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Department of Physiology and Lipid Research Unit, Laval University Hospital Research Center, Quebec, Canada G1V 4G2
The aim of the present study was to investigate
the mechanism of adipose tissue inducible nitric oxide synthase (iNOS)
induction in endotoxemia. Systemic administration of the bacterial
endotoxin lipopolysaccharide (LPS) to rats for
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. iNOS activity was also found to be
greatly enhanced in both white and brown adipose tissues of LPS-treated
rats (an ~12- to 20-fold increase). Treatment of cultured 3T3-L1
adipocytes with LPS, tumor necrosis factor-
(TNF-
), or
interferon-
(IFN-
) alone failed to induce iNOS activity. However,
when used in combination, TNF-
, IFN-
, and LPS markedly and
synergistically increased iNOS activity in these cells. In conclusion,
these results suggest that adipose tissue is a major site of iNOS
expression in endotoxemia. Our data further indicate that iNOS
induction can be reproduced in vitro in cultured adipocytes and that a
concerted action of cytokines and endotoxin is needed for maximal
activation of the enzyme.
lipopolysaccharide; tumor necrosis factor-
; interferon-
; adipocytes; skeletal muscle; liver; kidney
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