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)-γ plays critical roles in human metabolic disorders. However, the mechanism remains incompletely understood. Regulatory cells contribute to these metabolic improvements; therefore, whether PPAR-γ 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  = 0.74, P < 0.05; r  = 0.58, P < 0.05).

CONCLUSIONS

PPAR-γ signaling plays a critical role in the regulation of metabolic disorders through promoting regulatory cell response.