ArticleNature medicine2017
The metabolic effects of GDF15 are mediated by the orphan receptor GFRAL.
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 414 papers, 4 of them syntheses that pooled it.
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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.
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.
Who cites it
414 citing papers in PubMed, 4 syntheses or guidelines pooled it, 634 citations in OpenAlex.
- Growth differentiation factor 15 as a potential diagnostic biomarker for rheumatoid arthritis : a systematic review.Bone & joint research · 2025Pooled it
- Circulating growth differentiation factor-15 concentration and hypertension risk: a dose-response meta-analysis.Frontiers in cardiovascular medicine · 2025Pooled it
- A systematic review of the neuroprotective role and biomarker potential of GDF15 in neurodegeneration.Frontiers in immunology · 2024Pooled it
- Association between growth differentiation factor 15 levels and gestational diabetes mellitus: A combined analysis.Frontiers in endocrinology · 2023Pooled it
- Metformin increases glycolysis and the stress-induced cytokine GDF15 but not FGF21 in humans.Frontiers in endocrinology · 2026Trial
- Effects of a two-week modified ketogenic diet on circulating lipoprotein subclasses, GDF15, and FGF21 in obese adults.Journal of translational medicine · 2025Trial
- 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
- 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
- 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
- Cancer Cachexia in Advanced Renal Cell Carcinoma: From Molecular Mechanisms to Prognostic Assessment.International journal of molecular sciences · 2026Review
- Tumour GDF-15 Expression and Clinical Outcomes in Intermediate-Risk Metastatic Clear-Cell Renal Cell Carcinoma Treated with Second-Line Nivolumab.Current oncology (Toronto, Ont.) · 2026Article
- Integrated miRNA-cytokine profiling reveals a molecular signature of cachexia in patients with chronic heart failure.ESC heart failure · 2026Article
- Emerging Myostatin and Metabolic Hormone Pathway Modulators in Cardiometabolic Disease: Mechanisms, Evidence, and Therapeutic Potential.Journal of cardiovascular translational research · 2026Review
- 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
- 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
354 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
24 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Growth/differentiation factor 15 (GDF15), also known as MIC-1, is a distant member of the transforming growth factor-β (TGF-β) superfamily and has been implicated in various biological functions, including cancer cachexia, renal and heart failure, atherosclerosis and metabolism. A connection between GDF15 and body-weight regulation was initially suggested on the basis of an observation that increasing GDF15 levels in serum correlated with weight loss in individuals with advanced prostate cancer. In animal models, overexpression of GDF15 leads to a lean phenotype, hypophagia and other improvements in metabolic parameters, suggesting that recombinant GDF15 protein could potentially be used in the treatment of obesity and type 2 diabetes. However, the signaling and mechanism of action of GDF15 are poorly understood owing to the absence of a clearly identified cognate receptor. Here we report that GDNF-family receptor α-like (GFRAL), an orphan member of the GFR-α family, is a high-affinity receptor for GDF15. GFRAL binds to GDF15 in vitro and is required for the metabolic actions of GDF15 with respect to body weight and food intake in vivo in mice. Gfral
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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.