ArticleProceedings of the National Academy of Sciences of the United States of America2019
Hepatic posttranscriptional network comprised of CCR4-NOT deadenylase and FGF21 maintains systemic metabolic homeostasis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
What it found
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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
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Exercise-Induced Regulation of Spexin: Implications for Metabolic Health: A Systematic Review and Meta-Analysis.Medicina (Kaunas, Lithuania) · 2026Pooled it
- Posttranscriptional reprogramming controls MASLD progression through chronic ER stress adaptation.Science advances · 2026Article
- Acceleration of Lactate Uptake and Utilization Contributes to Neuroprotective Action of FGF21 Involved in Naturally Aging Mice.Aging cell · 2026Article
- CNOT6 deadenylase safeguards postnatal growth and metabolic transition viabioRxiv : the preprint server for biology · 2026Article
- Review
- Exploring Cirrhosis: Insights into Advances in Therapeutic Strategies.International journal of molecular sciences · 2025Review
- Review
- Emerging Roles of GDF15 in Metabolic and Cardiovascular Diseases.Research (Washington, D.C.) · 2025Review
- High expression of CNOT6L contributes to the negative development of type 2 diabetes.Scientific reports · 2024Article
- The potato RNA metabolism machinery is targeted by the cyst nematode effector RHA1B for successful parasitism.The Plant cell · 2024Article
- Buddleoside-rich Chrysanthemum indicum L. extract modulates macrophage-mediated inflammation to prevent metabolic syndrome induced by unhealthy diet.BMC complementary medicine and therapies · 2024Article
- M2 Macrophage Classification of Colorectal Cancer Reveals Intrinsic Connections with Metabolism Reprogramming and Clinical Characteristics.Pharmacogenomics and personalized medicine · 2024Article
- Targeting FGF21 in cardiovascular and metabolic diseases: from mechanism to medicine.International journal of biological sciences · 2023Review
- Glycerate from intestinal fructose metabolism induces islet cell damage and glucose intolerance.Cell metabolism · 2022Article
- Deadenylase-dependent mRNA decay of GDF15 and FGF21 orchestrates food intake and energy expenditure.Cell metabolism · 2022Article
- ZFP36L1 Regulates Fgf21 mRNA Turnover and Modulates Alcoholic Hepatic Steatosis and Inflammation in Mice.The American journal of pathology · 2022Article
- Anota2seq Analysis for Transcriptome-Wide Studies of mRNA Translation.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Variants inHGG advances · 2021Article
- Crystal structure and functional properties of the human CCR4-CAF1 deadenylase complex.Nucleic acids research · 2021Article
- FGF21 in obesity and cancer: New insights.Cancer letters · 2021Review
Corrections and comments
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Authors and funding
17 authors at 9 institutions in 4 countries.
Funding
Abstract
Whole-body metabolic homeostasis is tightly controlled by hormone-like factors with systemic or paracrine effects that are derived from nonendocrine organs, including adipose tissue (adipokines) and liver (hepatokines). Fibroblast growth factor 21 (FGF21) is a hormone-like protein, which is emerging as a major regulator of whole-body metabolism and has therapeutic potential for treating metabolic syndrome. However, the mechanisms that control FGF21 levels are not fully understood. Herein, we demonstrate that FGF21 production in the liver is regulated via a posttranscriptional network consisting of the CCR4-NOT deadenylase complex and RNA-binding protein tristetraprolin (TTP). In response to nutrient uptake, CCR4-NOT cooperates with TTP to degrade AU-rich mRNAs that encode pivotal metabolic regulators, including FGF21. Disruption of CCR4-NOT activity in the liver, by deletion of the catalytic subunit CNOT6L, increases serum FGF21 levels, which ameliorates diet-induced metabolic disorders and enhances energy expenditure without disrupting bone homeostasis. Taken together, our study describes a hepatic CCR4-NOT/FGF21 axis as a hitherto unrecognized systemic regulator of metabolism and suggests that hepatic CCR4-NOT may serve as a target for devising therapeutic strategies in metabolic syndrome and related morbidities.
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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.