title: [Role and mechanism of action of fibroblast growth factor-21 in reducing triglyceride in nonalcoholic fatty liver disease].
abstract: OBJECTIVE
  To investigate the role and mechanism of action of fibroblast growth factor-21 (FGF-21) in reducing triglyceride (TG) in the in vitro and in vivo models of nonalcoholic fatty liver disease (NAFLD).
  
  
  METHODS
  (1) A mixture of free fatty acids was used to establish a model of steatosis in L02 cells, and the cells were treated with various concentrations of FGF-21 or fenofibrate. Twenty-four hours later, oil red O staining was performed to observe the degree of steatosis, and intracellular TG content was determined. RT-PCR and Western blot were applied to measure the mRNA and protein expression of sterol regulatory element-binding protein-1c (SREBP-1c). (2) High-fat diet was used to establish a mouse model of steatosis, and these mice were intraperitoneally injected with FGF-21 or fenofibrate. Eight weeks later, whole blood and liver samples were collected, and HE staining was performed to observe steatosis. Meanwhile, the serum levels of TG, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were measured, and TG content in the liver was also measured. One-way analysis of variance was used for comparison of data between multiple groups, and the least significant difference t-test was used for comparison between any two groups.
  
  
  RESULTS
  (1) Compared with the control group, the model group showed significant steatosis, with significant increases in intracellular lipid droplets and TG content (t = -20.57, P < 0.01), while FGF-21 reduced the number of intracellular lipid droplets and TG content (F = 98.16, P < 0.01) in a dose-dependent manner. In addition, the model group had significantly increased mRNA and protein expression of SREBP-1c compared with the control group (t = -10.73 and -0.1006, both P < 0.01), while FGF-21 down-regulated the mRNA and protein expression of SREBP-1c (F = 161.35 and 36.72, both P < 0.01). (2) Compared with the mice in the control group, those in the model group showed significant steatosis and had significant increases in serum TG level and TG content in the liver (t = -18.84 and 15.71, both P < 0.01). FGF-21 relieved hepatic steatosis and reduced the serum TG level and TG content in the liver (t = 18.11 and 9.46, both P < 0.01). Moreover, FGF-21 reduced the serum levels of ALT and AST in NAFLD mice (t = 25.93 and 12.50, both P < 0.01).
  
  
  CONCLUSIONS
  FGF-21 can inhibit the synthesis of TG through suppressing the expression of SREBP-1c, which further confirms the potential therapeutic effect of FGF-21 in the treatment of NAFLD. This may provide new ideas for the treatment of NAFLD.
authors.affiliation: Second Department of Gastroenterology, Affiliated Qingdao Municipal Hospital of Qingdao University Medical College, Qingdao 266021, China.
authors.forename: Lizhen
authors.initials: L
authors.lastname: Chen
authors.affiliation: Digestive Disease Key Laboratory of Qingdao, Qingdao 266071, China.
authors.forename: Man
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Second Department of Gastroenterology, Affiliated Qingdao Municipal Hospital of Qingdao University Medical College, Qingdao 266021, China.
authors.forename: Yongning
authors.initials: Y
authors.lastname: Xin
authors.affiliation: Second Department of Gastroenterology, Affiliated Qingdao Municipal Hospital of Qingdao University Medical College, Qingdao 266021, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Second Department of Gastroenterology, Affiliated Qingdao Municipal Hospital of Qingdao University Medical College, Qingdao 266021, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Second Department of Gastroenterology, Affiliated Qingdao Municipal Hospital of Qingdao University Medical College, Qingdao 266021, China.
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Second Department of Gastroenterology, Affiliated Qingdao Municipal Hospital of Qingdao University Medical College, Qingdao 266021, China.
authors.forename: Shiying
authors.initials: S
authors.lastname: Xuan
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002460:Cell Line; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D011345:Fenofibrate / Q000494:pharmacology; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D051379:Mice; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000188:drug therapy*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood*
chemical_list: D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D011345:Fenofibrate