ArticlePloS one2012
Foxa1 reduces lipid accumulation in human hepatocytes and is down-regulated in nonalcoholic fatty liver.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 102 citations in OpenAlex.
- Estradiol mitigates lipid accumulation, oxidative stress, apoptosis, and MAPKs activation in NASH rat model with bilateral orchidectomy.PNAS nexus · 2026Article
- Multi-omics dissection of FOXA1 reveals cancer-type-specific transcriptional networks and functional risk variants.iScience · 2026Article
- Article
- Huangjing Jiangzhi Granules Ameliorate Nonalcoholic Fatty Liver Disease by Activating the FOXA1-DERL1 Regulatory Axis to Suppress Lipid Accumulation, Endoplasmic Reticulum Stress, and Apoptosis.Biological procedures online · 2026Article
- Tumor cell-specific loss of GPX4 reprograms triacylglycerol metabolism to escape ferroptosis and impair antitumor immunity in non-small cell lung cancer.Protein & cell · 2026Article
- CSE Induces Lung Epithelial Cell-derived Exosomal LINC01133-mediated FOXA1 Activity Through SRSF6 to Affect MRC-5 Cellular Lipid Metabolism and Autophagy.Applied biochemistry and biotechnology · 2026Article
- Hepatocyte nuclear factors dynamically regulate triglyceride metabolic reprogramming in metabolic dysfunction-associated steatotic liver disease: Mechanisms and implications.World journal of hepatology · 2025Review
- Anti-dengue activity of a cellular lipid uptake inhibitor, lipofermata.Scientific reports · 2025Article
- Bridging pancreatic and hepatic development: overlapping genes and their role in diabetes.Cellular & molecular biology letters · 2025Review
- The Role of Solute Carrier Family Transporters in Hepatic Steatosis and Hepatic Fibrosis.Journal of clinical and translational hepatology · 2025Review
- Impaired SUMOylation of FoxA1 promotes nonalcoholic fatty liver disease through down-regulation of Sirt6.Cell death & disease · 2024Article
- N-acetyl Cysteine Overdose Induced Acute Toxicity and Hepatic Microvesicular Steatosis by Disrupting GSH and Interfering Lipid Metabolisms in Normal Mice.Antioxidants (Basel, Switzerland) · 2024Article
- Drug-Induced Fatty Liver Disease (DIFLD): A Comprehensive Analysis of Clinical, Biochemical, and Histopathological Data for Mechanisms Identification and Consistency with Current Adverse Outcome Pathways.International journal of molecular sciences · 2024Review
- Unique lipid composition maintained by extracellular blockade leads to prooncogenicity.Cell death discovery · 2024Article
- FOXA1 and FOXA2: the regulatory mechanisms and therapeutic implications in cancer.Cell death discovery · 2024Review
- Trans-omic analysis reveals opposite metabolic dysregulation between feeding and fasting in liver associated with obesity.iScience · 2024Article
- MYC determines lineage commitment in KRAS-driven primary liver cancer development.Journal of hepatology · 2023Article
- Mechanistic Understanding of Idiosyncratic Drug-Induced Hepatotoxicity Using Co-Cultures of Hepatocytes and Macrophages.Antioxidants (Basel, Switzerland) · 2023Article
- The Role of GLP1-RAs in Direct Modulation of Lipid Metabolism in Hepatic Tissue as Determined Using In Vitro Models of NAFLD.Current issues in molecular biology · 2023Review
- Acupoint Catgut Embedding Improves Lipid Metabolism in Exercise-Induced Fatigue Rats via the PPAR Signaling Pathway.Animals : an open access journal from MDPI · 2023Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Triglyceride accumulation in nonalcoholic fatty liver (NAFL) results from unbalanced lipid metabolism which, in the liver, is controlled by several transcription factors. The Foxa subfamily of winged helix/forkhead box (Fox) transcription factors comprises three members which play important roles in controlling both metabolism and homeostasis through the regulation of multiple target genes in the liver, pancreas and adipose tissue. In the mouse liver, Foxa2 is repressed by insulin and mediates fasting responses. Unlike Foxa2 however, the role of Foxa1 in the liver has not yet been investigated in detail. In this study, we evaluate the role of Foxa1 in two human liver cell models, primary cultured hepatocytes and HepG2 cells, by adenoviral infection. Moreover, human and rat livers were analyzed to determine Foxa1 regulation in NAFL. Results demonstrate that Foxa1 is a potent inhibitor of hepatic triglyceride synthesis, accumulation and secretion by repressing the expression of multiple target genes of these pathways (e.g., GPAM, DGAT2, MTP, APOB). Moreover, Foxa1 represses the fatty acid transporter protein FATP2 and lowers fatty acid uptake. Foxa1 also increases the breakdown of fatty acids by inducing peroxisomal fatty acid β-oxidation and ketone body synthesis. Finally, Foxa1 is able to largely up-regulate UCP1, thereby dissipating energy and consistently decreasing the mitochondria membrane potential. We also report that human and rat NAFL have a reduced Foxa1 expression, possibly through a protein kinase C-dependent pathway. We conclude that Foxa1 is an antisteatotic factor that coordinately tunes several lipid metabolic pathways to block triglyceride accumulation in hepatocytes. However, Foxa1 is down-regulated in human and rat NAFL and, therefore, increasing Foxa1 levels could protect from steatosis. Altogether, we suggest that Foxa1 could be a novel therapeutic target for NAFL disease and insulin resistance.
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