title: Intracellular pigment epithelium-derived factor contributes to triglyceride degradation.
abstract: Pigment epithelium-derived factor is well known as a secreted glycoprotein with multiple functions, such as anti-angiogenic, neuroprotective and anti-tumor activities. However, its intracellular role remains unknown. The present study was performed to demonstrate the intracellular function of pigment epithelium-derived factor on triglyceride degradation. Hepatic pigment epithelium-derived factor levels increased at the early stage and subsequently decreased after 16 weeks in high-fat-diet-fed mice compared to those in chow-fed mice. Similarly, oleic acid led to long-term downregulation of pigment epithelium-derived factor in HepG2 cells. Endogenous pigment epithelium-derived factor was an intracellular protein with cytoplasmic distribution in hepatocytes by immunostaining. Exogenous FITC-labeled pigment epithelium-derived factor could be absorbed into hepatocytes. Both signal peptide deletion and full-length pigment epithelium-derived factor transfection HeLa cells and hepatocytes promoted triglyceride degradation. Intracellular pigment epithelium-derived factor co-immunoprecipitated with adipose triglyceride lipase and promoted triglyceride degradation in an adipose triglyceride lipase-dependent manner. Additionally, pigment epithelium-derived factor bound to the C-terminal of adipose triglyceride lipase (aa268-504) and adipose triglyceride lipase-G0/G1 switch gene-2 complex simultaneously, which facilitated adipose triglyceride lipase-G0/G1 switch gene-2 translocation onto lipid droplet using bimolecular fluorescence complementation assay. Moreover, knockdown of endogenous pigment epithelium-derived factor in hepatocytes diminished triglyceride degradation. Taken together, these results indicate that hepatic pigment epithelium-derived factor was decreased in obese mice accompanied with hepatic steatosis. Intracellular pigment epithelium-derived factor binds to and facilitates adipose triglyceride lipase translocation onto lipid droplet, which promotes triglyceride degradation. These findings suggest that a decreased level of hepatic pigment epithelium-derived factor may contribute to hepatic steatosis in obesity.
authors.affiliation: Department of Biochemistry, Zhongshan Medical School, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Dai
authors.forename: Ti
authors.initials: T
authors.lastname: Zhou
authors.forename: Cen
authors.initials: C
authors.lastname: Li
authors.forename: Weiwei
authors.initials: W
authors.lastname: Qi
authors.forename: Yuling
authors.initials: Y
authors.lastname: Mao
authors.forename: Juling
authors.initials: J
authors.lastname: Lu
authors.forename: Yachao
authors.initials: Y
authors.lastname: Yao
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.forename: Honghai
authors.initials: H
authors.lastname: Hong
authors.forename: Shuai
authors.initials: S
authors.lastname: Li
authors.forename: Weibin
authors.initials: W
authors.lastname: Cai
authors.forename: Zhonghan
authors.initials: Z
authors.lastname: Yang
authors.forename: Jianxing
authors.initials: J
authors.lastname: Ma
authors.forename: Xia
authors.initials: X
authors.lastname: Yang
authors.forename: Guoquan
authors.initials: G
authors.lastname: Gao
mesh_terms: D000818:Animals; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D015843:Serpins / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism*; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D005136:Eye Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D014280:Triglycerides; D000099174:Pigment Epithelium-Derived Factor
keywords: ATGL; BiFc; CGI-58; FFA; G0/G1 switch gene-2; G0S2; HD; HFD; Hepatocyte; Lipid droplet; PD; PEDF; Triglyceride; adipose triglyceride lipase; bimolecular fluorescence complementation; comparative gene identification-58; free fatty acid; high fat diet; hydrophobic domain; mPEDF; patatin domain; pigment-epithelium derived factor; signal peptide deletion PEDF