ArticleEndocrinology2014
FoxO6 integrates insulin signaling with MTP for regulating VLDL production in the liver.
Article in Endocrinology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 46 citations in OpenAlex.
- Expression of FOXO6 is Associated With Oxidative Stress Level and Predicts the Prognosis in Hepatocellular Cancer: A Comparative Study.Medicine · 2016Trial
- Liver-specific delivery of MDM2 antisense oligonucleotides counteracts diet-induced metabolic-dysfunction-associated steatotic liver diseases.Molecular therapy. Nucleic acids · 2026Article
- Disrupted renal clock and blood pressure rhythms in type 2 diabetic nephropathy.Clinical science (London, England : 1979) · 2026Article
- FOXO6 activation promotes hepatic steatosis via PPARα inhibition in aged male rats.BMB reports · 2026Article
- Metabolic Dysfunction-Associated Steatotic Liver Disease: From a Very Low-Density Lipoprotein Perspective.Biomolecules · 2025Review
- Targeting the FoxJ3/FoxO6 axis suppresses hepatocellular carcinoma growth by inducing cell cycle arrest and apoptosis.American journal of translational research · 2025Article
- Endoplasmic reticulum stress induces hepatic steatosis through interaction between PPARα and FoxO6 in vivo and in vitro.Journal of molecular medicine (Berlin, Germany) · 2024Article
- Article
- FoxO6-Mediated TXNIP Induces Lipid Accumulation in the Liver through NLRP3 Inflammasome Activation.Endocrinology and metabolism (Seoul, Korea) · 2024Article
- Article
- Important Hormones Regulating Lipid Metabolism.Molecules (Basel, Switzerland) · 2022Review
- Metabolic-associated fatty liver disease and lipoprotein metabolism.Molecular metabolism · 2021Review
- Mechanism of Lipid Accumulation through PAR2 Signaling in Diabetic Male Mice.Endocrinology and metabolism (Seoul, Korea) · 2021Article
- The association between SNPs rs1800591 and rs3816873 of the MTTP gene and nonalcoholic fatty liver disease: A meta-analysis.Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association · 2020Article
- Fatty liver diseases, mechanisms, and potential therapeutic plant medicines.Chinese journal of natural medicines · 2020Review
- Roux-en-Y Gastric Bypass in Obese Diabetic Rats Promotes Autophagy to Improve Lipid Metabolism through mTOR/p70S6K Signaling Pathway.Journal of diabetes research · 2020Article
- Article
- Knockdown of FOXO6 inhibits cell proliferation and ECM accumulation in glomerular mesangial cells cultured under high glucose condition.RSC advances · 2019Article
- Induction of Liver Steatosis in BAP31-Deficient Mice Burdened with Tunicamycin-Induced Endoplasmic Reticulum Stress.International journal of molecular sciences · 2018Article
- Elevated FOXO6 expression correlates with progression and prognosis in gastric cancer.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Excessive production of triglyceride-rich very low-density lipoproteins (VLDL-TG) contributes to hypertriglyceridemia in obesity and type 2 diabetes. To understand the underlying mechanism, we studied hepatic regulation of VLDL-TG production by (forkhead box O6) FoxO6, a forkhead transcription factor that integrates insulin signaling to hepatic metabolism. We showed that transgenic mice expressing a constitutively active FoxO6 allele developed hypertriglyceridemia, culminating in elevated VLDL-TG levels and impaired postprandial TG clearance. This effect resulted in part from increased hepatic VLDL-TG production. We recapitulated these findings in cultured HepG2 cells and human primary hepatocytes, demonstrating that FoxO6 promoted hepatic VLDL-TG secretion. This action correlated with the ability of FoxO6 to stimulate hepatic production of microsomal triglyceride transfer protein (MTP), a molecular chaperone that catalyzes the rate-limiting step in VLDL-TG assembly and secretion. FoxO6 was shown to bind to the MTP promoter and stimulate MTP promoter activity in HepG2 cells. This effect was inhibited by insulin, consistent with the ability of insulin to promote FoxO6 phosphorylation and disable FoxO6 DNA-binding activity. Mutations of the FoxO6 target site within the MTP promoter abrogated FoxO6-mediated induction of MTP promoter activity. Hepatic FoxO6 expression became deregulated in insulin-resistant mice with obesity and type 2 diabetes. FoxO6 inhibition in insulin-resistant liver suppressed hepatic MTP expression and curbed VLDL-TG overproduction, contributing to the amelioration of hypertriglyceridemia in obese and diabetic db/db mice. These results characterize FoxO6 as an important signaling molecule upstream of MTP for regulating hepatic VLDL-TG production.
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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.