.com/science/article/pii/S0022227520309469

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.