title: NS5ATP6 modulates intracellular triglyceride content through FGF21 and independently of SIRT1 and SREBP1.
abstract: The prevalence of nonalcoholic fatty liver disease (NAFLD) is rising strikingly in Western countries and China. The molecular biological mechanism of NAFLD remains unclear, with no effective therapies developed so far. Fibroblast growth factor 21 (FGF21) is a recently discovered hormone, with safe lipid lowering effects. FGF21 analogs are being developed for clinical application. Here we demonstrated that a novel gene, NS5ATP6, modulated intracellular triglyceride (TG) content independently of sirtuin1 (SIRT1) and sterol regulatory element binding protein 1 (SREBP1) in HepG2 cells. Interestingly, NS5ATP6 regulated FGF21 expression both at the mRNA and protein levels. The modulatory effects of NS5ATP6 on intracellular TG content depended upon FGF21. Further studies revealed that NS5ATP6 decreased the promoter activity of FGF21. In addition, NS5ATP6 regulated the expression of miR-577, which directly targeted and regulated FGF21. Therefore, miR-577 might be involved in NS5ATP6 regulation of FGF21 at the post-transcriptional level. In conclusion, NS5ATP6 regulates the intracellular TG level via FGF21, and independently of SIRT1 and SREBP1.
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China; Beijing Key Laboratory of Emerging Infectious Diseases, Beijing 100015, China.
authors.forename: Zhongshu
authors.initials: Z
authors.lastname: Li
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China; Beijing Ditan Hospital, Teaching Hospital of Peking University, Beijing 100015, China.
authors.forename: Shenghu
authors.initials: S
authors.lastname: Feng
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China; Beijing Ditan Hospital, Teaching Hospital of Peking University, Beijing 100015, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China; Beijing Key Laboratory of Emerging Infectious Diseases, Beijing 100015, China. Electronic address: liusa1031@sina.com.
authors.forename: Shunai
authors.initials: S
authors.lastname: Liu
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China; Beijing Key Laboratory of Emerging Infectious Diseases, Beijing 100015, China. Electronic address: chengj0817@sina.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Cheng
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D004268:DNA-Binding Proteins; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000378:metabolism*; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics / Q000378:metabolism; D056564:Sirtuin 1 / Q000378:metabolism*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C425208:PCLAF protein, human; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D002784:Cholesterol; D056564:Sirtuin 1
keywords: FGF21; NS5ATP6; SIRT1; SREBP1; miR-577