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Updated: Feb 22, 2026
Isolation, Characterization, and Purification of Macrophages from Tissues Affected by Obesity-related Inflammation
Published on: April 3, 2017
Metabolically Activated Adipose Tissue Macrophages Perform Detrimental and Beneficial Functions during Diet-Induced
Brittney R Coats1, Kelly Q Schoenfelt2, Valéria C Barbosa-Lorenzi3
1Committee on Molecular Metabolism and Nutrition, The University of Chicago, Chicago, IL 60637, USA.
Abstract:
During obesity, adipose tissue macrophages (ATMs) adopt a metabolically activated (MMe) phenotype. However, the functions of MMe macrophages are poorly understood. Here, we combine proteomic and functional methods to demonstrate that, in addition to potentiating inflammation, MMe macrophages promote dead adipocyte clearance through lysosomal exocytosis. We identify NADPH oxidase 2 (NOX2) as a driver of the inflammatory and adipocyte-clearing properties of MMe macrophages and show that, compared to wild-type, Nox2-/- mice exhibit a time-dependent metabolic phenotype during diet-induced obesity. After 8 weeks of high-fat feeding, Nox2-/- mice exhibit attenuated ATM inflammation and mildly improved glucose tolerance. After 16 weeks of high-fat feeding, Nox2-/- mice develop severe insulin resistance, hepatosteatosis, and visceral lipoatrophy characterized by dead adipocyte accumulation and defective ATM lysosomal exocytosis, a phenotype reproduced in myeloid cell-specific Nox2-/- mice. Collectively, our findings suggest that MMe macrophages perform detrimental and beneficial functions whose contribution to metabolic phenotypes during obesity is determined by disease progression.
Insights
Metabolically activated macrophages in obesity clear dead fat cells via lysosomal exocytosis. The enzyme NADPH oxidase 2 (NOX2) drives this process, but its absence worsens obesity-related metabolic dysfunction over time.
Area of Science:
- Immunology
- Metabolic Diseases
- Cell Biology
Background:
- Obesity leads to adipose tissue macrophages (ATMs) adopting a metabolically activated (MMe) phenotype.
- The precise functions of MMe macrophages in obesity are not fully understood.
Purpose of the Study:
- To investigate the functions of MMe macrophages in obesity.
- To identify key molecular drivers of MMe macrophage functions.
- To determine the role of NADPH oxidase 2 (NOX2) in obesity-related metabolic changes.
Main Methods:
- Proteomic and functional analyses of ATMs.
- Studies using wild-type and Nox2 knockout (Nox2-/-) mice fed a high-fat diet.
- Assessment of metabolic parameters, inflammation, and adipocyte clearance.
Main Results:
- MMe macrophages clear dead adipocytes via lysosomal exocytosis and potentiate inflammation.
- NADPH oxidase 2 (NOX2) drives both the inflammatory and adipocyte-clearing functions of MMe macrophages.
- Nox2-/- mice show improved glucose tolerance early in diet-induced obesity but develop severe insulin resistance, hepatosteatosis, and lipoatrophy later, with impaired dead adipocyte clearance.
Conclusions:
- MMe macrophages have dual roles in obesity, promoting inflammation and clearing dead adipocytes.
- NOX2 is crucial for MMe macrophage functions, with its absence leading to detrimental metabolic outcomes as obesity progresses.
- The contribution of MMe macrophage functions to metabolic phenotypes is dependent on the stage of obesity.
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