Effects of pioglitazone mediated activation of PPAR-γ on CIDEC and obesity related changes in mice

PLoS One. 2014 Sep 11;9(9):e106992. doi: 10.1371/journal.pone.0106992. eCollection 2014.

Abstract

Objective: Obesity is a metabolic disorder that can lead to high blood pressure, increased blood cholesterol and triglycerides, insulin resistance, and diabetes mellitus. The aim was to study the effects of pioglitazone mediated sensitization of peroxisome proliferator-activated receptor gamma (PPAR-γ) on the relationship of Cell death-inducing DFFA-like effector C (CIDEC) with obesity related changes in mice.

Methods: Sixty C57B/L6 mice weighing 10-12g at 3 weeks of age were randomly divided into 3 groups. Mice in Group 1 were fed on normal diet (ND) while Group 2 mice were given high fat diet (HFD), and Group 3 mice were given high fat diet and treated with Pioglitazone (HFD+P). Body weight, length and level of blood sugar were measured weekly. Quantitative real-time PCR, fluorescence microscopy, and ELISA were performed to analyze the expression of CIDEC and PPAR-γ in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT).

Results: Body weight and length of mice increased gradually with time in all groups. Blood sugar in HFD mice started to increase significantly from the mid of late phase of obesity while pioglitazone attenuated blood sugar level in HFD+P mice. The mRNA expressions and protein levels of PPAR-γ and CIDEC genes started to increase in HFD mice as compared to ND mice and decreased gradually during the late phase of obesity in VAT. Pioglitazone enhanced the expression of PPAR-γ and CIDEC genes in HFD+P mice even during the late phase of obesity.

Conclusion: It is insinuated that VAT is associated with late phase obesity CIDEC decrease and insulin resistance, while pioglitazone enhances CIDEC through activation of PPAR-γ, increases its expression, and decreases lipolysis, hence preventing an increase of blood sugar in mice exposed to HFD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose
  • Diet, High-Fat
  • Gene Expression Regulation / drug effects
  • Humans
  • Insulin Resistance / genetics
  • Intra-Abdominal Fat / drug effects
  • Intra-Abdominal Fat / metabolism
  • Intra-Abdominal Fat / pathology
  • Lipolysis / drug effects
  • Mice
  • Obesity / drug therapy
  • Obesity / genetics*
  • Obesity / pathology
  • PPAR gamma / biosynthesis*
  • Pioglitazone
  • Proteins / genetics*
  • Subcutaneous Fat / drug effects
  • Subcutaneous Fat / metabolism
  • Subcutaneous Fat / pathology
  • Thiazolidinediones / administration & dosage*

Substances

  • Blood Glucose
  • PPAR gamma
  • Proteins
  • Thiazolidinediones
  • fat-specific protein 27, mouse
  • Pioglitazone

Grants and funding

The project was supported by the National Natural Science Foundation of China (81172689), The Major Research Funding Schemes of 2nd Affiliated Hospital of Xi'an Jiaotong University YJ (ZDJH) 201303(3), Higher Education Commission (HEC) Pakistan, and the Shaanxi Province International Co-operational Foundation of China. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.