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Citations to this article

Foxo1 mediates insulin action on apoC-III and triglyceride metabolism
Jennifer Altomonte, … , Marcia Meseck, Hengjiang Henry Dong
Jennifer Altomonte, … , Marcia Meseck, Hengjiang Henry Dong
Published November 15, 2004
Citation Information: J Clin Invest. 2004;114(10):1493-1503. https://doi.org/10.1172/JCI19992.
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Article Metabolism Article has an altmetric score of 11

Foxo1 mediates insulin action on apoC-III and triglyceride metabolism

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Abstract

The apolipoprotein apoC-III plays an important role in plasma triglyceride metabolism. It is predominantly produced in liver, and its hepatic expression is inhibited by insulin. To elucidate the inhibitory mechanism of insulin in apoC-III expression, we delivered forkhead box O1 (Foxo1) cDNA to hepatocytes by adenovirus-mediated gene transfer. Foxo1 stimulated hepatic apoC-III expression and correlated with the ability of Foxo1 to bind to its consensus site in the apoC-III promoter. Deletion or mutation of the Foxo1 binding site abolished insulin response and Foxo1-mediated stimulation. Likewise, Foxo1 also mediated insulin action on intestinal apoC-III expression in enterocytes. Furthermore, elevated Foxo1 production in liver augmented hepatic apoC-III expression, resulting in increased plasma triglyceride levels and impaired fat tolerance in mice. Transgenic mice expressing a constitutively active Foxo1 allele exhibited hypertriglyceridemia. Moreover, we show that hepatic Foxo1 expression becomes deregulated as a result of insulin deficiency or insulin resistance, culminating in significantly elevated Foxo1 production, along with its skewed nuclear distribution, in livers of diabetic NOD or db/db mice. While loss of insulin response is associated with unrestrained apoC-III production and impaired triglyceride metabolism, these data suggest that Foxo1 provides a molecular link between insulin deficiency or resistance and aberrant apoC-III production in the pathogenesis of diabetic hypertriglyceridemia.

Authors

Jennifer Altomonte, Lin Cong, Sonal Harbaran, Anja Richter, Jing Xu, Marcia Meseck, Hengjiang Henry Dong

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Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 Total
Citations: 1 7 9 7 9 10 9 4 10 5 9 4 8 9 10 7 5 7 3 6 1 140
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Citations to this article in year 2023 (9)

Title and authors Publication Year
APOC-III: a Gatekeeper in Controlling Triglyceride Metabolism
Giammanco A, Spina R, Cefalù AB, Averna M
Current Atherosclerosis Reports 2023
Regulation of Liver Glucose and Lipid Metabolism by Transcriptional Factors and Coactivators
Ramatchandirin B, Pearah A, He L
Life Sciences 2023
FOXO4-D-Retro-Inverso targets extracellular matrix production in fibroblasts and ameliorates bleomycin-induced pulmonary fibrosis in mice.
Liu Y, Hou Q, Wang R, Liu Y, Cheng Z
Naunyn-Schmiedeberg's Archives of Pharmacology 2023
Quartet of APOCs and the Different Roles They Play in Diabetes.
Hsu CC, Kanter JE, Kothari V, Bornfeldt KE
Arteriosclerosis, thrombosis, and vascular biology 2023
FOXO transcription factors as mediators of stress adaptation.
Rodriguez-Colman MJ, Dansen TB, Burgering BMT
Nature reviews. Molecular cell biology 2023
FoxO1 as a tissue-specific therapeutic target for type 2 diabetes
Teaney NA, Cyr NE
Frontiers in Endocrinology 2023
Acne Transcriptomics: Fundamentals of Acne Pathogenesis and Isotretinoin Treatment
Melnik BC
Cells 2023
Insulin Regulation of Hepatic Lipid Homeostasis
Uehara K, Santoleri D, Whitlock AE, Titchenell PM
Comprehensive Physiology 2023
Molecular profiling of high-level athlete skeletal muscle after acute endurance or resistance exercise – A systems biology approach
Reitzner SM, Emanuelsson EB, Arif M, Kaczkowski B, Kwon AT, Mardinoglu A, Arner E, Chapman MA, Sundberg CJ
Molecular Metabolism 2023

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