NF-kappaB is important for TNF-alpha-induced lipolysis in human adipocytes.

Abstract : Tumor necrosis factor-alpha (TNF-alpha) promotes lipolysis in mammal adipocytes via the mitogen-activated protein kinase (MAPK) family, resulting in reduced expression/function of perilipin (PLIN). The role of another pivotal intracellular messenger activated by TNF-alpha, nuclear factor-kappaB (NF-kappaB), has not been recognized. We explored the role of NF-kappaB in TNF-alpha-induced lipolysis of human fat cells. Primary cultures of human adipocytes were incubated in the presence of a cell-permeable peptide that inhibits NF-kappaB signaling (WP). Incubation with WP, but not with a biologically inactive peptide (MP), abolished the nuclear translocation of NF-kappaB and effectively abrogated TNF-alpha-induced lipolysis in a concentration-dependent manner. Western blot analysis demonstrated that although TNF-alpha per se reduced mainly PLIN protein expression, TNF-alpha in the presence of WP resulted in a pronounced combined reduction of both hormone-sensitive lipase (HSL) and PLIN protein. The expression of a set of other lipolytic or adipocyte-specific proteins was not affected. The regulation was presumably at the transcriptional level, because mRNA expression for HSL and PLIN was markedly reduced with TNF-alpha in the presence of NF-kappaB inhibition. This was confirmed in gene reporter assays using human PLIN and HSL promoter constructs. We conclude that in the presence of NF-kappaB inhibition, TNF-alpha-mediated lipolysis is reduced, which suggests that NF-kappaB is essential for retained human fat cell lipolysis.
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The Journal of Lipid Research, 2007, 48 (5), pp.1069-77. 〈10.1194/jlr.M600471-JLR200〉
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Soumis le : mardi 11 août 2009 - 15:29:31
Dernière modification le : mardi 25 août 2009 - 08:46:01

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Jurga Laurencikiene, Vanessa Van Harmelen, Elisabet Arvidsson Nordström, Andrea Dicker, Lennart Blomqvist, et al.. NF-kappaB is important for TNF-alpha-induced lipolysis in human adipocytes.. The Journal of Lipid Research, 2007, 48 (5), pp.1069-77. 〈10.1194/jlr.M600471-JLR200〉. 〈inserm-00409661〉

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