title: Fibroblast growth factor-21 and the beneficial effects of long-chain n-3 polyunsaturated fatty acids.
abstract: Long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) in the diet protect against insulin resistance and obesity. Fibroblast growth factor-21 (Fgf21) is a hormonal factor released mainly by the liver that has powerful anti-diabetic effects. Here, we tested whether the beneficial metabolic effects of LC n-3 PUFA involve the induction of Fgf21. C57BL/6 J mice were exposed to an obesogenic, corn-oil-based, high-fat diet (cHF), or a diet in which corn oil was replaced with a fish-derived LC n-3 PUFA concentrate (cHF + F) using two experimental settings: short-term (3 weeks) and long-term treatment (8 weeks). CHF + F reduced body weight gain, insulinemia, and triglyceridemia compared to cHF. cHF increased plasma Fgf21 levels and hepatic Fgf21 gene expression compared with controls, but these effects were less pronounced or absent in cHF + F-fed mice. In contrast, hepatic expression of peroxisome proliferator-activated receptor (PPAR)-α target genes were more strongly induced by cHF + F than cHF, especially in the short-term treatment setting. The expression of genes encoding Fgf21, its receptors, and Fgf21 targets was unaltered by short-term LC n-3 PUFA treatment, with the exception of Ucp1 (uncoupling protein 1) and adiponectin genes, which were specifically up-regulated in white fat. In the long-term treatment setting, the expression of Fgf21 target genes and receptors was not differentially affected by LC n-3 PUFA. Collectively, our findings indicate that increased Fgf21 levels do not appear to be a major mechanism through which LC n-3 PUFA ameliorates high-fat-diet-associated metabolic disorders.
authors.affiliation: Departament de Bioquimica i Biologia Molecular, Institut de Biomedicina de la Universitat de Barcelona (IBUB), University of Barcelona, Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Villarroya
authors.forename: Pavel
authors.initials: P
authors.lastname: Flachs
authors.forename: Ibon
authors.initials: I
authors.lastname: Redondo-Angulo
authors.forename: Marta
authors.initials: M
authors.lastname: Giralt
authors.forename: Dasa
authors.initials: D
authors.lastname: Medrikova
authors.forename: Francesc
authors.initials: F
authors.lastname: Villarroya
authors.forename: Jan
authors.initials: J
authors.lastname: Kopecky
authors.forename: Anna
authors.initials: A
authors.lastname: Planavila
mesh_terms: D052242:Adiponectin / Q000235:genetics; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003314:Corn Oil / Q000008:administration & dosage; D059305:Diet, High-Fat; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000494:pharmacology*; D005346:Fibroblast Growth Factors / Q000097:blood* / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects*; D007328:Insulin / Q000097:blood; D007473:Ion Channels / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000235:genetics; D047493:PPAR alpha / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014280:Triglycerides / Q000097:blood; D000071256:Uncoupling Protein 1; D015854:Up-Regulation / Q000187:drug effects; D015430:Weight Gain / Q000187:drug effects
chemical_list: D052242:Adiponectin; D015525:Fatty Acids, Omega-3; D007328:Insulin; D007473:Ion Channels; D024101:Mitochondrial Proteins; D047493:PPAR alpha; D014280:Triglycerides; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D003314:Corn Oil