Regulation of urea synthesis during the acute-phase response in rats
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Regulation of urea synthesis during the acute-phase response in rats. / Thomsen, Karen Louise; Jessen, Niels; Møller, Andreas Buch; Aagaard, Niels Kristian; Grønbæk, Henning; Holst, Jens Juul; Vilstrup, Hendrik.
In: American Journal of Physiology: Gastrointestinal and Liver Physiology, Vol. 304, No. 7, 01.04.2013, p. G680-6.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Regulation of urea synthesis during the acute-phase response in rats
AU - Thomsen, Karen Louise
AU - Jessen, Niels
AU - Møller, Andreas Buch
AU - Aagaard, Niels Kristian
AU - Grønbæk, Henning
AU - Holst, Jens Juul
AU - Vilstrup, Hendrik
PY - 2013/4/1
Y1 - 2013/4/1
N2 - The acute-phase response is a catabolic event involving increased waste of amino-nitrogen (N) via hepatic urea synthesis, despite an increased need for amino-N incorporation into acute-phase proteins. This study aimed to clarify the regulation of N elimination via urea during different phases of the tumor necrosis factor-α (TNF-α)-induced acute-phase response in rats. We used four methods to study the regulation of urea synthesis: We examined urea cycle enzyme mRNA levels in liver tissue, the hepatocyte urea cycle enzyme proteins, the in vivo capacity of urea-N synthesis (CUNS), and known humoral regulators of CUNS at 1, 3, 24, and 72 h after TNF-α injection (25 μg/kg iv rrTNF-α) in rats. Serum acute-phase proteins and their liver mRNA levels were also measured. The urea cycle enzyme mRNA levels acutely decreased and then gradually normalized, whereas the urea cycle enzyme proteins remained essentially unchanged over time. The CUNS rose after 3 h and then normalized. The acute-phase response was fully activated at 24 h with markedly increased serum levels of the acute-phase proteins. TNF-α acutely upregulated the CUNS. Later, despite the fully established 24-h acute-phase response and the decreased activity of the urea cycle enzyme genes, there was no change in the urea cycle enzyme proteins or the CUNS. Thus in no phase after the initiation of the acute-phase response was in vivo urea synthesis orchestrated in combination with acute-phase protein synthesis so as to limit N waste.
AB - The acute-phase response is a catabolic event involving increased waste of amino-nitrogen (N) via hepatic urea synthesis, despite an increased need for amino-N incorporation into acute-phase proteins. This study aimed to clarify the regulation of N elimination via urea during different phases of the tumor necrosis factor-α (TNF-α)-induced acute-phase response in rats. We used four methods to study the regulation of urea synthesis: We examined urea cycle enzyme mRNA levels in liver tissue, the hepatocyte urea cycle enzyme proteins, the in vivo capacity of urea-N synthesis (CUNS), and known humoral regulators of CUNS at 1, 3, 24, and 72 h after TNF-α injection (25 μg/kg iv rrTNF-α) in rats. Serum acute-phase proteins and their liver mRNA levels were also measured. The urea cycle enzyme mRNA levels acutely decreased and then gradually normalized, whereas the urea cycle enzyme proteins remained essentially unchanged over time. The CUNS rose after 3 h and then normalized. The acute-phase response was fully activated at 24 h with markedly increased serum levels of the acute-phase proteins. TNF-α acutely upregulated the CUNS. Later, despite the fully established 24-h acute-phase response and the decreased activity of the urea cycle enzyme genes, there was no change in the urea cycle enzyme proteins or the CUNS. Thus in no phase after the initiation of the acute-phase response was in vivo urea synthesis orchestrated in combination with acute-phase protein synthesis so as to limit N waste.
KW - Acute-Phase Reaction
KW - Animals
KW - Blood Glucose
KW - Corticosterone
KW - Female
KW - Glucagon
KW - I-kappa B Proteins
KW - Insulin
KW - Liver
KW - RNA, Messenger
KW - Rats
KW - Rats, Wistar
KW - Tumor Necrosis Factor-alpha
KW - Urea
U2 - 10.1152/ajpgi.00416.2012
DO - 10.1152/ajpgi.00416.2012
M3 - Journal article
C2 - 23392238
VL - 304
SP - G680-6
JO - American Journal of Physiology: Gastrointestinal and Liver Physiology
JF - American Journal of Physiology: Gastrointestinal and Liver Physiology
SN - 0193-1857
IS - 7
ER -
ID: 45840266