Endotoxin-induced hypertriglyceridemia is mediated by suppression of lipoprotein lipase at a post-transcriptional level.
Previous studies have demonstrated that endotoxin/lipopolysaccharide treatment causes a decrease in adipose tissue and heart lipoprotein lipase (LPL) activities in rats, producing hypertriglyceridemia in these animals. To examine the mechanisms for this effect of endotoxin, we studied the effects of endotoxin administration on LPL mRNA, and LPL synthetic rates and activity in rat adipose tissue and heart. Endotoxin treatment (i.p., 3 mg/100 g body weight or higher doses) produced a pronounced increase in serum triglycerides associated with a 65% decrease in adipose tissue and heart LPL activities within 7 h. Fast protein liquid chromatography (FPLC), used to separate lipoproteins in rat serum, showed that the increase in triglyceride was all in the very low density lipoprotein fraction which was accompanied by a concomitant decrease in high density lipoprotein. In contrast, there was no change in adipose tissue or heart LPL mRNA up to 24 h after treatment and no change in adipose tissue LPL synthetic rate, as measured by L-[35S]methionine incorporation and immunoprecipitation. Plasma insulin levels remained unchanged. The results indicate that endotoxin-induced hypertriglyceridemia in rats can be attributed to an impaired triglyceride clearance associated with a decrease of LPL activity mediated at a post-transcriptional level.
Gouni
I
I
Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030.
Oka
K
K
Etienne
J
J
Chan
L
L
D000273:Adipose Tissue / Q000187:drug effects / Q000201:enzymology; D000818:Animals; D001424:Bacterial Infections / Q000150:complications / Q000201:enzymology; D004731:Endotoxins / Q000633:toxicity*; D006321:Heart / Q000187:drug effects; D015228:Hypertriglyceridemia / Q000201:enzymology* / Q000209:etiology*; D008070:Lipopolysaccharides / Q000633:toxicity; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000201:enzymology; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D004731:Endotoxins; D008070:Lipopolysaccharides; D012333:RNA, Messenger; C044101:endotoxin, Escherichia coli; D008071:Lipoprotein Lipase