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

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 gene...

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Detalles Bibliográficos
Autores: Boughanem, Hatim, Cabrera-Mulero, Amanda, Millán-Gómez, Mercedes, Garrido-Sánchez, Lourdes, Cardona, Fernando, Tinahones, Francisco José, Moreno-Santos, Inmaculada, Macías-González, Manuel
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/17908
Acceso en línea:http://hdl.handle.net/20.500.12105/17908
Access Level:acceso abierto
Palabra clave:C/EBP-α
FOXO1
IGFBP-2
PPAR-γ2
Insulin resistance
Obesity
Adult
Aged
CCAAT-Enhancer-Binding Protein-alpha
Female
Forkhead Box Protein O1
Humans
Insulin Resistance
Insulin-Like Growth Factor Binding Protein 2
Male
Middle Aged
Obesity, Morbid
PPAR gamma
RNA, Messenger
Descripción
Sumario: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. 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. 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. 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.