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TNF-α reduces g0s2 expression and stimulates lipolysis through PPAR-γ inhibition in 3T3-L1 adipocytes.
- Source :
-
Cytokine . Oct2014, Vol. 69 Issue 2, p196-205. 10p. - Publication Year :
- 2014
-
Abstract
- Tumor necrosis factor-α (TNF-α) is a multifunctional cytokine that acts as a mediator of obesity-linked insulin resistance (IR). It is commonly accepted that macrophage-derived TNF-α acts in a paracrine manner on adjacent adipocytes, induces lipolysis, which contributes to obesity-linked hyperglycemia. Several studies suggested that G0/G1 switch gene 2 (g0s2) was up-regulated during adipogenesis, and its protein could be degraded in response to TNF-α stimulation. The aim of the present work was to investigate the transcriptional regulation of g0s2 by TNF-α stimulation. In this study, 3T3-L1 pre-adipocytes were differentiated, and treated with TNF-α for 24h. The effects of TNF-α on lipolysis and lipase expression were then examined. Our results revealed that TNF-α exerted dose- and time-dependent lipolytic effects, which could be partially reversed by overexpression of g0s2 and peroxisome proliferator-activated receptor-γ (ppar-γ). In addition, TNF-α treatment significantly reduced the expression of adiponectin, ppar-γ, hormone-sensitive Lipase (hsl), adipose triglyceride lipase (atgl) as well as ATGL co-factors. Interestingly, TNF-α significantly decreased adiponectin and PPAR-γ protein levels, while treatment with the proteasomal inhibitor MG-132 maintained PPAR-γ levels. Degradation of PPAR-γ almost completely abolished the binding of PPAR-γ to the g0s2 promoter in adipocytes treated with TNF-α. We propose that proteasomal degradation of PPAR-γ and the reduction of g0s2 content are permissive for prolonged TNF-α induced lipolysis. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10434666
- Volume :
- 69
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Cytokine
- Publication Type :
- Academic Journal
- Accession number :
- 97448697
- Full Text :
- https://doi.org/10.1016/j.cyto.2014.06.005