ArticleProceedings of the National Academy of Sciences of the United States of America2009
PGC-1alpha negatively regulates hepatic FGF21 expression by modulating the heme/Rev-Erb(alpha) axis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
What it found
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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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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
84 citing papers in PubMed, 135 citations in OpenAlex.
- Alterations in 3-Hydroxyisobutyrate and FGF21 Metabolism Are Associated With Protein Ingestion-Induced Insulin Resistance.Diabetes · 2017Trial
- Trial
- Melinjo-derived Gnetin C restores metabolic balance via dual adipose and hepatic effects in high-fat diet mice.Scientific reports · 2025Article
- Association of cerebrospinal fluid FGF21 with sleep quality in Chinese adults.Sleep & breathing = Schlaf & Atmung · 2025Article
- Treating metabolic dysfunction-associated steatohepatitis: The fat-trimming FGF21 approach.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025Review
- Hepatic fibroblast growth factor 21 is required for curcumin or resveratrol in exerting their metabolic beneficial effect in male mice.Nutrition & diabetes · 2025Article
- Hepatic and Pancreatic Cellular Response to Early Life Nutritional Mismatch.Endocrinology · 2025Article
- Deletion of Arntl, a component of the molecular clock, in adipocytes leads to cellular hypertrophy by increasing insulin sensitivity via FGF21.Npj biological timing and sleep · 2025Article
- Dietary caloric input and tumor growth accelerate senescence and modulate liver and adipose tissue crosstalk.Communications biology · 2025Article
- Roles of Growth Hormone-Dependent JAK-STAT5 and Lyn Kinase Signaling in Determining Lifespan and Cancer Incidence.Endocrinology · 2024Article
- Transitions in chromatin conformation shaped by fatty acids and the circadian clock underlie hepatic transcriptional reorganization in obese mice.Cellular and molecular life sciences : CMLS · 2024Article
- Nuclear receptor corepressors non-canonically drive glucocorticoid receptor-dependent activation of hepatic gluconeogenesis.Nature metabolism · 2024Article
- Circadian Regulation of Endocrine Fibroblast Growth Factors on Systemic Energy Metabolism.Molecular pharmacology · 2024Review
- Review
- Recent Advances in Hepatic Metabolic Regulation by the Nuclear Factor Rev-erbɑ.Current drug metabolism · 2024Review
- Targeting NR1D1 in organ injury: challenges and prospects.Military Medical Research · 2023Review
- Recent progress in understanding mitokines as diagnostic and therapeutic targets in hepatocellular carcinoma.World journal of clinical cases · 2023Review
- New insight into ischemic stroke: Circadian rhythm in post-stroke angiogenesis.Frontiers in pharmacology · 2022Review
- The miR-182-5p/FGF21/acetylcholine axis mediates the crosstalk between adipocytes and macrophages to promote beige fat thermogenesis.JCI insight · 2021Article
- Review
24 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
FGF21 is a hormone produced in liver and fat that dramatically improves peripheral insulin sensitivity and lipid metabolism. We show here that obese mice with genetically reduced levels of a key hepatic transcriptional coactivator, PGC-1alpha, have improved whole-body insulin sensitivity with increased levels of hepatic and circulating FGF21. Gain- and loss-of-function studies in primary mouse hepatocytes show that hepatic FGF21 levels are regulated by the expression of PGC-1alpha. Importantly, PGC-1alpha-mediated reduction of FGF21 expression is dependent on Rev-Erbalpha and the expression of ALAS-1. ALAS-1 is a PGC-1alpha target gene and the rate-limiting enzyme in the synthesis of heme, a ligand for Rev-Erbalpha. Modulation of intracellular heme levels mimics the effect of PGC-1alpha on FGF21 expression, and inhibition of heme biosynthesis completely abrogates the down-regulation of FGF21 in response to PGC-1alpha. Thus, PGC-1alpha can impact hepatic and systemic metabolism by regulating the levels of a nuclear receptor ligand.
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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.