UMMS Affiliation
Program in Molecular Medicine; UMass Metabolic Network
Publication Date
2016-03-15
Document Type
Article
Disciplines
Biochemistry | Cell Biology | Cellular and Molecular Physiology | Molecular Biology
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.
Rights and Permissions
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
DOI of Published Version
10.1016/j.celrep.2016.02.026
Source
Cell Rep. 2016 Mar 15;14(10):2273-80. doi: 10.1016/j.celrep.2016.02.026. Epub 2016 Mar 3. Link to article on publisher's site
Journal/Book/Conference Title
Cell reports
Related Resources
PubMed ID
26947074
Repository Citation
Vernia, Santiago; Cavanagh-Kyros, Julie; Barrett, Tamera; Tournier, Cathy; and Davis, Roger J., "Fibroblast Growth Factor 21 Mediates Glycemic Regulation by Hepatic JNK" (2016). Davis Lab Publications. 54.
https://escholarship.umassmed.edu/davis/54
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Included in
Biochemistry Commons, Cell Biology Commons, Cellular and Molecular Physiology Commons, Molecular Biology Commons