Distinct macrophage populations direct inflammatory versus physiological changes in adipose tissue

Area of Science:

• Immunology
• Metabolic Disease Research
• Cell Biology

Background:

• Obesity is linked to increased adipose tissue macrophages (ATMs), some forming crown-like structures (CLS).
• The functional diversity and underlying transcriptional mechanisms of different ATM subsets remain poorly understood.

Purpose of the Study:

• To delineate distinct ATM populations in obese adipose tissue.
• To characterize their unique tissue distributions, transcriptomes, chromatin landscapes, and functions.
• To investigate their roles in obesity pathogenesis in mice and humans.

Main Methods:

• Analysis of ATM populations in obese mouse and human adipose tissue.
• Transcriptomic and chromatin landscape profiling of ATM subsets.
• Adoptive transfer experiments of ATM subsets in mice.
• Comparative analysis of ATM populations between lean and obese states.

Main Results:

• Identified distinct mouse ATM subsets: Ly6c ATMs (outside CLS, adipogenic) and CD9 ATMs (within CLS, lipid-laden, proinflammatory).
• Adoptive transfer showed Ly6c ATMs promote adipocyte physiology, while CD9 ATMs drive obesity-associated gene expression.
• Human adipose tissue contains similar ATM populations, with CD9 ATMs increasing with body mass.

Conclusions:

• Obese adipose tissue harbors functionally heterogeneous ATM populations.
• Distinct ATM subsets play specific roles in adipose tissue inflammation and metabolic dysfunction.
• These findings offer a framework for developing targeted immunotherapies for obesity.