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Journal of Lipid Research, Vol 36, 1254-1263, Copyright © 1995 by Lipid Research, Inc.
H Ly, OL Francone, CJ Fielding, JK Shigenaga, AH Moser, C Grunfeld and KR Feingold
Endotoxin (LPS) administration, which mimics infection, stimulates the
production of many cytokines, including TNF, that are thought to mediate
the alterations in lipid metabolism that occur during infection. The aims
of this study were to determine the effect of LPS or TNF administration on
plasma LCAT activity and hepatic LCAT mRNA levels in Syrian hamsters.
Plasma LCAT activity was decreased 8 h after LPS administration, reached a
maximum level of inhibition at 16 h which persisted for at least 24 h, at
which time the activity was 53% of control values. The decrease in plasma
LCAT activity was first seen at an LPS dose of 0.01 microgram/100 g body
weight and reached a maximum at 50-100 micrograms/100 g body weight. The
ratio of free to esterified cholesterol in the plasma increased in the
LPS-treated animals. Moreover, LPS administration decreased LCAT mRNA
levels in the liver. The decrease in hepatic LCAT mRNA levels preceded the
decrease in plasma LCAT activity. Additionally, TNF treatment (16.7
micrograms/100 g body weight) decreased plasma LCAT activity by 35% and
LCAT mRNA levels in the liver by 60% 16 h after administration. Lastly, in
cultured rat H35 hepatocytes, TNF decreased LCAT mRNA levels in the liver
by 60% 16 h after administration. Lastly, in cultured rat H35 hepatocytes,
TNF decreased LCAT mRNA levels by 50% with a 1/2 maximal dose of
approximately 1 ng/ml. Thus, plasma LCAT activity and hepatic mRNA levels
are decreased by LPS or TNF treatment. LCAT is a member of a group of
proteins that affect lipid and lipoprotein metabolism whose levels are
altered during the host's acute phase response.
ARTICLES
Endotoxin and TNF lead to reduced plasma LCAT activity and decreased hepatic LCAT mRNA levels in Syrian hamsters
Department of Medicine, University of California, San Francisco, USA.
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