ArticleNature medicine2017
GFRAL is the receptor for GDF15 and the ligand promotes weight loss in mice and nonhuman primates.
Article in Nature medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 480 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
480 citing papers in PubMed, 2 syntheses or guidelines pooled it, 734 citations in OpenAlex.
- Growth differentiation factor 15 as a potential diagnostic biomarker for rheumatoid arthritis : a systematic review.Bone & joint research · 2025Pooled it
- A systematic review of the neuroprotective role and biomarker potential of GDF15 in neurodegeneration.Frontiers in immunology · 2024Pooled it
- Effect of metformin on insulin resistance in adults with type 1 diabetes: a 26-week randomized double-blind clinical trial.Nature communications · 2025 · on this mapTrial
- Growth differentiation factor 15 (GDF15) predicts relapse free and overall survival in unresected locally advanced non-small cell lung cancer treated with chemoradiotherapy.Radiation oncology (London, England) · 2024Trial
- Growth differentiation factor 15 is not modified after weight loss induced by liraglutide in South Asians and Europids with type 2 diabetes mellitus.Experimental physiology · 2024Trial
- Effect of Acute Nutritional Ketosis on Circulating Levels of Growth Differentiation Factor 15: Findings from a Cross-Over Randomised Controlled Trial.Biomolecules · 2024Trial
- Phase 2 study of the efficacy and safety of ponsegromab in patients with cancer cachexia: PROACC-1 study design.Journal of cachexia, sarcopenia and muscle · 2024Trial
- RMND1 dysfunction causes OXPHOS deficiency and alters mitoribosomal protein homeostasis in vivo.EMBO molecular medicine · 2026Article
- Systemic health impact of cancer-associated extracellular vesicles and particles.Nature reviews. Cancer · 2026Review
- Lipid sensing and brain hormone receptors in food intake and glucose regulation.Nature reviews. Endocrinology · 2026Review
- Tumor-Secreted ADAMTSL4 Activates Latent TGFβ1 to Drive Cancer Cachexia.Cancer discovery · 2026Article
- The causes of cachexia: key signals and the brain.Nature reviews. Endocrinology · 2026Review
- Review
- Therapeutic Gfral silencing via antisense oligonucleotides ameliorates cancer-associated cachexia and extends survival in tumor-bearing mice.Cell reports. Medicine · 2026Article
- AAV-NRF2 protects retinal and choroidal vasculature in a GDF15-dependent manner in an oxidative damage model of AMD.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Beneficial Hepatokines in MASLD/MASH: Therapeutic Potentials and Drug Delivery Challenges.International journal of molecular sciences · 2026Review
- Growth Differentiation Factor-15 in Acute Coronary Syndromes: Prognostic Value and Barriers to Clinical Implementation.International journal of molecular sciences · 2026Review
- Novel Endocrine Signaling Axis in Cardiovascular-Kidney-Metabolic Syndrome: Interactions and Therapeutic Potential of FGF21 and GDF15.Journal of cellular biochemistry · 2026Review
- Effectiveness of hochuekkito for colorectal cancer management: protocol for the multicenter randomized controlled AMATERAS study.International journal of colorectal disease · 2026Article
- GDF15 in Liver Fibrosis: Molecular Mechanisms, Immunoregulatory Functions, and Therapeutic Potential.Biomolecules · 2026Review
420 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Growth differentiation factor 15 (GDF15), a distant member of the transforming growth factor (TGF)-β family, is a secreted protein that circulates as a 25-kDa dimer. In humans, elevated GDF15 correlates with weight loss, and the administration of GDF15 to mice with obesity reduces body weight, at least in part, by decreasing food intake. The mechanisms through which GDF15 reduces body weight remain poorly understood, because the cognate receptor for GDF15 is unknown. Here we show that recombinant GDF15 induces weight loss in mice fed a high-fat diet and in nonhuman primates with spontaneous obesity. Furthermore, we find that GDF15 binds with high affinity to GDNF family receptor α-like (GFRAL), a distant relative of receptors for a distinct class of the TGF-β superfamily ligands. Gfral is expressed in neurons of the area postrema and nucleus of the solitary tract in mice and humans, and genetic deletion of the receptor abrogates the ability of GDF15 to decrease food intake and body weight in mice. In addition, diet-induced obesity and insulin resistance are exacerbated in GFRAL-deficient mice, suggesting a homeostatic role for this receptor in metabolism. Finally, we demonstrate that GDF15-induced cell signaling requires the interaction of GFRAL with the coreceptor RET. Our data identify GFRAL as a new regulator of body weight and as the bona fide receptor mediating the metabolic effects of GDF15, enabling a more comprehensive assessment of GDF15 as a potential pharmacotherapy for the treatment of obesity.
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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 OpenQuestion graph.