Macrophage glucose-6-phosphate dehydrogenase stimulates proinflammatory responses with oxidative stress

Area of Science:

• Biochemistry
• Immunology
• Metabolic Research

Background:

• Glucose-6-phosphate dehydrogenase (G6PD) is crucial for cellular redox balance.
• Obesity is linked to chronic inflammation and oxidative stress in adipose tissue.
• The role of macrophage G6PD in obesity-related inflammation is not fully understood.

Purpose of the Study:

• To investigate the role of macrophage G6PD in modulating inflammatory responses and oxidative stress in obese adipose tissue.
• To explore the molecular mechanisms linking macrophage G6PD to inflammation and insulin resistance.

Main Methods:

• Assessed G6PD levels in adipose tissue macrophages of obese animals.
• Stimulated macrophages with lipopolysaccharide (LPS) and free fatty acids.
• Utilized chemical inhibitors and small interfering RNA (siRNA) to suppress macrophage G6PD.
• Measured gene expression of proinflammatory and oxidative stress markers.
• Analyzed activation of p38 MAPK and NF-κB signaling pathways.

Main Results:

• Elevated macrophage G6PD levels in obese animals correlated with increased proinflammatory gene expression.
• LPS and free fatty acids stimulated macrophage G6PD activity.
• Overexpression of macrophage G6PD exacerbated proinflammatory and pro-oxidative gene expression, worsening insulin sensitivity.
• Inhibition or suppression of macrophage G6PD attenuated both basal and LPS-induced inflammation.
• Macrophage G6PD enhanced p38 MAPK and NF-κB pathway activation.

Conclusions:

• Abnormal elevation of G6PD in macrophages promotes oxidative stress and inflammation in obese adipose tissue.
• Macrophage G6PD contributes to a cycle of oxidative stress and inflammation, impacting insulin sensitivity.
• Targeting macrophage G6PD may represent a novel therapeutic strategy for obesity-related metabolic dysfunction.