Microglia Mediate Metabolic Dysfunction From Common Air Pollutants Through NF-κB Signaling.

Area of Science:

• Environmental Health
• Metabolic Diseases
• Neuroimmunology

Background:

• Type 2 diabetes (T2D) prevalence is a global health concern.
• The role of air pollutants, like volatile organic compounds (VOCs), in T2D is under-researched.
• Benzene, a common airborne VOC, has been correlated with T2D.

Purpose of the Study:

• To conduct the first meta-analysis on benzene exposure and insulin resistance.
• To investigate the mechanisms linking benzene exposure to metabolic dysfunction in mice.
• To identify the role of microglial signaling in benzene-induced metabolic disturbances.

Main Methods:

• Meta-analysis of human studies on benzene exposure and T2D.
• Controlled benzene exposure, continuous glucose monitoring, and indirect calorimetry in mice.
• RNA sequencing of microglia and selective gene ablation studies in mice.

Main Results:

• A robust association between benzene exposure and insulin resistance was established.
• Benzene exposure in male mice disrupted energy homeostasis and hypothalamic gene expression.
• Microglial NF-κB pathway activation was identified as a key mediator of benzene-induced metabolic dysfunction.
• Targeted ablation of IKKβ in immune cells or microglia protected against hyperglycemia.

Conclusions:

• Benzene exposure is linked to insulin resistance and metabolic disturbances.
• The microglial NF-κB pathway is critical in mediating chemical-induced metabolic diseases.
• This study reveals a pathophysiological mechanism connecting airborne toxicants to metabolic disease onset.