ArticleEndocrinology2012
Hepatic suppression of Foxo1 and Foxo3 causes hypoglycemia and hyperlipidemia in mice.
Article in Endocrinology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
105 citing papers in PubMed, 1 synthesis or guideline pooled it, 177 citations in OpenAlex.
- Evaluating the roles of microRNAs associated with nonalcoholic fatty liver disease in hepatocellular carcinoma tumorigenesis: a systematic review and network analysis.Frontiers in medicine · 2024Pooled it
- Trial
- Paternal folate deficiency induces hepatic insulin resistance in offspring mice.Nutrition & diabetes · 2026Article
- Transcriptomic and epigenetic alterations in aging-related genes in the medaka liver due to ancestral BPA exposure.Journal of the Endocrine Society · 2026Article
- Hepatic Glucocorticoid Receptor Action and Glucose Homeostasis.Endocrine reviews · 2026Review
- FOXO: a key target in regulating aging and age-related diseases.Biogerontology · 2026Review
- Studies of Foxo1 over the Past 25 Years: Mechanisms of Insulin Resistance and Glucose Dysregulation.Cells · 2026Review
- Methotrexate alleviates chronic inflammation in a Drosophila model.Journal of cell science · 2025Article
- Single-cell eQTL analysis identifies genetic variation underlying metabolic dysfunction-associated steatohepatitis.Nature genetics · 2025Article
- Coordinated Regulation of Renal Glucose Reabsorption and Gluconeogenesis by mTORC2 and Potassium.Journal of the American Society of Nephrology : JASN · 2025Article
- The Protective Effect of FOXO3 rs2802292 G-Allele on Food Intake in a Southern Italian Cohort Affected by MASLD.Nutrients · 2025Article
- Dnmt3a-mediated hypermethylation of FoxO3 promotes redox imbalance during osteoclastogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Pathogenetic therapeutic approaches for endocrine diseases based on antisense oligonucleotides and RNA-interference.Frontiers in endocrinology · 2025Review
- Antidiabetic and Antihyperlipidemic Activities and Molecular Mechanisms ofCurrent issues in molecular biology · 2024Article
- An estrogen receptor α-derived peptide improves glucose homeostasis during obesity.Nature communications · 2024Article
- Mechanisms underlying retardation of aging by dietary energy restriction.Pathology international · 2023Review
- Regulation of Macronutrients in Insulin Resistance and Glucose Homeostasis during Type 2 Diabetes Mellitus.Nutrients · 2023Review
- Normobaric hypoxia shows enhanced FOXO1 signaling in obese mouse gastrocnemius muscle linked to metabolism and muscle structure and neuromuscular innervation.Pflugers Archiv : European journal of physiology · 2023Article
- Suppression of FOXO1 attenuates inflamm-aging and improves liver function during aging.Aging cell · 2023Article
- Transcription Factor Forkhead Box O1 Mediates Transforming Growth Factor-β1-Induced Apoptosis in Hepatocytes.The American journal of pathology · 2023Article
45 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Dysregulation of blood glucose and triglycerides are the major characteristics of type 2 diabetes mellitus. We sought to identify the mechanisms regulating blood glucose and lipid homeostasis. Cell-based studies established that the Foxo forkhead transcription factors Forkhead box O (Foxo)-1, Foxo3, and Foxo4 are inactivated by insulin via a phosphatidylinositol 3-kinase/Akt-dependent pathway, but the role of Foxo transcription factors in the liver in regulating nutrient metabolism is incompletely understood. In this study, we used the Cre/LoxP genetic approach to delete the Foxo1, Foxo3, and Foxo4 genes individually or a combination of two or all in the liver of lean or db/db mice and assessed the role of Foxo inactivation in regulating glucose and lipid homeostasis in vivo. In the lean mice or db/db mice, hepatic deletion of Foxo1, rather than Foxo3 or Foxo4, caused a modest reduction in blood glucose concentrations and barely affected lipid homeostasis. Combined deletion of Foxo1 and Foxo3 decreased blood glucose levels, elevated serum triglyceride and cholesterol concentrations, and increased hepatic lipid secretion and caused hepatosteatosis. Analysis of the liver transcripts established a prominent role of Foxo1 in regulating gene expression of gluconeogenic enzymes and Foxo3 in the expression of lipogenic enzymes. Our findings indicate that Foxo1 and Foxo3 inactivation serves as a potential mechanism by which insulin reduces hepatic glucose production and increases hepatic lipid synthesis and secretion in healthy and diabetic states.
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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.