Effect of tumor necrosis factor α on cholesterol efflux in adipocytes

Background: The pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) has multiple effects on adipocyte, including cell differentiation, lipolysis and the production of adipokines. It is not known whether TNF-alpha has effect on cholesterol efflux in adipocyte. Methods: Rabbit subcutaneous adipocytes were incubated with 5, 10, 20 ng/ml TNF-alpha for 24 h. The cholesterol efflux onto apoAI was assessed, and the related peroxisome proliferators-activated receptor (PPAR) gamma, liver X receptor (LXR) alpha and ATP binding cassette transporter A1 (ABCA1) mRNA expression in adipocytes were quantified by reverse transcription polymerase chain reaction. Results: Treatment of adipocytes with 5 or 10 ng/ml TNF-alpha for 24 h increased cholesterol efflux, and the effect of 10 ng/ml TNF-alpha was significant higher than the control group. In contrast, 20 ng/tul TNF-alpha decreased cholesterol efflux compared with 10 ng/ml TNF-alpha. The expression of ABCA1 was increased by 5 ng/ml or 10 ng/ml TNF-alpha compared with control group, and was inhibited by 20 ng/ml TNF-alpha. The PPAR gamma and LXR alpha mRNA were also significantly induced by 10 ng/ml TNF-alpha and down regulated by higher TNF-alpha concentration. After pre-treated by GW9662, the expression of PPAR gamma induced by TNF-alpha was partially prevented, subsequent to the down-regulation of LXR alpha and ABCA1. Conclusions: TNF-alpha affects cholesterol efflux and ABCA1 expression of adipocytes, and the pathway of PPAR gamma-LXR alpha-ABCA1 is probably involved. (C) 2007 Elsevier B.V. All rights reserved.