ArticleCell metabolism2022
Deadenylase-dependent mRNA decay of GDF15 and FGF21 orchestrates food intake and energy expenditure.
Article in Cell metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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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.
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Who cites it
34 citing papers in PubMed, 55 citations in OpenAlex.
- Moderate iron restriction improves metabolism via epigenetic regulation of GDF15.The Journal of nutritional biochemistry · 2026Article
- Novel Endocrine Signaling Axis in Cardiovascular-Kidney-Metabolic Syndrome: Interactions and Therapeutic Potential of FGF21 and GDF15.Journal of cellular biochemistry · 2026Review
- Transcriptomic Analysis in the Liver of Two Rabbit Lines Divergently Selected for Intramuscular Fat Content.Animal genetics · 2026Article
- Hepatocyte SLCO4C1 is a cAMP uptake transporter for inhibiting lipogenesis and a therapeutic target for MASLD.Nature communications · 2026Article
- CNOT6 deadenylase safeguards postnatal growth and metabolic transition viabioRxiv : the preprint server for biology · 2026Article
- Selective β3-adrenoceptor agonist reduces energy intake and elevates GDF15 levels in lean and diet-induced obese mice.Endocrine journal · 2026Article
- Cancer-cell-secreted DDAH1 induces TGF-β1/Smad3 signaling pathway to promote fibrosis and aging in lung.Nature aging · 2026Article
- Mitohormesis linking metabolic dysfunction and neurodegeneration: implications for dementia and therapeutic strategies.Frontiers in molecular neuroscience · 2026Review
- Hypoxia-mediated regulation of mRNA metabolism: from transcription to stability.Cell communication and signaling : CCS · 2025Review
- Revisiting the role of GDF15 in atherosclerosis in mouse and human.Acta pharmacologica Sinica · 2025Article
- The clinical antiprotozoal drug halofuginone promotes weight loss by elevating GDF15 and FGF21.Science advances · 2025Article
- GDF15-mediated enhancement of the Warburg effect sustains multiple myeloma growth via TGFβ signaling pathway.Cancer & metabolism · 2025Article
- Review
- Emerging Roles of GDF15 in Metabolic and Cardiovascular Diseases.Research (Washington, D.C.) · 2025Review
- CNOT6L regulates energy metabolism in the ovarian granulosa cells associated with polycystic ovary syndrome.Frontiers in cell and developmental biology · 2025Article
- Cnot4 heterozygosity attenuates high fat diet-induced obesity in mice and impairs PPARγ-mediated adipocyte differentiation.PloS one · 2025Article
- Databases of ligand-binding pockets and protein-ligand interactions.Computational and structural biotechnology journal · 2024Review
- Targeting the GDF15 Signalling for Obesity Treatment: Recent Advances and Emerging Challenges.Journal of cellular and molecular medicine · 2024Review
- Hepatocyte-specific GDF15 overexpression improves high-fat diet-induced obesity and hepatic steatosis in mice via hepatic FGF21 induction.Scientific reports · 2024Article
- Integrative analysis of the transcriptome and metabolome reveals the importance of hepatokine FGF21 in liver aging.Genes & diseases · 2024Article
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Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
Abstract
Hepatokines, secretory proteins from the liver, mediate inter-organ communication to maintain a metabolic balance between food intake and energy expenditure. However, molecular mechanisms by which hepatokine levels are rapidly adjusted following stimuli are largely unknown. Here, we unravel how CNOT6L deadenylase switches off hepatokine expression after responding to stimuli (e.g., exercise and food) to orchestrate energy intake and expenditure. Mechanistically, CNOT6L inhibition stabilizes hepatic Gdf15 and Fgf21 mRNAs, increasing corresponding serum protein levels. The resulting upregulation of GDF15 stimulates the hindbrain to suppress appetite, while increased FGF21 affects the liver and adipose tissues to induce energy expenditure and lipid consumption. Despite the potential of hepatokines to treat metabolic disorders, their administration therapies have been challenging. Using small-molecule screening, we identified a CNOT6L inhibitor enhancing GDF15 and FGF21 hepatokine levels, which dramatically improves diet-induced metabolic syndrome. Our discovery, therefore, lays the foundation for an unprecedented strategy to treat metabolic syndrome.
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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.