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

• Published in: Genes Vol. 10; no. 9; p. 706
• Main Authors: Boughanem, Hatim, Cabrera-Mulero, Amanda, Millán-Gómez, Mercedes, Garrido-Sánchez, Lourdes, Cardona, Fernando, Tinahones, Francisco José, Moreno-Santos, Inmaculada, Macías-González, Manuel
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 12.09.2019; MDPI
• Subjects: Adipocytes; Adipose tissue; Adult; Aged; Alzheimer's disease; Antibodies; Binding sites; Biotechnology; Cardiovascular disease; Cardiovascular diseases; CCAAT-Enhancer-Binding Protein-alpha - genetics; CCAAT-Enhancer-Binding Protein-alpha - metabolism; CCAAT/enhancer-binding protein; Cholesterol; Diabetes; Enzyme-linked immunosorbent assay; Female; Forkhead Box Protein O1 - genetics; Forkhead Box Protein O1 - metabolism; Forkhead protein; FOXO1 protein; Gastrointestinal surgery; Gene expression; genes; Glucose; Humans; Immunoprecipitation; Infectious diseases; Insulin; Insulin Resistance; Insulin-Like Growth Factor Binding Protein 2 - genetics; Insulin-Like Growth Factor Binding Protein 2 - metabolism; Insulin-like growth factor-binding protein 2; Laboratories; Male; Metabolism; Middle Aged; Obesity; Obesity, Morbid - genetics; Obesity, Morbid - metabolism; Peroxisome proliferator-activated receptors; PPAR gamma - genetics; PPAR gamma - metabolism; precipitin tests; promoter regions; Proteins; quantitative polymerase chain reaction; Retinoid X receptors; reverse transcriptase polymerase chain reaction; RNA, Messenger - genetics; RNA, Messenger - metabolism; Transcription; transcription (genetics); Transcription factors; Western blotting; United States > US; Switzerland; Germany; Spain; IGFBP-2; C/EBP-α; PPAR-γ2; insulin resistance; FOXO1; obesity
• ISSN: 2073-4425; 2073-4425
• DOI: 10.3390/genes10090706

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.