Evaluation of the immuno-metabolic response in peritonal macrophages of obese mice: role of physical exercise and PPAR-γ

Author(s)

Loreana Sanches Silveira

• Document type: Doctoral Thesis
• Press: Presidente Prudente. 2019-01-21.
• Institution: Universidade Estadual Paulista (Unesp). Faculdade de Ciências e Tecnologia. Presidente Prudente
• Defense date: 2018-12-11
• Advisor: Fábio Santos de Lira

Abstract

Aerobic physical training is considered a therapy for chronic low-grade inflammatory diseases due to its anti-inflammatory response mediated by immune cells. The peroxisome proliferator-activated receptor gamma (PPAR-γ) is able to regulate the M1 (pro-inflammatory) and M2 (anti-inflammatory) polarization, as well as the immunometabolic response of macrophages. Thus, we propose in the present thesis to verify whether the conditional deletion of PPAR-γ in macrophages would have any effect on the anti-inflammatory role of moderate aerobic exercise. To test our hypothesis, two animal strains were used: PPAR-γ LyzCre+/+ (KO) and littermates control animals (WT). Each genotype was divided into 1) sedentary control diet; 2) control diet and moderate training (T); 3) sedentary high fat diet (HF) and 4) high fat diet and moderate training (HFT). The experimental protocol lasted for 12 weeks, four weeks of diet only and eight weeks of diet and exercise. The metabolic profile of the animals and the inflammatory profile of peritoneal macrophages and subcutaneous adipose tissue (SAT) were evaluated. The PPAR-γ deletion did not affect body composition or physical test performance in control diet fed animals, however the training not only provided metabolic but also the immune response enhancements on knockout animals. The induction of obesity promoted hypertrophy in the SAT, though the inflammatory profile was not exacerbated in KO animals. Peritoneal macrophages of KO animals exhibited a marked inflammatory environment after LPS stimulation. The moderate aerobic training program protected both genotypes from weight gain, reduced caloric intake and hypertrophy of SAT from KO animals. Training modulated cytokine production in peritoneal macrophages, although M2 polarization exhibited attenuation in the absence of PPAR-γ. In summary, our findings demonstrate an important modulatory role of the transcription factor PPAR-γ in macrophages M2 markers, but its deletion did not prevent the exercise-mediated anti-inflammatory effect. (AU)

• FAPESP's process: 14/01246-6 - Evaluation of immune metabolic response in peritoneal macrophages from obese mice: role of physical exercise and PPAR-gamma
• Grantee: Loreana Sanches Silveira
• Support Opportunities: Scholarships in Brazil - Doctorate