Evidence map›Paper›PMID 25043817›Full record

ArticleCell metabolism2014

The PPARα-FGF21 hormone axis contributes to metabolic regulation by the hepatic JNK signaling pathway.

Santiago Vernia, Julie Cavanagh-Kyros, Luisa Garcia-Haro, Guadalupe Sabio, Tamera Barrett, Dae Young Jung, Jason K Kim, Jia Xu, Hennady P Shulha, Manuel Garber and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Cell metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers.

0numbers the graph read from it
0cells of the map it votes in
113citing papers in PubMed
6.1field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

113 citing papers in PubMed, 188 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Attack of the kinases: JNK signaling in metabolism.American journal of physiology. Regulatory, integrative and comparative physiology · 2026
    Review
  6. Mutually exclusive alternative pre-mRNA splicing promotes adaptive metabolic stress signaling by JNK.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. FGF-based drug discovery: advances and challenges.Nature reviews. Drug discovery · 2025
    Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Review
  19. Article
  20. Review

53 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 2 countries.

Santiago VerniaProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Julie Cavanagh-KyrosProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA; Howard Hughes Medical Institute, Worcester, MA 01605, USA.
Luisa Garcia-HaroProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Guadalupe SabioDepartment of Vascular Biology and Inflammation, Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, 28029 Madrid, Spain.
Tamera BarrettProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA; Howard Hughes Medical Institute, Worcester, MA 01605, USA.
Dae Young JungProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Jason K KimProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA; Department of Medicine, Division of Endocrinology, Metabolism and Diabetes, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Jia XuBioinformatics Core, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Hennady P ShulhaBioinformatics Core, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Manuel GarberProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA; Program in Bioinformatics, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Guangping GaoGene Therapy Center, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Roger J DavisProgram 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.
University of Massachusetts Chan Medical School · USHoward Hughes Medical Institute · USSpanish National Centre for Cardiovascular Research · ES

Funding

Systems Biology of Insulin ResistanceR24DK090963 · NIDDK · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI DAVIS, ROGER J. · 2011 to 2014
$8.4M
UMass Mouse Metabolic Phenotyping Center - Metabolism CoreU2CDK093000 · NIDDK · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI KIM, JASON K · 2016 to 2021
$4.6M
UMass Mouse Metabolic Phenotyping CenterU24DK093000 · NIDDK · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI KIM, JASON K · 2011 to 2015
$2.1M
Interleukin-10 and Regulation of Skeletal Muscle Insulin ActionR01DK080756 · NIDDK · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI KIM, JASON K · 2008 to 2012
$1.6M
Transmission Electron Microscope for Core EM FacilityS10RR027897 · NCRR · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI CRAIG, ROGER W · 2009 to 2009
$500k
Scanning Electron Microscope for Core EM FacilityS10RR021043 · NCRR · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI CRAIG, ROGER W · 2007 to 2007
$498k
European Research Council 260464Howard Hughes Medical InstituteNCRR NIH HHS S10 RR021043NCRR NIH HHS S10RR021043NCRR NIH HHS S10 RR027897NCRR NIH HHS S10RR027897NIDDK NIH HHS DK090963NIDDK NIH HHS DK093000NIDDK NIH HHS R01 DK080756NIDDK NIH HHS R24 DK090963NIDDK NIH HHS U24 DK093000
6 · The paper itself

Abstract

The cJun NH2-terminal kinase (JNK) stress signaling pathway is implicated in the metabolic response to the consumption of a high-fat diet, including the development of obesity and insulin resistance. These metabolic adaptations involve altered liver function. Here, we demonstrate that hepatic JNK potently represses the nuclear hormone receptor peroxisome proliferator-activated receptor α (PPARα). Therefore, JNK causes decreased expression of PPARα target genes that increase fatty acid oxidation and ketogenesis and promote the development of insulin resistance. We show that the PPARα target gene fibroblast growth factor 21 (Fgf21) plays a key role in this response because disruption of the hepatic PPARα-FGF21 hormone axis suppresses the metabolic effects of JNK deficiency. This analysis identifies the hepatokine FGF21 as a critical mediator of JNK signaling in the liver.

Indexed as

MAP Kinase Signaling SystemAnimalsDiet, High-FatFibroblast Growth FactorsGene DeletionInsulin ResistanceLiverMaleMAP Kinase Kinase 4MiceMice, Inbred C57BLObesityPPAR alphafibroblast growth factor 21Fibroblast Growth FactorsMAP Kinase Kinase 4PPAR alpha

Identifiers

PMID25043817
PMCPMC4156535
OpenAlexW2069084460

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.