Pretreatment of starved rats with ornithine alpha-ketoglutarate: effects on hepatic mRNA levels and plasma concentrations of three liver-secreted proteins.
OBJECTIVE
Ornithine alpha-ketoglutarate (OKG) displays anabolic properties at the hepatic level, but the mechanisms involved remain unclear. This study investigated in vivo the ability of OKG to modulate hepatic gene expression of three liver-secreted proteins: albumin, transthyretin, and retinol binding protein.


METHODS
One hundred eighty rats were fed for 5 d with a balanced regimen enriched with OKG (5 g.kg(-1).d(-1)) or an isonitrogenous mixture (alanine, glycine, and serine). Hepatic mRNA levels and plasma concentrations of the three proteins studied were determined at the end of the nutrition period and after 1, 2, and 3 d of food deprivation. Results were compared by analysis of variance and Bonferroni-Dunn tests.


RESULTS
At the end of the nutrition period, hepatic mRNA levels and plasma concentrations of the three proteins were not modified by OKG supplementation. However, OKG largely increased mRNA levels of albumin, transthyretin, and retinol binding protein on the first day of starvation compared with control animals (+68%, +64% and +51%, respectively; P < 0.01 versus control). OKG precociously increased albuminemia (on day 2) but had no effect on plasma concentrations of transthyretin and retinol binding protein. Neither regulation of polyamine hepatic concentration nor alteration in hepatic amino acid content seemed to be implicated in these actions.


CONCLUSIONS
This study is the first to demonstrate that OKG regulates in vivo liver gene expression during acute malnutrition by modulating hepatic mRNA levels.
Segaud
Frédéric
F
Laboratoire de Biologie de la Nutrition EA 2498, Faculté de Pharmacie, Paris, France. frederic.segaud@nutrition-paris5.org
Lardeux
Bernard
B
Alexandre-Gouabau
Marie-Cécile
MC
Bleiberg-Daniel
Fanny
F
Nakib
Samir
S
Cynober
Luc
L
Moinard
Christophe
C
D000418:Albumins / Q000235:genetics / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009952:Ornithine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011228:Prealbumin / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012177:Retinol-Binding Proteins / Q000235:genetics / Q000378:metabolism; D054839:Retinol-Binding Proteins, Plasma; D013217:Starvation / Q000378:metabolism*
D000418:Albumins; D011228:Prealbumin; D012333:RNA, Messenger; D012177:Retinol-Binding Proteins; D054839:Retinol-Binding Proteins, Plasma; C002118:ornithine alpha-ketoglutarate; D009952:Ornithine