NF-κB is important for TNF-α-induced lipolysis in human adipocytes

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 kappa beta (NF-kappa beta), has not been recognized. We explored the role of NF-kappa beta 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-kappa beta signaling (WP). Incubation with WP, but not with a biologically inactive peptide (MP), abolished the nuclear translocation of NF-kappa beta 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-kappa beta inhibition. This was confirmed in gene reporter assays using human PLIN and HSL promoter constructs. We conclude that in the presence of NF-kappa beta inhibition, TNF-alpha- mediated lipolysis is reduced, which suggests that NF-kappa beta is essential for retained human fat cell lipolysis.