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