PPAR-γ agonist ameliorates liver pathology accompanied by increasing regulatory B and T cells in high-fat-diet mice

Obesity (Silver Spring). 2017 Mar;25(3):581-590. doi: 10.1002/oby.21769. Epub 2017 Feb 2.

Abstract

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.

MeSH terms

  • Animals
  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / metabolism
  • Cholesterol / blood
  • Diet, High-Fat
  • Fatty Liver / drug therapy*
  • Fatty Liver / metabolism
  • Fatty Liver / pathology
  • Interleukin-10 / metabolism
  • Intra-Abdominal Fat / drug effects
  • Intra-Abdominal Fat / metabolism
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • PPAR gamma / agonists*
  • PPAR gamma / metabolism
  • Pioglitazone
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / metabolism
  • Thiazolidinediones / pharmacology*
  • Thiazolidinediones / therapeutic use

Substances

  • PPAR gamma
  • Thiazolidinediones
  • Interleukin-10
  • Cholesterol
  • Pioglitazone