4E-BP-Dependent Translational Control of Irf8 Mediates Adipose Tissue Macrophage Inflammatory Response

Area of Science:

• Molecular Biology
• Immunology
• Metabolic Diseases

Background:

• Deregulation of mRNA translation is linked to various human disorders, including obesity and cancer.
• The role of eukaryotic initiation factor 4E (eIF4E)-dependent translational control in macrophage inflammation in vivo remains largely uncharacterized.

Purpose of the Study:

• To investigate the involvement of translation inhibitors, 4E-binding proteins (4E-BPs), in regulating macrophage inflammatory responses.
• To elucidate the role of the 4E-BP-IRF8 axis in adipose tissue inflammation during high-fat diet (HFD) exposure.

Main Methods:

• Utilized bone marrow-derived macrophages and adipose tissue macrophages from wild-type and 4E-BP-null mice.
• Administered a high-fat diet (HFD) to assess inflammatory responses and gene expression.
• Quantified mRNA translation of Irf8 and IRF8 protein expression.

Main Results:

• Absence of 4E-BPs exacerbated inflammatory polarization of macrophages.
• 4E-BP-null adipose tissue macrophages showed enhanced inflammatory gene expression upon HFD exposure.
• HFD-fed 4E-BP-null mice exhibited increased weight gain, higher Irf8 mRNA translation, and elevated IRF8 expression.

Conclusions:

• 4E-binding proteins limit the proinflammatory response in adipose tissue macrophages during high-fat diets.
• The 4E-BP-IRF8 axis is a critical regulatory mechanism controlling proinflammatory responses in adipose tissue macrophages, impacting metabolic health.