Related Experiment Video
Updated: Mar 8, 2026
Incorporation of a Survivable Liver Biopsy Procedure in Mice to Assess Non-alcoholic Steatohepatitis NASH Resolution
Published on: April 16, 2019
PPAR-γ agonist ameliorates liver pathology accompanied by increasing regulatory B and T cells in high-fat-diet mice
Zhipeng Xu1, Gang Wang2, Yuxiao Zhu1
1Department of Pathogen Biology and Immunology, Jiangsu Province Key Laboratory of Modern Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
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 (r2 = 0.74, P < 0.05; r2 = 0.58, P < 0.05).
Conclusions:
PPAR-γ signaling plays a critical role in the regulation of metabolic disorders through promoting regulatory cell response.
Insights
Peroxisome proliferator-activated receptor (PPAR)-γ agonists like pioglitazone promote regulatory cells, improving metabolic disorders. This study shows PPAR-γ signaling enhances regulatory T cells (Tregs) and Bregs, reducing cholesterol and liver fat.
Area of Science:
- Metabolic disorders research
- Immunology and metabolic interactions
- Pharmacology of metabolic disease
Background:
- Peroxisome proliferator-activated receptor (PPAR)-γ is crucial in metabolic disorders, but its mechanisms are not fully understood.
- Regulatory cells are known to improve metabolic health, prompting investigation into their regulation by PPAR-γ agonists.
Purpose of the Study:
- To investigate whether PPAR-γ agonists regulate regulatory cells in the context of metabolic disorders.
- To elucidate the role of PPAR-γ signaling in metabolic improvements mediated by regulatory cell responses.
Main Methods:
- C57BL/6J mice were fed a high-fat diet (HFD) with or without pioglitazone.
- Metabolic parameters, ST2+ Tregs, Bregs in spleen and visceral adipose tissue (VAT), and IL-10 levels were analyzed.
- Flow cytometry, immunofluorescence, ELISA, and Pearson correlation analysis were employed.
Main Results:
- Pioglitazone treatment reduced serum total cholesterol, hepatic steatosis, and cholesterol crystallization.
- Enhanced populations of ST2+ Tregs and Bregs were observed in VAT and spleen of HFD-fed mice treated with pioglitazone.
- Increased IL-10 expression in the liver and VAT correlated negatively with liver weight and serum total cholesterol.
Conclusions:
- PPAR-γ signaling is critical in managing metabolic disorders by promoting regulatory cell responses.
- Pioglitazone enhances regulatory cell populations and IL-10 production, contributing to metabolic improvements.
- These findings highlight a novel mechanism for PPAR-γ in metabolic regulation via immune cell modulation.
