Mechanism of adipose tissue iNOS induction in endotoxemia.
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 approximately 12- to 20-fold increase). Treatment of cultured 3T3-L1 adipocytes with LPS, tumor necrosis factor-alpha (TNF-alpha), or interferon-gamma (IFN-gamma) alone failed to induce iNOS activity. However, when used in combination, TNF-alpha, IFN-gamma, 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.
Kapur
S
S
Department of Physiology and Lipid Research Unit, Laval University Hospital Research Center, Quebec, Canada G1V 4G2.
Marcotte
B
B
Marette
A
A
D016475:3T3 Cells; D017667:Adipocytes / Q000201:enzymology; D000273:Adipose Tissue / Q000201:enzymology*; D002001:Adipose Tissue, Brown / Q000201:enzymology*; D000818:Animals; D019446:Endotoxemia / Q000201:enzymology*; D004790:Enzyme Induction / Q000187:drug effects; D004926:Escherichia coli; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II; D009928:Organ Specificity; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C496318:Nos2 protein, rat