Intravenous administration of amino acids during anesthesia stimulates muscle protein synthesis and heat accumulation in the body

1 Division of Pharmacology, Drug Safety and Metabolism, Otsuka Pharmaceutical Factory, Naruto, Tokushima; and 2 Department of Animal Science, Utsunomiya University, Utsunomiya, Tochigi, Japan Submitted 22 July 2005 ; accepted in final form 5 December 2005 The present study was conducted to determine the contribution of muscle protein synthesis to the prevention of anesthesia-induced hypothermia by intravenous administration of an amino acid (AA) mixture. We examined the changes of intraperitoneal temperature (Tcore) and the rates of protein synthesis ( K s ) and the phosphorylation states of translation initiation regulators and their upstream signaling components in skeletal muscle in conscious (Nor) or propofol-anesthetized (Ane) rats after a 3-h intravenous administration of a balanced AA mixture or saline (Sal). Compared with Sal administration, the AA mixture administration markedly attenuated the decrease in Tcore in rats during anesthesia, whereas Tcore in the Nor-AA group became slightly elevated during treatment. Stimulation of muscle protein synthesis resulting from AA administration was observed in each case, although K s remained lower in the Ane-AA group than in the Nor-Sal group. AA administration during anesthesia significantly increased insulin concentrations to levels 6-fold greater than in the Nor-AA group and enhanced phosphorylation of eukaryotic initiation factor 4E-binding protein-1 (4E-BP1) and ribosomal protein S6 protein kinase relative to all other groups and treatments. The alterations in the Ane-AA group were accompanied by hyperphosphorylation of protein kinase B and the mammalian target of rapamycin (mTOR). These results suggest that administration of an AA mixture during anesthesia stimulates muscle protein synthesis via insulin-mTOR-dependent activation of translation initiation regulators caused by markedly elevated insulin and, thereby, facilitates thermal accumulation in the body. thermogenesis; translation initiation; insulin; hypothermia Address for reprint requests and other correspondence: Ippei Yamaoka, Naruto, Tokushima 772–8601, Japan (e-mail: yamaokih{at}otsukakj.co.jp )