Evidence map›Paper›PMID 40837873›Full record

ReviewResearch (Washington, D.C.)2025

Emerging Roles of GDF15 in Metabolic and Cardiovascular Diseases.

Tian Tian, Monan Liu, Peter J Little, Hans Strijdom, Jianping Weng, Suowen Xu

Abstract readReview
In one paragraph

Review in Research (Washington, D.C.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 2 pooled it
–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.

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

21 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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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

6 authors.

Tian TianDepartment of Endocrinology, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China.
Monan LiuDepartment of Endocrinology, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China.
Peter J LittleSchool of Pharmacy and Pharmaceutical Sciences, The University of Queensland, Woolloongabba, QLD4102, Australia.
Hans StrijdomCentre for Cardio-metabolic Research in Africa, Division of Medical Physiology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Jianping WengDepartment of Endocrinology, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China.
Suowen XuDepartment of Endocrinology, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China.ORCID https://orcid.org/0000-0002-5488-5217

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Growth differentiation factor 15 (GDF15), a TGF-β superfamily member and stress-responsive cytokine, plays a critical role in metabolism and regulation of inflammation. This review summarizes the expression, distribution, structure, processing, and secretion of GDF15. We also discuss multilayered regulatory networks governing GDF15 expression, including ATF4/CHOP, AMPK, EGR1, EZH2, PPARγ, NRF2, ERRγ, and p53, as well as posttranscriptional regulator CNOT6L. The GFRAL receptor is central to its function, mediating the anorexigenic and metabolic effects of GDF15. This review synthesizes evidence linking GDF15 to obesity, diabetes, cardiovascular diseases, metabolic liver disorders, cachexia, sarcopenia, and aging while exploring its interactions with key metabolic factors including FGF21, GLP-1, leptin, and glucocorticoids. Lifestyle interventions such as ketogenic, high-fat diets, and exercise modulate GDF15 levels, underscoring its role in pan-metabolic health. Pharmacologically, various agents-including anti-hyperglycemic agents and natural compounds-induce GDF15 expression, implicating their therapeutic potential in cardiometabolic diseases. We comprehensively evaluate current advances in GDF15-targeted drug development, including monoclonal antibodies, fusion proteins, and small-molecule drugs, to provide a scientific foundation for innovative therapies. Finally, we outline unresolved issues in GDF15 biology and therapeutics, such as the exploration of peripheral receptors, contradictory findings in studies of cardiometabolic diseases, and the persistent challenges in developing GDF15-targeted therapeutics.

Identifiers

PMID40837873
PMCPMC12361751

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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 OpenQuestion graph.