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Journal of Lipid Research, Vol. 48, 1069-1077, May 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology

NF-B is important for TNF--induced lipolysis in human adipocytes

Jurga Laurencikiene^1,*, Vanessa van Harmelen^1,*, Elisabet Arvidsson Nordström^*, Andrea Dicker^*, Lennart Blomqvist^*, Erik Näslund, Dominique Langin^,**,, Peter Arner^* and Mikael Rydén^2,*

^* Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, 141 86 Stockholm, Sweden
Department of Surgery, Karolinska Institutet, Danderyd Hospital, 182 88, Stockholm, Sweden
Institut National de la Santé et de la Recherche Médicale U586, Unité de Recherches sur les Obésités, Toulouse, F-31432 France
^** Université Paul Sabatier, Institut Louis Bugnard IFR31, Toulouse, F-31432 France
Centre Hospitalier Universitaire de Toulouse, Biochimie, Institut Fédératif de Biologie de Purpan, Toulouse, F-31059 France

Published, JLR Papers in Press, February 1, 2007.

¹ J. Laurencikiene and V. van Harmelen contributed equally to this work.

² To whom correspondence should be addressed. e-mail: mikael.ryden{at}ki.se

Tumor necrosis factor- (TNF-) 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-, nuclear factor-B (NF-B), has not been recognized. We explored the role of NF-B in TNF--induced lipolysis of human fat cells. Primary cultures of human adipocytes were incubated in the presence of a cell-permeable peptide that inhibits NF-B signaling (WP). Incubation with WP, but not with a biologically inactive peptide (MP), abolished the nuclear translocation of NF-B and effectively abrogated TNF--induced lipolysis in a concentration-dependent manner. Western blot analysis demonstrated that although TNF- per se reduced mainly PLIN protein expression, TNF- 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- in the presence of NF-B inhibition. This was confirmed in gene reporter assays using human PLIN and HSL promoter constructs. We conclude that in the presence of NF-B inhibition, TNF--mediated lipolysis is reduced, which suggests that NF-B is essential for retained human fat cell lipolysis.

Supplementary key words tumor necrosis factor- • nuclear factor-B • signal • differentiation

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