Abstract
Eukaryotic cells store neutral lipids in cytoplasmic lipid droplets (LDs) enclosed in a monolayer of phospholipids and associated proteins [LD proteins (LDPs)]. Growing evidence has demonstrated that LDPs play important roles in the pathogenesis of liver diseases. However, the composition of liver LDPs and the role of their alterations in hepatosteatosis are not well-understood. In this study, we performed liver proteome and LD sub-proteome profiling to identify enriched proteins in LDs as LDPs, and quantified their changes in a high-fat diet (HFD)-induced fatty liver model. Among 5,000 quantified liver proteins, 101 were enriched by greater than 10-fold in the LD sub-proteome and were classified as LDPs. Differential profiling of LDPs in HFD-induced fatty liver provided a list of candidate LDPs for functional investigation. We tested the function of an upregulated LDP, S100a10, in vivo with adenovirus-mediated gene silencing and found, unexpectedly, that knockdown of S100a10 accelerated progression of HFD-induced liver steatosis. The S100A10 interactome revealed a connection between S100A10 and lipid transporting proteins, suggesting that S100A10 regulates the development and formation of LDs by transporting and trafficking. This study identified LD-enriched sub-proteome in homeostatic as well as HFD-induced fatty livers, providing a rich resource for the LDP research field.
Highlights
Eukaryotic cells store neutral lipids in cytoplasmic lipid droplets (LDs) enclosed in a monolayer of phospholipids and associated proteins [LD proteins (LDPs)]
The most comprehensive list of LDPs was reported by Khan et al [12], which includes 1,520 LDPs in mouse livers following high-fat feeding using isobaric tags for relative and absolute quantification (iTRAQ)
1,070 and 1,481 LDPs were identified in the C2C12 myoblasts [29] and Drosophila S2 cells [28], respectively
Summary
Eukaryotic cells store neutral lipids in cytoplasmic lipid droplets (LDs) enclosed in a monolayer of phospholipids and associated proteins [LD proteins (LDPs)]. We performed liver proteome and LD sub-proteome profiling to identify enriched proteins in LDs as LDPs, and quantified their changes in a high-fat diet (HFD)-induced fatty liver model. Among 5,000 quantified liver proteins, 101 were enriched by greater than 10-fold in the LD sub-proteome and were classified as LDPs. Differential profiling of LDPs in HFD-induced fatty liver provided a list of candidate LDPs for functional investigation. This study identified LD-enriched sub-proteome in homeostatic as well as HFD-induced fatty livers, providing a rich resource for the LDP research field.—Liu, M., R. Differential proteomics profiling identifies LDPs and biological functions in high-fat diet-induced fatty livers.
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