ArticleThe Biochemical journal2002
Down-regulation of the mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase gene by insulin: the role of the forkhead transcription factor FKHRL1.
Article in The Biochemical journal, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 64 citations in OpenAlex.
- Mitochondrial Dysfunction in Propionic Acidemia: A Case-Report and Review of the Literature.JIMD reports · 2026Article
- JAK2/STAT3/HMGCS2 signaling aggravates mitochondrial dysfunction and oxidative stress in hyperuricemia-induced cardiac dysfunction.Molecular medicine (Cambridge, Mass.) · 2025Article
- Hmgcs2 is the hub gene in diabetic cardiomyopathy and is negatively regulated by Hmgcs2, promoting high glucose-induced cardiomyocyte injury.Immunity, inflammation and disease · 2024Article
- Ketosis Suppression and Ageing (KetoSAge): The Effects of Suppressing Ketosis in Long Term Keto-Adapted Non-Athletic Females.International journal of molecular sciences · 2023Article
- Hmgcs2-mediated ketogenesis modulates high-fat diet-induced hepatosteatosis.Molecular metabolism · 2022Article
- Nutrition, metabolism, and epigenetics: pathways of circadian reprogramming.EMBO reports · 2022Review
- Transcriptional shifts account for divergent resource allocation in feed efficient broiler chickens.Scientific reports · 2018Article
- PTEN: Tumor Suppressor and Metabolic Regulator.Frontiers in endocrinology · 2018Review
- Predictive significance of HMGCS2 for prognosis in resected Chinese esophageal squamous cell carcinoma patients.OncoTargets and therapy · 2017Article
- Regulation of Ketone Body Metabolism and the Role of PPARα.International journal of molecular sciences · 2016Review
- Hepatic adaptations to maintain metabolic homeostasis in response to fasting and refeeding in mice.Nutrition & metabolism · 2016Article
- Transcriptomic analysis to elucidate the molecular mechanisms that underlie feed efficiency in meat-type chickens.Molecular genetics and genomics : MGG · 2015Article
- Decrease in mitochondrial function in rat cardiac permeabilized fibers correlates with the aging phenotype.The journals of gerontology. Series A, Biological sciences and medical sciences · 2010Article
- SIRT1 controls the transcription of the peroxisome proliferator-activated receptor-gamma Co-activator-1alpha (PGC-1alpha) gene in skeletal muscle through the PGC-1alpha autoregulatory loop and interaction with MyoD.The Journal of biological chemistry · 2009Article
- Tumor suppressor Foxo3a is involved in the regulation of lipopolysaccharide-induced interleukin-8 in intestinal HT-29 cells.Infection and immunity · 2008Article
- Parafibromin, a component of the human PAF complex, regulates growth factors and is required for embryonic development and survival in adult mice.Molecular and cellular biology · 2008Article
- Glycogen synthase kinase-3 regulates IGFBP-1 gene transcription through the thymine-rich insulin response element.BMC molecular biology · 2004Article
- Control of cell number by Drosophila FOXO: downstream and feedback regulation of the insulin receptor pathway.Genes & development · 2003Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Normal physiological responses to carbohydrate shortages cause the liver to increase the production of ketone bodies from the acetyl-CoA generated from fatty acid oxidation. This allows the use of ketone bodies for energy, thereby preserving the limited glucose for use by the brain. This adaptative response is switched off by insulin rapidly inhibiting the expression of the mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase (HMGCS2) gene, which is a key control site of ketogenesis. We decided to investigate the molecular mechanism of this inhibition. In the present study, we show that FKHRL1, a member of the forkhead in rhabdosarcoma (FKHR) subclass of the Fox family of transcription factors, stimulates transcription from transfected 3-hydroxy-3-methylglutaryl-CoA synthase promoter-luciferase reporter constructs, and that this stimulation is repressed by insulin. An FKHRL1-responsive sequence AAAAATA, located 211 bp upstream of the HMGCS2 gene transcription start site, was identified by deletion analysis. It binds FKHRL1 in vivo and in vitro and confers FKHRL1 responsiveness on homologous and heterologous promoters. If it is mutated, it partially blocks the effect of insulin in HepG2 cells, both in the absence and presence of overexpressed FKHRL1. These results suggest that FKHRL1 contributes to the regulation of HMGCS2 gene expression by insulin.
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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.