Evidence mapPaperPMID 40527315Full record

ArticleCell metabolism2025

FGF21 promotes longevity in diet-induced obesity through metabolic benefits independent of growth suppression.

Christy M Gliniak, Ruth Gordillo, Yun-Hee Youm, Qian Lin, Clair Crewe, Zhuzhen Zhang, Bianca C Field, Teppei Fujikawa, Megan Virostek, Shangang Zhao and 5 more

Registry-linked trialAbstract read
In one paragraph

Article in Cell metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07113418 (Role of Fibroblast Growth Factor 21), which is not on this map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
field-weighted citation impact
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.

NCT07113418 not yet recruitingnot on this map

Role of Fibroblast Growth Factor 21(FGF21) in Breast Cancer

Typeobservational_patient_registrySponsorAssiut UniversityRan2025 to 2026Enrolled84ConditionsBreast CancerArmsELISA
3 · Its place in the literature

Who cites it

16 citing papers in PubMed.

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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

15 authors.

Christy M GliniakTouchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Ruth GordilloTouchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Yun-Hee YoumDepartment of Pathology, Immunobiology and Comparative Medicine, Yale Center for Research on Aging (Y-Age), Yale School of Medicine, New Haven, CT, USA.
Qian LinTouchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Clair CreweTouchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Cell Biology and Physiology and the Department of Internal Medicine, Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, St. Louis, MO, USA.
Zhuzhen ZhangTouchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas, TX, USA; College of Life Sciences, Wuhan University, Wuhan, China.
Bianca C FieldTouchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Teppei FujikawaCenter for Hypothalamic Research, Department of Internal Medicine and the Peter O'Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA; Institute of Human Life and Ecology, Osaka Metropolitan University, Osaka, Japan.
Megan VirostekTouchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Shangang ZhaoTouchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas, TX, USA; Sam and Ann Barshop Institute for Longevity and Aging Studies, Division of Endocrinology, Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
Yi ZhuTouchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Clifford J RosenCenter for Molecular Medicine, MaineHealth Institute for Research, Scarborough, ME, USA.
Tamas L HorvathDepartment of Comparative Medicine, Yale School of Medicine, New Haven, CT, USA; Department of Anatomy and Histology, University of Veterinary Medicine, Budapest 1078, Hungary.
Vishwa Deep DixitDepartment of Pathology, Immunobiology and Comparative Medicine, Yale Center for Research on Aging (Y-Age), Yale School of Medicine, New Haven, CT, USA.
Philipp E SchererTouchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address: philipp.scherer@utsouthwestern.edu.

Funding

Yale Diabetes Research CenterP30DK045735 · YALE UNIVERSITY · 1993 to 2025
$10.2M
The role of AgRP/Auga-ALK pathway in FGF21's brain action on agingP01AG051459 · YALE UNIVERSITY · 2025 to 2025
$2.4M
ACRP, A PROTEIN SECRETED FROM ADIPOSE TISSUER01DK055758 · YESHIVA UNIVERSITY · 2000 to 2005
$2.0M
Yale Murine-TMC on Immune Cell Senescence Derived InflammationU54AG079759 · YALE UNIVERSITY · 2025 to 2025
$1.6M
Physiological Role of Dedifferentiating Dermal Adipose TissueR01DK131537 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · 2023 to 2025
$1.5M
UT Southwestern NORCP30DK127984 · UT SOUTHWESTERN MEDICAL CENTER · 2025 to 2025
$1.2M
A New Perspective on Leptin in Health and DiseaseR01DK127274 · UT SOUTHWESTERN MEDICAL CENTER · 2025 to 2025
$809k
Effects of leptin modulation on health span and lifespanR01AG084646 · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2025 to 2025
$640k
White Adipose Tissue Physiology, Mitochondrial Function and AdiponectinR01DK099110 · UT SOUTHWESTERN MEDICAL CENTER · 2025 to 2025
$624k
Hypothalamic MC4Rs and Antipsychotic Drug-Induced Metabolic SyndromeR01DK114036 · UT SOUTHWESTERN MEDICAL CENTER · 2025 to 2025
$486k
Enhancing metabolic action of FGF21 through adipocyte Connexin43 gap junction channelsR01DK136619 · BAYLOR COLLEGE OF MEDICINE · 2025 to 2025
$452k
Postprandial activation of hyaluronan-MARCO axis contributes to systemic chronic inflammationR01DK136532 · BAYLOR COLLEGE OF MEDICINE · 2025 to 2025
$434k
NIA NIH HHS P01 AG051459NIA NIH HHS R00 AG068239NIA NIH HHS R01 AG068863NIA NIH HHS R01 AG084646NIA NIH HHS U54 AG079759NIDDK NIH HHS K01 DK131252NIDDK NIH HHS P30 DK045735NIDDK NIH HHS P30 DK127984NIDDK NIH HHS R00 DK122019NIDDK NIH HHS R01 DK055758NIDDK NIH HHS R01 DK099110NIDDK NIH HHS R01 DK114036NIDDK NIH HHS R01 DK127274NIDDK NIH HHS R01 DK131537NIDDK NIH HHS R01 DK136532NIDDK NIH HHS R01 DK136619NIDDK NIH HHS R01 DK138035NIDDK NIH HHS RC2 DK118620
6 · The paper itself

Abstract

Approximately 35% of US adults over 65 are obese, highlighting the need for therapies targeting age-related metabolic issues. Fibroblast growth factor 21 (FGF21), a hormone mainly produced by the liver, improves metabolism and extends lifespan. To explore its effects without developmental confounders, we generated mice with adipocyte-specific FGF21 overexpression beginning in adulthood. When fed a high-fat diet, these mice lived up to 3.3 years, resisted weight gain, improved insulin sensitivity, and showed reduced liver steatosis. Aged transgenic mice also displayed lower levels of inflammatory immune cells and lipotoxic ceramides in visceral adipose tissue, benefits that occurred even in the absence of adiponectin, a hormone known to regulate ceramide breakdown. These results suggest that fat tissue is a central site for FGF21's beneficial effects and point to its potential for treating metabolic syndrome and age-related diseases by promoting a healthier metabolic profile under dietary stress and extending healthspan and lifespan.

Indexed as

Fibroblast Growth FactorsLongevityObesityAdipocytesAdiponectinAnimalsCeramidesDiet, High-FatFatty LiverInsulin ResistanceLiverMaleMiceMice, Inbred C57BLMice, TransgenicAdiponectinCeramidesfibroblast growth factor 21Fibroblast Growth Factorsadipocytesadiponectinadipose tissueagingceramidesFGF21inflammationinsulin sensitivitylongevityobesity

Identifiers

PMID40527315
PMCPMC12221793

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

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.