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Cited by 195

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Targeting Forkhead Box O1 from the Concept to Metabolic Diseases: Lessons from Mouse Models

Open access
Cheng, Zhiyong, White, Morris F.·2011·Antioxidants & Redox Signaling

Abstract

Forkhead box O (FOXO) transcription factors have been implicated in regulating the metabolism, cellular proliferation, stress resistance, apoptosis, and longevity. Through the insulin receptor substrate → phosphoinositide 3-kinase → Akt signal cascade, FOXO integrates insulin action with the systemic nutrient and energy homeostasis. Activation of FOXO1 in liver induces gluconeogenesis via phosphoenolpyruvate carboxykinase (PEPCK)/glucose 6-phosphate pathway, and disrupts mitochondrial metabolism and lipid metabolism via heme oxygenase 1/sirtuin 1/Ppargc1α pathway. In skeletal muscle, FOXO1 activation underpins the carbohydrate/lipid switch during fasting state. Inhibition of FOXO1 under physiological conditions accounts for maintenance of skeletal muscle mass/function and adipose differentiation. In pancreatic β-cells, nuclear translocation of FOXO1 antagonizes pancreatic and duodenal homeobox 1 and attenuates β-cells proliferation and insulin secretion. Regardless, FOXO1 promotes the proliferation of β-cells through induction of Cyclin D1 in low nutrition, and elicits antioxidant mechanism to protect against β-cell failure during oxidative insults. In the brain, FOXO1 controls food intake through transcriptional regulation of the orexigenic neuropeptide Y, agouti-related protein, and carboxypeptidase E. In this article, we review the role of FOXO1 in the regulation of metabolism and energy expenditure based on recent findings from mouse models, and discuss the therapeutic value of targeting FOXO1 in metabolic diseases.

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Metadata

Authors
Cheng, Z., & White, M. F.
Venue
Antioxidants & Redox Signaling
Published
2011-02-15
Volume
14
Issue
4
Pages
649-661
ISSN
  • 1523-0864 (ISSN-L)
  • 1557-7716
OpenAlex
W1965818907
Cited by
195
References
21
FWCI
6.85
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: Targeting Forkhead Box O1 from the Concept to Metabolic Diseases: Lessons from Mouse Models. https://app.cochat.ai/papers/10.1089/ars.2010.3370
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Cheng, Z., & White, M. F. (2011). Targeting Forkhead Box O1 from the Concept to Metabolic Diseases: Lessons from Mouse Models. Antioxidants & Redox Signaling. https://doi.org/10.1089/ars.2010.3370

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