Macrophage Phenotypic Switch and Obesity-Associated Metabolic Risk: Mechanisms and Targets

Area of Science:

• Immunology
• Metabolic Health
• Adipose Tissue Biology

Background:

• Obesity is linked to chronic inflammation (metaflammation) driven by adipose tissue (AT) dysfunction.
• Macrophages are key immune cells regulating AT homeostasis and inflammation.

Purpose of the Study:

• To review macrophage polarization in obesity.
• To highlight ATM plasticity, heterogeneity, and interactions.
• To discuss regulatory factors and emerging macrophage subsets in AT inflammation.

Main Methods:

• Literature review of macrophage polarization in obesity.
• Analysis of transcriptomic plasticity and functional heterogeneity of ATMs.
• Examination of regulatory transcription factors (HIF-1α, PPARγ) and macrophage subsets (CD9+, Trem2+ LAMs).

Main Results:

• Obesity induces ATM phenotypic switch to a pro-inflammatory M1 profile.
• Crown-like structures (CLSs) are hallmarks of AT inflammation.
• Transcription factors like HIF-1α and PPARγ regulate macrophage polarization.
• Lipid-associated macrophages (LAMs) play dual roles in AT remodeling and inflammation.

Conclusions:

• Understanding macrophage activation in obese AT is crucial for therapeutic development.
• Targeting macrophage polarization may mitigate metabolic risks associated with obesity.
• Restoring AT function requires addressing macrophage-driven inflammation.