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Differentiated Mouse Adipocytes in Primary Culture: A Model of Insulin Resistance
Published on: February 17, 2023
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.
Abstract:
Obstructive sleep apnea hypopnea syndrome (OSAHS) is the most serious among children with sleep disordered breathing. The present study aimed to investigate whether TNF-α could decrease the glucose transporter type 4 insulin-responsive (GLUT-4) expression to promote insulin resistance through the TNF-α/IKKβ/IKβ/NF-κB signaling pathway in OSAHS. In total, 30 obese children with OSAHS and 30 non-OSAHS obese children were enrolled into the present study. TNF-α expression in adenoid tissues was detected by western blot analysis and immunohistochemistry. The expression of inflammatory factors (IL-1β, IL-6 and IFN-γ) and TNF-α/IKKβ/IKβ/NF-κB signaling pathway-associated proteins was also detected by western blot analysis. The expression of insulin resistance-associated factors, insulin receptor substrate 1 (IRS1) and GLUT4, was determined by western blot analysis and immunohistochemistry. TNF-α expression was increased in adenoid tissues of children with OSAHS, which was also confirmed by immunohistochemistry. The expression levels of IL-1β, IL-6 and IFN-γ were all upregulated in adenoid tissues of children with OSAHS. The expression of IRS1 and GLUT4 was decreased in adenoid tissues of obese children with OSAHS and the result of immunohistochemistry was consistent with the result of western blot analysis. The protein level of TNF-α, and ratio of phosphorylated (p-)/total (t)-IKKβ, p/t-IKβ and p/t-NF-κB was increased in adenoid tissues of children with OSAHS. TNF-α could suppress the GLUT4 expression to promote insulin resistance by TNF-α/IKKβ/IKβ/NF-κB signaling pathway in OSAHS.
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