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FoxO integration of insulin signaling with glucose and lipid metabolism

Sojin Lee1, H Henry Dong2

  • 1Division of Endocrinology and DiabetesDepartment of Pediatrics, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

The Journal of Endocrinology
|February 19, 2017
PubMed

Insights

Forkhead box O6 (FoxO6) plays a unique role in regulating metabolism and brain function, distinct from other FoxO proteins. Understanding FoxO6 is crucial for addressing diabetes and neurodegenerative diseases.

Area of Science:

  • Molecular Biology
  • Endocrinology
  • Neuroscience

Background:

  • The forkhead box O (FoxO) family comprises four mammalian proteins (FoxO1, FoxO3, FoxO4, FoxO6) involved in crucial cellular functions.
  • FoxO proteins regulate insulin/IGF signaling impacting metabolism, growth, differentiation, oxidative stress, senescence, autophagy, and aging.
  • Altered FoxO expression is linked to metabolic diseases, cancer, and lifespan alterations.

Purpose of the Study:

  • To review the distinct role of FoxO6, compared to other FoxO isoforms, in health and disease.
  • To elucidate the unique mechanism of FoxO6 in integrating insulin signaling with hepatic glucose and lipid metabolism.
  • To highlight FoxO6's involvement in neurodegeneration, aging, and its potential as a therapeutic target.

Main Methods:

  • Literature review focusing on FoxO6 function and its contrast with other FoxO isoforms.
  • Analysis of FoxO6's role in insulin signaling pathways.
  • Examination of FoxO6's contribution to metabolic and neurological conditions.

Main Results:

  • FoxO6 exhibits an evolutionarily divergent mechanism in mediating insulin action compared to other FoxO members.
  • Dysregulation of FoxO6 is implicated in the pathogenesis of insulin resistance, obesity, type 2 diabetes, hyperglycemia, and hyperlipidemia.
  • FoxO6 is involved in memory consolidation and contributes to neurodegeneration and aging.

Conclusions:

  • FoxO6 plays a pivotal, yet understudied, role in liver, skeletal muscle, and brain functions.
  • FoxO6 dysregulation contributes significantly to metabolic disorders like diabetes and neurodegenerative diseases.
  • Pharmacological inhibition of FoxO6 presents a potential therapeutic strategy for managing glucose and lipid metabolism in diabetes.
Keywords:
FoxO1FoxO3FoxO4FoxO6diabetesglucose metabolisminsulin signalinglipid metabolismobesity

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