ArticleProceedings of the National Academy of Sciences of the United States of America2003
Regulation of hepatic fasting response by PPARgamma coactivator-1alpha (PGC-1): requirement for hepatocyte nuclear factor 4alpha in gluconeogenesis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 265 papers, 1 of them a synthesis that pooled it.
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Who cites it
265 citing papers in PubMed, 1 synthesis or guideline pooled it, 571 citations in OpenAlex.
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- Effects of Weight Loss on FGF-21 in Human Subjects: An Exploratory Study.International journal of environmental research and public health · 2019Trial
- A pharmacogenetic association between a variation in calpain 10 (CAPN10) gene and the response to metformin treatment in patients with type 2 diabetes.European journal of clinical pharmacology · 2015 · on this mapTrial
- Transcriptional signatures related to glucose and lipid metabolism predict treatment response to the tumor necrosis factor antagonist infliximab in patients with treatment-resistant depression.Brain, behavior, and immunity · 2013Trial
- Common variants in 40 genes assessed for diabetes incidence and response to metformin and lifestyle intervention in the diabetes prevention program.Diabetes · 2010 · on this mapTrial
- Divergent Hypoxia-Inducible Factor 2‑Alpha Signaling in Alcoholic Liver Disease and Metabolic Dysfunction-Associated Steatotic Liver Disease.ACS pharmacology & translational science · 2026Review
- Hypoxia Promotes Gluconeogenesis Through PGC-1α in the Liver of Lasiopodomys brandtii.Integrative zoology · 2026Article
- Molecular regulation of PGC-1α: from protein-protein interactions and post-translational modifications to pharmacological modulation.Journal of molecular medicine (Berlin, Germany) · 2026Review
- A non-enzymatic function of neuraminidase 1 restrains hepatic glucagon response in mice.Nature communications · 2026Article
- Fasting-Induced Changes in Serum Kynurenines Do Not Always Reflect Their Urinary Excretion.Nutrients · 2026Article
- Hepatic Glucocorticoid Receptor Action and Glucose Homeostasis.Endocrine reviews · 2026Review
- Inhibition of hepatic gluconeogenesis in type 2 diabetes by metformin: complementary role of nitric oxide.Medical gas research · 2025Review
- Impaired mitochondria-initiated crosstalk with lysosomes reciprocally aggravates mitochondrial defect through LManVI.Nature communications · 2025Article
- Article
- Identification of IL-34 and Slc7al as potential key regulators in MASLD progression through epigenomic profiling.Epigenomics · 2025Article
- Non-catalytic mechanisms of KMT5C regulating hepatic gluconeogenesis.Nature communications · 2025Article
- Insights of direct and indirect regulation of PXR through phosphorylation in fatty liver disease.Molecular pharmacology · 2025Review
- The Role of microRNA-22 in Metabolism.International journal of molecular sciences · 2025Review
- 5-Hydroxytryptamine 1F Receptor Agonist Lasmiditan Differentially Regulates Successful Repair and Failed Repair Genes in a Mouse Model of Acute Kidney Injury.ACS pharmacology & translational science · 2024Article
- Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family in physiological and pathophysiological process and diseases.Signal transduction and targeted therapy · 2024Review
205 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
The liver plays several critical roles in the metabolic adaptation to fasting. We have shown previously that the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) is induced in fasted or diabetic liver and activates the entire program of gluconeogenesis. PGC-1alpha interacts with several nuclear receptors known to bind gluconeogenic promoters including the glucocorticoid receptor, hepatocyte nuclear factor 4alpha (HNF4alpha), and the peroxisome proliferator-activated receptors. However, the genetic requirement for any of these interactions has not been determined. Using hepatocytes from mice lacking HNF4alpha in the liver, we show here that PGC-1alpha completely loses its ability to activate key genes of gluconeogenesis such as phosphoenolpyruvate carboxykinase and glucose-6-phosphatase when HNF4alpha is absent. It is also shown that PGC-1alpha can induce genes of beta-oxidation and ketogenesis in hepatocytes, but these effects do not require HNF4alpha. Analysis of the glucose-6-phosphatase promoter indicates a key role for HNF4alpha-binding sites that function robustly only when HNF4alpha is coactivated by PGC-1alpha. These data illustrate the involvement of PGC-1alpha in several aspects of the hepatic fasting response and show that HNF4alpha is a critical component of PGC-1alpha-mediated gluconeogenesis.
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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.