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Effect of high fat diet on NF-кB microRNA146a negative feedback loop in ovalbumin-sensitized rats
Godrat Akhavanakbari1, Behzad Babapour2, Mohammad Reza Alipour3
1Department of Anesthesiology, Faculty of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran.
Abstract:
The present study aimed to investigate the role of microRNA-146a and its adapter proteins [interleukin-1 receptor-associated kinase 1 (IRAK1) and tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6)] in the pathogenesis of ovalbumin (OVA)-sensitized rats in association with the diet-induced obesity condition. Twenty male Wistar rats were divided into four groups: control with normal diet (ND), OVA-sensitized with normal diet (S + ND), high-fat diet (HFD), and OVA-sensitized with high-fat diet (S + HFD). All the animals were fed for 8 weeks with standard pelts or high-fat diet, and were then sensitized and challenged with OVA or saline for another 4 weeks. The tracheal responsiveness to methacholine, serum protein levels, and lipid profile levels was measured by the ELISA method. Moreover, the gene expression level of microRNA-146a (miR-146a) was measured in the lung tissue of the rats using the real-time PCR method. Maximum response to methacholin increased in the S + HFD group in compared with ND, S + ND, and HFD groups (P < 0.05 to P < 0.001). Moreover, in the S + HFD group the mRNA expression levels of miRNA-146a increased in the lung tissue (P < 0.001). In addition, the protein analysis results showed that IRAK1, TRAF6, NF-kB, and IL-1β protein levels were high in the S + HFD group compared to the ND and HFD groups; however, in compared with the S + ND group, only the IL-1β protein level was higher in the S + HFD group (P < 0.05). These results suggest that a defect in the NF-kB-miR-146a negative feedback loop may be involved in the pathogenesis of obesity associated with OVA-sensitized condition. © 2018 BioFactors, 45(1):75-84, 2019.
Insights
Diet-induced obesity exacerbates ovalbumin sensitization in rats, increasing microRNA-146a and inflammatory markers. A defective NF-kB-miR-146a feedback loop may drive this obesity-associated pathogenesis.
Area of Science:
- Immunology and Inflammation
- Metabolic Disorders
- Molecular Biology
Background:
- Obesity is a growing health concern, and its interaction with allergic sensitization is not fully understood.
- MicroRNA-146a (miR-146a) plays a role in immune regulation, but its involvement in obesity-associated allergic conditions requires further investigation.
- Adapter proteins like IRAK1 and TRAF6 are key components of inflammatory signaling pathways.
Purpose of the Study:
- To investigate the role of miR-146a and its associated proteins (IRAK1, TRAF6) in rats sensitized to ovalbumin (OVA) and fed a high-fat diet (HFD).
- To explore the impact of diet-induced obesity on airway hyperresponsiveness and inflammatory markers in OVA-sensitized rats.
- To examine the potential involvement of the NF-kB-miR-146a feedback loop in the pathogenesis of this condition.
Main Methods:
- Wistar rats were divided into four groups: control (normal diet), OVA-sensitized (normal diet), high-fat diet, and OVA-sensitized (high-fat diet).
- Animals were fed for 8 weeks, followed by 4 weeks of sensitization/challenge with OVA or saline.
- Measurements included tracheal responsiveness to methacholine, serum protein and lipid profiles (ELISA), and lung miR-146a gene expression (real-time PCR).
Main Results:
- OVA-sensitized rats on a high-fat diet (S + HFD) exhibited significantly increased tracheal responsiveness to methacholine compared to all other groups.
- The S + HFD group showed elevated mRNA expression levels of miR-146a in lung tissue.
- Protein analysis revealed higher levels of IRAK1, TRAF6, NF-kB, and IL-1β in the S + HFD group compared to control and HFD groups, with significantly higher IL-1β compared to the S + ND group.
Conclusions:
- Diet-induced obesity exacerbates allergic airway inflammation in OVA-sensitized rats, leading to increased airway hyperresponsiveness and elevated inflammatory markers.
- The study suggests a potential defect in the NF-kB-miR-146a negative feedback loop contributes to the pathogenesis of obesity associated with OVA sensitization.
- These findings highlight the complex interplay between metabolic status and immune responses in allergic diseases.
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