Mechanism of adipose tissue iNOS induction in endotoxemia

The aim of the present study was to investigate the mechanism of adipose ti ssue inducible nitric oxide synthase (iNOS) induction in endotoxemia. Syste mic administration of the bacterial endotoxin lipopolysaccharide (LPS) to r ats for less than or equal to 8 h markedly increased iNOS mRNA and protein levels in white and brown adipose tissues. This effect was comparable to or greater than the induction of iNOS in liver, kidney, or skeletal muscle. i NOS activity was also found to be greatly enhanced in both white and brown adipose tissues of LPS-treated rats (an similar to 12- to 20-fold increase) . Treatment of cultured 3T3-L1 adipocytes with LPS, tumor necrosis factor-a lpha (TNF-alpha), or interferon-gamma (IFN-gamma) alone failed to induce iN OS activity. However, when used in combination, TNF-alpha, IFN-gamma, and L PS markedly and synergistically increased iNOS activity in these cells. In conclusion, these results suggest that adipose tissue is a major site of iN OS expression in endotoxemia. Our data further indicate that iNOS induction can be reproduced in vitro in cultured adipocytes and that a concerted act ion of cytokines and endotoxin is needed for maximal activation of the enzy me.