Effect of lipopolysaccharide on in vivo and genetic regulation of rat urea synthesis.
BACKGROUND
The acute phase response causes a negative nitrogen balance. It is unknown whether this involves regulation of hepatic urea synthesis.


METHODS
We examined the in vivo capacity of urea nitrogen synthesis (CUNS), mRNA levels of urea cycle enzyme genes and galactose elimination capacity (GEC) during moderate and severe acute phase response induced by low- and high-dose lipopolysaccharide (LPS) in rats.


RESULTS
Low-dose LPS doubled CUNS (P<0.05), decreased the mRNA level of the rate-limiting urea cycle enzyme (arginino succinate synthetase (ASS) by 26% (P<0.05) and did not change GEC. High-dose LPS did not change CUNS, decreased the mRNA level of the flux-generating enzyme carbamoyl phosphate synthetase (CPS) by 11% (P<0.05) and the rate-limiting urea cycle enzyme (ASS) by 27% (P<0.05) and almost halved GEC (P<0.05).


CONCLUSIONS
The moderate acute phase response up-regulated in vivo urea synthesis but had the opposite effect on gene level. The severe acute phase response decreased the functional liver mass that attenuated the increase in urea synthesis.
Nielsen
Susanne Schouw
SS
Department of Medicine V, Aarhus University Hospital, DK-8000 Aarhus C, Denmark. schouw@akhphd.au.dk
Grøfte
Thorbjørn
T
Tygstrup
Niels
N
Vilstrup
Hendrik
H
D000818:Animals; D001124:Argininosuccinate Synthase / Q000235:genetics / Q000378:metabolism; D002222:Carbamoyl-Phosphate Synthase (Ammonia) / Q000235:genetics / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D004798:Enzymes / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000276:immunology; D015971:Gene Expression Regulation, Enzymologic; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008136:Longevity / Q000187:drug effects; D008297:Male; D009961:Orosomucoid / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014508:Urea / Q000378:metabolism*; D000511:alpha-Macroglobulins / Q000235:genetics / Q000378:metabolism
D004798:Enzymes; D008070:Lipopolysaccharides; D009961:Orosomucoid; D012333:RNA, Messenger; D000511:alpha-Macroglobulins; D014508:Urea; D002222:Carbamoyl-Phosphate Synthase (Ammonia); D001124:Argininosuccinate Synthase