title: Fibroblast Growth Factor 21 Mediates Glycemic Regulation by Hepatic JNK.
abstract: The cJun NH2-terminal kinase (JNK)-signaling pathway is implicated in metabolic syndrome, including dysregulated blood glucose concentration and insulin resistance. Fibroblast growth factor 21 (FGF21) is a target of the hepatic JNK-signaling pathway and may contribute to the regulation of glycemia. To test the role of FGF21, we established mice with selective ablation of the Fgf21 gene in hepatocytes. FGF21 deficiency in the liver caused marked loss of FGF21 protein circulating in the blood. Moreover, the protective effects of hepatic JNK deficiency to suppress metabolic syndrome in high-fat diet-fed mice were not observed in mice with hepatocyte-specific FGF21 deficiency, including reduced blood glucose concentration and reduced intolerance to glucose and insulin. Furthermore, we show that JNK contributes to the regulation of hepatic FGF21 expression during fasting/feeding cycles. These data demonstrate that the hepatokine FGF21 is a key mediator of JNK-regulated metabolic syndrome.
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Santiago
authors.initials: S
authors.lastname: Vernia
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA; Howard Hughes Medical Institute, Worcester, MA 01605, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Cavanagh-Kyros
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA; Howard Hughes Medical Institute, Worcester, MA 01605, USA.
authors.forename: Tamera
authors.initials: T
authors.lastname: Barrett
authors.affiliation: Faculty of Life Sciences, Manchester University, Manchester M13 9PL, UK.
authors.forename: Cathy
authors.initials: C
authors.lastname: Tournier
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA; Howard Hughes Medical Institute, Worcester, MA 01605, USA. Electronic address: roger.davis@umassmed.edu.
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Davis
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002478:Cells, Cultured; D059305:Diet, High-Fat; D005346:Fibroblast Growth Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D007328:Insulin / Q000097:blood; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020738:Leptin / Q000097:blood; D020930:MAP Kinase Kinase Kinases / Q000172:deficiency / Q000235:genetics; D008297:Male; D008659:Metabolic Diseases / Q000209:etiology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000209:etiology / Q000378:metabolism; D063994:Peroxisomal Bifunctional Enzyme / Q000235:genetics / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D052243:Resistin / Q000097:blood; D015398:Signal Transduction; D000097767:Mitogen-Activated Protein Kinase Kinase Kinase 11
chemical_list: D001786:Blood Glucose; D005346:Fibroblast Growth Factors; D007328:Insulin; D048031:JNK Mitogen-Activated Protein Kinases; D020738:Leptin; D020930:MAP Kinase Kinase Kinases; D063994:Peroxisomal Bifunctional Enzyme; D047428:Protein Kinase Inhibitors; D052243:Resistin; D000097767:Mitogen-Activated Protein Kinase Kinase Kinase 11; C414620:fibroblast growth factor 21; C576254:Ehhadh protein, mouse