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- Title
Macrophage immunophenotype but not anti-inflammatory profile is modulated by peroxisome proliferator-activated receptor gamma (PPARγ) in exercised obese mice.
- Authors
Sanches Silveira, Loreana; Amorim Biondo, Luana; de Souza Teixeira, Alexandre Abílio; Alves de Lima Junior, Edson; Castoldi, Angela; Saraiva Câmara, Niels Olsen; Festuccia, Willian T.; Rosa-Neto, José Cesar; Santos Lira, Fábio
- Abstract
Moderate aerobic training may be therapeutic for chronic low-grade inflammatory diseases due to the associated antiinflammatory response that is mediated by immune cells. The peroxisome proliferator-activated receptor gamma (PPARγ) regulates the Ml (pro-inflammatory) and M2 (anti-inflammatory) polarization, as well as the immunometabolic response of macrophages. Against this background, the present study seeks to clarify whether the conditional deletion of PPARγ in macrophages would have any effect on the anti-inflammatory role of moderate aerobic training. To test this hypothesis, two mice strains were used: PPARγ LyzCre+/+ (KO) and litter-mates control animals (WT). Each genotype was divided into 1) sedentary high-fat diet (HF) and 2) high-fat diet and moderate aerobic training (HFT) (n = 5-8 per group). The experimental protocol lasted for 12 weeks, comprising 4 weeks of HF diet only and 8 weeks of HF diet and aerobic training (5 times/week, 50-60 minutes/day at 60% of maximum speed). Metabolic analyses were carried out on the serum glucose homeostase, adipose tissue morphology and cytokine content, and macrophage cytokine production. Immunophenotyping and gene expression were also performed. KO male mice were more prone to hypertrophy in the subcutaneous adipose tissue, though only the IL-1β (p = 0.0049) was higher compared to the values observed in WT animals. Peritoneal macrophages from KO animals exhibited a marked inflammatory environment with an increase in TNF-α (p = 0.0008), IL- 1β (p = 0.0017), and IL-6 (p < 0.0001) after lipopolysaccharide stimulation. The moderate aerobic training protected both genotypes from weight gain and reduced the caloric intake in the KO animals. Despite the attenuation of the M2 marker CD206 (p < 0.001) in the absence of PPAR-γ, the aerobic training modulated cytokine production in LPS stimulated peritoneal macrophages from both genotypes, reducing proinflammatory cytokines such as TNF-α (p = 0.0002) and IL-6 (p < 0.0001). Overall, our findings demonstrate the essential role of PPARγ in macrophage immunophenotypes. However, the deletion of PPARγ did not inhibit the exercise-mediated anti-inflammatory effect, underscoring the important role of exercise in modulating inflammation.
- Subjects
PEROXISOME proliferator-activated receptors; AEROBIC exercises; PERITONEAL macrophages; MACROPHAGES; WEIGHT gain
- Publication
Exercise Immunology Review, 2020, Vol 26, p94
- ISSN
1077-5552
- Publication type
Article