Transcriptional Analysis of FOXO1, C/EBP-α and PPAR-γ2 Genes and Their Association with Obesity-Related Insulin Resistance

Genes (Basel). 2019 Sep 12;10(9):706. doi: 10.3390/genes10090706.

Abstract

Background: Obesity is associated with several comorbid disorders, ranging from cardiovascular diseases to insulin resistance. In this context, visceral adipose tissue (VAT) seems to have a close connection with insulin resistance. In our study, we hypothesized that the expression profile of key adipogenic genes, such as proliferator-activated receptor γ type 2 (PPAR-γ2), CCAAT/enhancer-binding protein type α (C/EBP-α), and forkhead box protein class O type 1 (FOXO1) in VAT should shed light on their association with obesity-related insulin resistance.

Methods: To test this idea, we studied the expression profile of C/EBP-α, FOXO1 and PPAR-γ2 in VAT from non-obese individuals, and low insulin (LIR-MO) and high insulin morbidly obese (HIR-MO) subjects, through a combination of RT-qPCR, co-immunoprecipitation, ELISA, Western blot analysis and EMSA assays.

Results: Our results show that C/EBP-α and PPAR-γ2 were down-expressed in HIR-MO individuals, while FOXO1 was overexpressed. In addition, the PPAR-γ2-RXR-α heterodimer showed weak activity and bound weakly to the putative IGFBP-2-PPRE promoter sequence in VAT from HIR-MO subjects when compared with LIR-MO individuals.

Conclusions: These results show that PPAR-γ2, C/EBP-α, FOXO1 and IGFBP-2 have a close relationship with insulin resistance in VAT of morbidly obese individuals.

Keywords: C/EBP-α; FOXO1; IGFBP-2; PPAR-γ2; insulin resistance; obesity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • CCAAT-Enhancer-Binding Protein-alpha / genetics*
  • CCAAT-Enhancer-Binding Protein-alpha / metabolism
  • Female
  • Forkhead Box Protein O1 / genetics*
  • Forkhead Box Protein O1 / metabolism
  • Humans
  • Insulin Resistance*
  • Insulin-Like Growth Factor Binding Protein 2 / genetics
  • Insulin-Like Growth Factor Binding Protein 2 / metabolism
  • Male
  • Middle Aged
  • Obesity, Morbid / genetics*
  • Obesity, Morbid / metabolism
  • PPAR gamma / genetics*
  • PPAR gamma / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • CCAAT-Enhancer-Binding Protein-alpha
  • FOXO1 protein, human
  • Forkhead Box Protein O1
  • IGFBP2 protein, human
  • Insulin-Like Growth Factor Binding Protein 2
  • PPAR gamma
  • RNA, Messenger