Evidence map›Paper›PMID 29753678›Full record

ArticleMolecular metabolism2018

Deficiency of fibroblast growth factor 21 (FGF21) promotes hepatocellular carcinoma (HCC) in mice on a long term obesogenic diet.

Garima Singhal, Gaurav Kumar, Suzanne Chan, Ffolliott M Fisher, Yong Ma, Hilde G Vardeh, Imad A Nasser, Jeffrey S Flier, Eleftheria Maratos-Flier

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular metabolism, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
4.0field-weighted citation impact, top 5% 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

54 citing papers in PubMed, 79 citations in OpenAlex.

  1. Review
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  5. Circulating Inflammation Biomarkers and the Risk of Esophageal Adenocarcinoma: A Nested Case-Control Study in the Department of Defense Serum Repository.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2025
    Article
  6. Treating metabolic dysfunction-associated steatohepatitis: The fat-trimming FGF21 approach.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025
    Review
  7. Article
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  9. Reversion of metabolic dysfunction-associated steatohepatitis by skeletal muscle-directed FGF21 gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Article
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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

9 authors at 3 institutions in 1 country.

Garima SinghalDepartment of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA.
Gaurav KumarEmory Integrated Computational Core, Emory University, Atlanta, GA, 30322, USA.
Suzanne ChanDepartment of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA.
Ffolliott M FisherDepartment of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA.
Yong MaDepartment of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA.
Hilde G VardehDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA.
Imad A NasserDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA.
Jeffrey S FlierDepartment of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA; Department of Neurobiology, Harvard Medical School, Boston, MA, 02215, USA.
Eleftheria Maratos-FlierDepartment of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA. Electronic address: emaratos@bidmc.harvard.edu.
Beth Israel Deaconess Medical Center · USHarvard University · USEmory University · US

Funding

STRUCTURE-FUNCTION RELATIONSHIPS IN THE ALIMENTARY TRACTP30DK034854 · NIDDK · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI JONATHAN C KAGAN · 1986 to 2026
$32.4M
Metabolic Actions of FGF21R01DK028082 · NIDDK · BETH ISRAEL DEACONESS MEDICAL CENTER · PI FLIER, JEFFREY S · 1987 to 2018
$5.0M
NIDDK NIH HHS P30 DK034854NIDDK NIH HHS R01 DK028082
6 · The paper itself

Abstract

objectiveNon-alcoholic fatty liver (NAFL) associated with obesity is a major cause of liver diseases which can progress to non-alcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Fibroblast growth factor 21 (FGF21) plays an important role in liver metabolism and is also a potential marker for NAFL. Here we aimed to test the effect of FGF21 deficiency on liver pathology in mice consuming a conventional high fat, high sucrose (HFHS) obesogenic diet for up to 52 weeks.

methodsC57BL6 WT and FGF21 KO mice were fed a conventional obesogenic diet and were evaluated at 16 and 52 weeks. Evaluation included metabolic assessment, liver pathology, and transcriptomic analysis.

resultsWith consumption of HFHS diet, FGF21 deficient mice (FGF21 KO) develop excess fatty liver within 16 weeks. Hepatic pathology progresses and at 52 weeks FGF21 KO mice show significantly worse fibrosis and 78% of mice develop HCC; in contrast only 6% of WT mice develop HCC. Well differentiated hepatocellular carcinomas in FGF21 KO mice were characterized by expanded hepatic plates, loss of reticulin network, cytologic atypia, and positive immunostaining for glutamine synthetase. Microarray analysis reveals enrichment of several fibroblast growth factor signaling pathways in the tumors.

conclusionsIn addition to attenuating inflammation and fibrosis in mice under a number of dietary challenges, we show here that FGF21 is required to limit the progression from NAFL to HCC in response to prolonged exposure to an obesogenic diet. The induction of hepatic FGF21 in response to the high fat, high sucrose obesogenic diet may play an important role in limiting progression of liver pathology from NAFL to HCC.

Indexed as

AnimalsCarcinoma, HepatocellularDiet, High-FatFibroblast Growth FactorsLiverLiver CirrhosisLiver NeoplasmsMaleMiceMice, Inbred C57BLMice, KnockoutNon-alcoholic Fatty Liver DiseaseObesityfibroblast growth factor 21Fibroblast Growth FactorsFibroblast growth factor 21Hepatocellular carcinomaHigh fat high sucrose dietLiver fibrosisNonalcoholic fatty liver diseaseNonalcoholic steatohepatitis

Identifiers

PMID29753678
PMCPMC6026320
OpenAlexW2791134623

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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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.