Evidence mapPaperPMID 34192547Full record

ArticleCell reports2021

FGF21 promotes thermogenic gene expression as an autocrine factor in adipocytes.

Mohammad Abu-Odeh, Yuan Zhang, Shannon M Reilly, Nima Ebadat, Omer Keinan, Joseph M Valentine, Maziar Hafezi-Bakhtiari, Hadeel Ashayer, Lana Mamoun, Xin Zhou and 9 more

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed
5.8field-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

56 citing papers in PubMed, 94 citations in OpenAlex.

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  18. PGC-1α Activation by Polyphenols: A Pathway to Thermogenesis.Molecular nutrition & food research · 2025
    Review
  19. FGF-based drug discovery: advances and challenges.Nature reviews. Drug discovery · 2025
    Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 4 institutions in 2 countries.

Mohammad Abu-OdehDepartment of Medicine, University of California, San Diego, San Diego, CA 92093, USA.
Yuan ZhangDepartment of Pharmacology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Shannon M ReillyDepartment of Medicine, University of California, San Diego, San Diego, CA 92093, USA.
Nima EbadatDepartment of Medicine, University of California, San Diego, San Diego, CA 92093, USA.
Omer KeinanDepartment of Medicine, University of California, San Diego, San Diego, CA 92093, USA.
Joseph M ValentineDepartment of Medicine, University of California, San Diego, San Diego, CA 92093, USA.
Maziar Hafezi-BakhtiariDepartment of Medicine, University of California, San Diego, San Diego, CA 92093, USA.
Hadeel AshayerDepartment of Medicine, University of California, San Diego, San Diego, CA 92093, USA.
Lana MamounDepartment of Medicine, University of California, San Diego, San Diego, CA 92093, USA.
Xin ZhouDepartment of Pharmacology, University of California, San Diego, San Diego, CA 92093, USA.
Jin ZhangDepartment of Pharmacology, University of California, San Diego, San Diego, CA 92093, USA; Moores Cancer Center at UC San Diego Health, La Jolla, CA 92037, USA; Department of Bioengineering, University of California San Diego, San Diego, CA 92093; Department of Chemistry and Biochemistry, University of California San Diego, San Diego, CA 92093, USA.
Ruth T YuGene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Yang DaiGene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Christopher LiddleStorr Liver Centre, Westmead Institute for Medical Research and Sydney Medical School, University of Sydney, Westmead, NSW, Australia.
Michael DownesGene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Ronald M EvansGene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Steven A KliewerDepartment of Pharmacology, UT Southwestern Medical Center, Dallas, TX 75390, USA; Department of Molecular Biology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
David J MangelsdorfDepartment of Pharmacology, UT Southwestern Medical Center, Dallas, TX 75390, USA; Howard Hughes Medical Institute.
Alan R SaltielDepartment of Medicine, University of California, San Diego, San Diego, CA 92093, USA; Department of Pharmacology, University of California, San Diego, San Diego, CA 92093, USA. Electronic address: asaltiel@health.ucsd.edu.
University of California, San Diego · USSalk Institute for Biological Studies · USSouthwestern Medical Center · USWestmead Institute for Medical Research · AU

Funding

Viral Vector Core (VVC)P30CA014195 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · 1985 to 2025
$37.5M
Yeast Genetics and Stress Response Genes-BiomedicalP42ES010337 · UNIVERSITY OF CALIFORNIA SAN DIEGO · 2000 to 2005
$19.5M
Pilot & Feasibility ProgramP30DK063491 · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2003 to 2025
$5.4M
HORMONAL REGULATION OF MAMMALIAN GENE EXPRESSIONR37DK057978 · SALK INSTITUTE FOR BIOLOGICAL STUDIES · 2000 to 2005
$4.2M
The role of AgRP/Auga-ALK pathway in FGF21's brain action on agingP01AG051459 · YALE UNIVERSITY · 2025 to 2025
$2.4M
Regulation of fatty acid metabolism in adipocytesR01DK126944 · NIDDK · WEILL MEDICAL COLL OF CORNELL UNIV · 2022 to 2025
$1.3M
Regulation of glycogen in health and diseaseR01DK117551 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 to 2025
$914k
EXPERIMENTAL ENDOCRINOLOGY AND METABOLISMT32DK007044 · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 1986 to 2025
$882k
Protection of Intestine by the Bile Acid Receptor FXRR01DK067158 · UNIVERSITY OF TEXAS SW MED CTR/DALLAS · 2004 to 2005
$549k
Mechanisms of Compartmentalized cAMP SignalingR01DK073368 · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2025 to 2025
$406k
Howard Hughes Medical InstituteNCI NIH HHS P30 CA014195NIAAA NIH HHS R01 AA028473NIA NIH HHS P01 AG051459NIDDK NIH HHS F32 DK124947NIDDK NIH HHS K01 DK105075NIDDK NIH HHS P30 DK063491NIDDK NIH HHS R01 DK057978NIDDK NIH HHS R01 DK067158NIDDK NIH HHS R01 DK073368NIDDK NIH HHS R01 DK076906NIDDK NIH HHS R01 DK117551NIDDK NIH HHS R01 DK120480NIDDK NIH HHS R01 DK122804NIDDK NIH HHS R01 DK124496NIDDK NIH HHS R01 DK125820NIDDK NIH HHS R01 DK126944NIDDK NIH HHS R03 DK118195NIDDK NIH HHS R37 DK057978NIDDK NIH HHS T32 DK007044NIEHS NIH HHS P42 ES010337
6 · The paper itself

Abstract

The contribution of adipose-derived FGF21 to energy homeostasis is unclear. Here we show that browning of inguinal white adipose tissue (iWAT) by β-adrenergic agonists requires autocrine FGF21 signaling. Adipose-specific deletion of the FGF21 co-receptor β-Klotho renders mice unresponsive to β-adrenergic stimulation. In contrast, mice with liver-specific ablation of FGF21, which eliminates circulating FGF21, remain sensitive to β-adrenergic browning of iWAT. Concordantly, transgenic overexpression of FGF21 in adipocytes promotes browning in a β-Klotho-dependent manner without increasing circulating FGF21. Mechanistically, we show that β-adrenergic stimulation of thermogenic gene expression requires FGF21 in adipocytes to promote phosphorylation of phospholipase C-γ and mobilization of intracellular calcium. Moreover, we find that the β-adrenergic-dependent increase in circulating FGF21 occurs through an indirect mechanism in which fatty acids released by adipocyte lipolysis subsequently activate hepatic PPARα to increase FGF21 expression. These studies identify FGF21 as a cell-autonomous autocrine regulator of adipose tissue function.

Indexed as

Autocrine CommunicationGene Expression Regulation3T3-L1 CellsAdipocytesAdipose Tissue, BrownAdipose Tissue, WhiteAdrenergic beta-AgonistsAnimalsFibroblast Growth FactorsLipolysisLiverMiceOrgan SpecificityProtein BindingReceptors, Adrenergic, beta-3Receptors, Fibroblast Growth FactorAdrenergic beta-Agonistsfibroblast growth factor 21Fibroblast Growth FactorsReceptors, Adrenergic, beta-3Receptors, Fibroblast Growth FactorRNA, MessengeradiposeadrenergicautocrinebeigeBeigingBrowningFGF21thermogenic

Identifiers

PMID34192547
PMCPMC8293281
OpenAlexW3174562054

What Socratic holds

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Registered trials

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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 Socratic graph.