Differential proteomics profiling identifies LDPs and biological functions in high-fat diet-induced fatty livers.
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.
State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, National Center for Protein Sciences (PHOENIX Center), Beijing 102206, China.
Mingwei
M
Liu
State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200433, China.
Rui
R
Ge
State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, National Center for Protein Sciences (PHOENIX Center), Beijing 102206, China.
Wanlin
W
Liu
State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, National Center for Protein Sciences (PHOENIX Center), Beijing 102206, China.
Qiongming
Q
Liu
State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, National Center for Protein Sciences (PHOENIX Center), Beijing 102206, China.
Xia
X
Xia
State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, National Center for Protein Sciences (PHOENIX Center), Beijing 102206, China.
Mi
M
Lai
State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, National Center for Protein Sciences (PHOENIX Center), Beijing 102206, China.
Lizhu
L
Liang
State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, National Center for Protein Sciences (PHOENIX Center), Beijing 102206, China.
Chen
C
Li
State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, National Center for Protein Sciences (PHOENIX Center), Beijing 102206, China.
Lei
L
Song
State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, National Center for Protein Sciences (PHOENIX Center), Beijing 102206, China.
Bei
B
Zhen
State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, National Center for Protein Sciences (PHOENIX Center), Beijing 102206, China; Alkek Center for Molecular Discovery, Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030. Electronic address: jqin@bcm.edu.
Jun
J
Qin
State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, National Center for Protein Sciences (PHOENIX Center), Beijing 102206, China; State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200433, China. Electronic address: crickding@163.com.
Chen
C
Ding
D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects; D005234:Fatty Liver / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D056945:Hep G2 Cells; D006801:Humans; D066292:Lipid Droplets / Q000378:metabolism* / Q000473:pathology; D050356:Lipid Metabolism / Q000235:genetics; D008099:Liver / Q000378:metabolism*; D051379:Mice; D010743:Phospholipids / Q000235:genetics; D014176:Protein Biosynthesis / Q000235:genetics; D020543:Proteome / Q000235:genetics* / Q000378:metabolism; D040901:Proteomics
D010743:Phospholipids; D020543:Proteome
isobaric tags for relative and absolute quantitation; lipid droplet proteins; liver proteomics