TNF-α inhibits PPARß/δ activity and SIRT1 expression through NF-κB in human adipocytes.
Biochim Biophys Acta
; 1821(9): 1177-85, 2012 Sep.
Article
en En
| MEDLINE
| ID: mdl-22683888
ABSTRACT
The mechanisms linking low-grade chronic inflammation with obesity-induced insulin resistance have only been partially elucidated. PPARß/δ and SIRT1 might play a role in this association. In visceral adipose tissue (VAT) from obese insulin-resistant patients we observed enhanced p65 nuclear translocation and elevated expression of the pro-inflammatory cytokines TNF-α and IL-6 compared to control subjects. Inflammation was accompanied by a reduction in the levels of SIRT1 protein and an increase in PPARß/δ mRNA levels. Stimulation of human mature SGBS adipocytes with TNF-α caused similar changes in PPARß/δ and SIRT1 to those reported in obese patients. Unexpectedly, PPAR DNA-binding activity and the expression of PPARß/δ-target genes was reduced following TNF-α stimulation, suggesting that the activity of this transcription factor was inhibited by cytokine treatment. Interestingly, the PPARß/δ ligand GW501516 prevented the expression of inflammatory markers and the reduction in the expression of PPARß/δ-target genes in adipocytes stimulated with TNF-α. Consistent with a role for NF-κB in the changes caused by TNF-α, treatment with the NF-κB inhibitor parthenolide restored PPAR DNA-binding activity, the expression of PPARß/δ-target genes and the expression of SIRT1 and PPARß/δ. These findings suggest that the reduction in PPARß/δ activity and SIRT1 expression caused by TNF-α stimulation through NF-κB helps perpetuate the inflammatory process in human adipocytes.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Regulación Enzimológica de la Expresión Génica
/
Factor de Necrosis Tumoral alfa
/
Adipocitos
/
Síndrome Metabólico
/
PPAR-beta
/
PPAR delta
/
Factor de Transcripción ReIA
/
Sirtuina 1
/
Obesidad
Tipo de estudio:
Clinical_trials
Límite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Biochim Biophys Acta
Año:
2012
Tipo del documento:
Article
País de afiliación:
España