ArticleThe Journal of clinical investigation2008
FoxO1 mediates insulin-dependent regulation of hepatic VLDL production in mice.
Article in The Journal of clinical investigation, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 146 papers.
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The trial behind it
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Who cites it
146 citing papers in PubMed, 279 citations in OpenAlex.
- The dual glucose-dependent insulinotropic peptide and glucagon-like peptide-1 receptor agonist, tirzepatide, improves lipoprotein biomarkers associated with insulin resistance and cardiovascular risk in patients with type 2 diabetes.Diabetes, obesity & metabolism · 2020Trial
- A randomized 3-way crossover study indicates that high-protein feeding induces de novo lipogenesis in healthy humans.JCI insight · 2019Trial
- One day of mixed meal overfeeding reduces hepatic insulin sensitivity and increases VLDL particle but not VLDL-triglyceride secretion in overweight and obese men.The Journal of clinical endocrinology and metabolism · 2013Trial
- Liver-specific delivery of MDM2 antisense oligonucleotides counteracts diet-induced metabolic-dysfunction-associated steatotic liver diseases.Molecular therapy. Nucleic acids · 2026Article
- FOXO6 activation promotes hepatic steatosis via PPARα inhibition in aged male rats.BMB reports · 2026Article
- Association of Metabolic Syndrome and Cholelithiasis: Understanding the Underlying Mechanism for Better Treatment.Mini reviews in medicinal chemistry · 2026Review
- Hepatocyte nuclear factors dynamically regulate triglyceride metabolic reprogramming in metabolic dysfunction-associated steatotic liver disease: Mechanisms and implications.World journal of hepatology · 2025Review
- Bridging pancreatic and hepatic development: overlapping genes and their role in diabetes.Cellular & molecular biology letters · 2025Review
- Hepatocyte FoxO1 depletion exacerbates hepatic inflammation in MASH by targeting cystathionine γ-lyase.Scientific reports · 2025Article
- Identification of Glycolysis-Related Genes in MAFLD and Their Immune Infiltration Implications: A Multi-Omics Analysis with Experimental Validation.Biomedicines · 2025Article
- Pathogenesis and Clinical Management of Metabolic Dysfunction-Associated Steatotic Liver Disease.International journal of molecular sciences · 2025Review
- Insulin Resistance, Hyperinsulinemia and Atherosclerosis: Insights into Pathophysiological Aspects and Future Therapeutic Prospects.Current cardiology reviews · 2025Review
- Endoplasmic reticulum stress induces hepatic steatosis through interaction between PPARα and FoxO6 in vivo and in vitro.Journal of molecular medicine (Berlin, Germany) · 2024Article
- PANX1-mediated ATP release confers FAM3A's suppression effects on hepatic gluconeogenesis and lipogenesis.Military Medical Research · 2024Article
- Metabolic Dysfunction-Associated Steatotic Liver Disease: From Pathogenesis to Current Therapeutic Options.International journal of molecular sciences · 2024Review
- Article
- Vitamin D ameliorates age-induced nonalcoholic fatty liver disease by increasing the mitochondrial contact site and cristae organizing system (MICOS) 60 level.Experimental & molecular medicine · 2024Article
- lncRNA MSTRG4710 Promotes the Proliferation and Differentiation of Preadipocytes through miR-29b-3p/IGF1 Axis.International journal of molecular sciences · 2023Article
- Bariatric surgery improves postprandial VLDL kinetics and restores insulin-mediated regulation of hepatic VLDL production.JCI insight · 2023Article
- Pharmacotherapies of NAFLD: updated opportunities based on metabolic intervention.Nutrition & metabolism · 2023Review
86 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Excessive production of triglyceride-rich VLDL is attributable to hypertriglyceridemia. VLDL production is facilitated by microsomal triglyceride transfer protein (MTP) in a rate-limiting step that is regulated by insulin. To characterize the underlying mechanism, we studied hepatic MTP regulation by forkhead box O1 (FoxO1), a transcription factor that plays a key role in hepatic insulin signaling. In HepG2 cells, MTP expression was induced by FoxO1 and inhibited by exposure to insulin. This effect correlated with the ability of FoxO1 to bind and stimulate MTP promoter activity. Deletion or mutation of the FoxO1 target site within the MTP promoter disabled FoxO1 binding and resulted in abolition of insulin-dependent regulation of MTP expression. We generated mice that expressed a constitutively active FoxO1 transgene and found that increased FoxO1 activity was associated with enhanced MTP expression, augmented VLDL production, and elevated plasma triglyceride levels. In contrast, RNAi-mediated silencing of hepatic FoxO1 was associated with reduced MTP and VLDL production in adult mice. Furthermore, we found that hepatic FoxO1 abundance and MTP production were increased in mice with abnormal triglyceride metabolism. These data suggest that FoxO1 mediates insulin regulation of MTP production and that augmented MTP levels may be a causative factor for VLDL overproduction and hypertriglyceridemia in diabetes.
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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.