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Macrophage-specific PPARgamma controls alternative activation and improves insulin resistance
Justin I Odegaard1, Roberto R Ricardo-Gonzalez, Matthew H Goforth
1Division of Endocrinology, Metabolism and Gerontology, Department of Medicine, Stanford University School of Medicine, Stanford, California 94305-5103, USA.
Nature
|May 23, 2007
Summary
Resident alternatively activated macrophages, crucial for tissue repair, play a beneficial role in preventing obesity-induced insulin resistance. Targeting macrophage polarization may offer a new strategy for treating type 2 diabetes.
Area of Science:
- Metabolic Syndrome and Inflammation
- Immunology and Metabolism
Background:
- Obesity and insulin resistance, hallmarks of metabolic syndrome, are linked to chronic low-grade inflammation.
- Adipose tissue inflammation, driven by macrophage infiltration, exacerbates insulin resistance.
- While pro-inflammatory macrophages are well-studied, the role of alternatively activated macrophages in metabolic health is unclear.
Purpose of the Study:
- To investigate the role of alternatively activated macrophages in diet-induced obesity and insulin resistance.
- To determine the necessity of peroxisome proliferator-activated receptor-gamma (PPARgamma) in alternative macrophage activation and its impact on metabolic homeostasis.
Main Methods:
- Utilized mice with macrophage-specific deletion of PPARgamma.
- Analyzed macrophage infiltration, adipose tissue inflammation, insulin sensitivity, and glucose tolerance.
- Performed gene expression profiling of skeletal muscle and liver.
Main Results:
- Macrophage-specific PPARgamma deletion impaired alternative macrophage activation.
- These mice exhibited increased susceptibility to diet-induced obesity, insulin resistance, and glucose intolerance.
- Downregulation of oxidative phosphorylation gene expression in liver and muscle correlated with decreased insulin sensitivity.
Conclusions:
- Alternatively activated macrophages, dependent on PPARgamma, play a protective role in regulating nutrient homeostasis.
- Impaired alternative macrophage polarization contributes to obesity-induced insulin resistance.
- Promoting macrophage polarization towards the alternative state could be a therapeutic strategy for type 2 diabetes.
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