PPAR-γ Agonist Ameliorates Liver Pathology Accompanied by Increasing Regulatory B and T Cells in High-Fat-Diet Mice

Objective: Peroxisome proliferator-activated receptor ( PPAR)- gamma plays critical roles in human metabolic disorders. However, the mechanism remains incompletely understood. Regulatory cells contribute to these metabolic improvements; therefore, whether PPAR-c agonist regulates regulatory cells was investigated. Methods: C57BL/6J mice received a normal or high-fat diet (HFD) with or without pioglitazone treatment. Mice were sacrificed for detecting the metabolic parameters. Lymphocytes from spleen and visceral adipose tissue (VAT) were collected and analyzed for ST2(+)Tregs and Bregs by flow cytometry. IL-10 in the liver or VAT was detected by immunofluorescence and ELISA. Correlation analysis between IL-10 and liver weight or serum total cholesterol was made by Pearson correlation analysis. Results: Pioglitazone increased VAT weight but reduced serum total cholesterol, hepatic steatosis, and cholesterol crystallization formation. Pioglitazone treatment enhanced ST2(+)Tregs and Bregs in the VAT and spleen of HFD-fed mice (all P < 0.05). Pioglitazone treatment increased IL-10 in the livers or VAT of HFD-fed mice ( all P < 0.05). The expression of IL-10 in the liver was significantly negatively correlated with liver weight or serum total cholesterol in pioglitazone-treated HFD-fed mice (r(2) = 0.74, P < 0.05; r(2) = 0.58, P < 0.05). Conclusions: PPAR-gamma signaling plays a critical role in the regulation of metabolic disorders through promoting regulatory cell response.