TNF-α promotes insulin resistance in obstructive sleep apnea-hypopnea syndrome

Lin Zhao1, Yang Liu1, Xiangrong Wang2

  • 1Department of Endocrinology, The 8th Medical Center of Chinese People's Liberation Army General Hospital, Beijing 100091, P.R. China.

Insights

Tumor necrosis factor-alpha (TNF-α) in obstructive sleep apnea hypopnea syndrome (OSAHS) reduces glucose transporter type 4 insulin-responsive (GLUT-4) expression, promoting insulin resistance via the TNF-α/IKKβ/IKβ/NF-κB pathway.

Area of Science:

  • Pediatric Endocrinology
  • Sleep Medicine
  • Molecular Biology

Background:

  • Obstructive sleep apnea hypopnea syndrome (OSAHS) is a severe sleep-disordered breathing condition in children.
  • Insulin resistance is a growing concern in obese children with OSAHS.
  • The molecular mechanisms linking OSAHS to insulin resistance require further elucidation.

Purpose of the Study:

  • To investigate the role of tumor necrosis factor-alpha (TNF-α) in modulating glucose transporter type 4 insulin-responsive (GLUT-4) expression.
  • To determine if TNF-α promotes insulin resistance through the TNF-α/IKKβ/IKβ/NF-κB signaling pathway in pediatric OSAHS.
  • To compare molecular markers between obese children with and without OSAHS.

Main Methods:

  • Western blot analysis and immunohistochemistry were used to detect protein expression in adenoid tissues.
  • Quantified TNF-α, inflammatory factors (IL-1β, IL-6, IFN-γ), and signaling pathway proteins (IKKβ, IKβ, NF-κB).
  • Assessed expression of insulin resistance markers, including insulin receptor substrate 1 (IRS1) and GLUT-4.

Main Results:

  • Elevated TNF-α expression was observed in adenoid tissues of children with OSAHS.
  • Increased levels of inflammatory factors (IL-1β, IL-6, IFN-γ) and activated TNF-α/IKKβ/IKβ/NF-κB pathway were found in OSAHS.
  • Reduced expression of IRS1 and GLUT-4, indicative of insulin resistance, was associated with OSAHS.

Conclusions:

  • TNF-α expression is upregulated in pediatric OSAHS.
  • The TNF-α/IKKβ/IKβ/NF-κB pathway is activated in children with OSAHS.
  • TNF-α suppresses GLUT-4 expression, contributing to insulin resistance in OSAHS through this signaling pathway.

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