title: Conjugated linoleic acid induces hepatic expression of fibroblast growth factor 21 through PPAR-α.
abstract: Fibroblast growth factor 21 (FGF21) is a PPAR-α-regulated metabolic regulator that plays critical roles in glucose homoeostasis, lipid metabolism, insulin sensitivity and obesity. Conjugated linoleic acids (CLA), especially trans-10 (t-10), cis-12 (c-12), have shown anti-obesity properties. In addition, CLA is reported as a high-affinity ligand and activator of PPAR-α. This raises the possibility that FGF21 might be involved in the anti-obesity effect of CLA. In the present study, we tested the hypothesis that FGF21 expression in the liver could be induced by t-10, c-12-CLA through PPAR-α. HepG2 cells were treated with 100 μm-bovine serum albumin, 10 μm-t-10, c-12-CLA or 100 μm-t-10, c-12-CLA for 8 h. A total of ten adult C57BL/6J mice were fed with the diets containing 1 % soya oil or t-10, c-12-CLA for 5 d. t-10, c-12-CLA stimulated hepatic FGF21 mRNA abundance as determined by real-time RT-PCR. t-10, c-12-CLA also increased serum FGF21 concentrations as measured by an ELISA. Co-transfection analysis indicated that reporter gene expression from the mouse FGF21 promoter was induced by t-10, c-12-CLA in a PPAR-α-dependent manner. Taken together, these results suggest that t-10, c-12-CLA induces hepatic FGF21 expression through PPAR-α. This FGF21 and PPAR-α linkage may provide another potential explanation for the anti-obesity effect of t-10, c-12-CLA.
authors.affiliation: Animal Nutrition Institute, Sichuan Agricultural University, Ya'an, Sichuan, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yu
authors.forename: Bing
authors.initials: B
authors.lastname: Yu
authors.forename: Honglin
authors.initials: H
authors.lastname: Jiang
authors.forename: Daiwen
authors.initials: D
authors.lastname: Chen
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000008:administration & dosage / Q000378:metabolism; D016466:CHO Cells; D006224:Cricetinae; D019587:Dietary Supplements; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D017930:Genes, Reporter; D056945:Hep G2 Cells; D006801:Humans; D044243:Linoleic Acids, Conjugated / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D019440:Anti-Obesity Agents; D044243:Linoleic Acids, Conjugated; D047493:PPAR alpha; D012333:RNA, Messenger; D011994:Recombinant Proteins; C414620:fibroblast growth factor 21; C496197:trans-10,cis-12-conjugated linoleic acid; D005346:Fibroblast Growth Factors