NUTRITIONAL REGULATION OF CELL AND ORGAN GROWTH, DIFFERENTIATION, AND DEVELOPMENT
Location: Children Nutrition Research Center (Houston, Tx)
Title: Long-chain omega-3 fatty acids regulate bovine whole-body protein metabolism by promoting muscle insulin signalling to the Akt-mTOR-S6K1 pathway and insulin sensitivity.
| Gingras, Andree-Anne - LAVAL UNIVERSITY |
| White, Phillip - LAVAL UNIVERSITY |
| Chouinard, P. Yvan - LAVAL UNIVERSITY |
| Julien, Pierre - LAVAL UNIV HOSPITAL CTR |
| Dombrowski, Luce - LAVAL UNIVERSITY |
| Couture, Yvon - UNIVERSITE DE MONTREAL |
| Dubreuil, Pascal - UNIVERSITE DE MONTREAL |
| Myre, Alexandre - LAVAL UNIVERSITY |
| Bergeron, Karen - LAVAL UNIVERSITY |
Submitted to: Journal of Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: November 28, 2006
Publication Date: December 7, 2006
Citation: Gingras, A-A., White, P.J., Chouinard, P.Y., Julien, P., Davis, T.A., Dombrowski, L., Couture, Y., Dubreuil, P., Myre, A., Bergeron, K., Marette, A., Thivierge, M.C. 2007. Long-chain omega-3 fatty acids regulate bovine whole-body protein metabolism by promoting muscle insulin signalling to the Akt-mTOR-S6K1 pathway and insulin sensitivity. Journal of Physiology. 579(Pt 1):269-284.
Interpretive Summary: The ability of muscle to use dietary amino acids to build or renew muscle proteins is gradually lost with age. This is partly due to a decline in the ability of muscle to respond to the hormone insulin. Insulin is a hormone that rises in response to eating and induces an increase in the synthesis of muscle proteins and a decrease in the breakdown of muscle proteins. Since the fatty acids from fish oil are known to improve the response of glucose metabolism to insulin in insulin-resistant states like diabetes, the potential of fatty acids from fish oil to regulate the response of protein metabolism to insulin was investigated in this study. The effects of 5 weeks of feeding fatty acids from fish oil vs. a control oil mixture in growing steers were studied. The consumption of fatty acids from fish oil decreased the oxidation of amino acids, and thus decreased the loss of amino acids from the body. Fish oil fatty acids also increased the ability of insulin to stimulate the body to use dietary amino acids to build body protein. This response to fish oil fatty acids was due to an increase in the activation of the intracellular signaling pathway in skeletal muscle that regulates the synthesis of muscle proteins. We conclude that chronic feeding of fatty acids from fish oil is a novel nutritional therapy that can enhance the ability of insulin to stimulate the building and renewal of muscle protein.
The ability of the skeletal musculature to use amino acids to build or renew constitutive proteins is gradually lost with age and this is partly due to a decline in skeletal muscle insulin sensitivity. Since long-chain omega-3 polyunsaturated fatty acids (LC"n"-3PUFA) from fish oil are known to improve insulin-mediated glucose metabolism in insulin-resistant states, their potential role in regulating insulin-mediated protein metabolism was investigated in this study. Experimental data are based on a switchback design composed of three 5-week experimental periods using six growing steers to compare the effect of a continuous abomasal infusion of LC"n"-3PUFA-rich menhaden oil with an iso-energetic control oil mixture. Clamp and insulin signalling observations were combined with additional data from a second cohort of six steers. We found that enteral LC"n"-3PUFA potentiate insulin action by increasing the insulin-stimulated whole-body disposal of amino acids from 152 to 308 micromol kg[-1] h[-1] (P=0.006). The study further showed that in the fed steady-state, chronic adaptation to LC"n"-3PUFA induces greater activation ("P"<0.05) of the Akt-mTOR-S6K1 signalling pathway. Simultaneously, whole-body total flux of phenylalanine was reduced from 87 to 67 micromol kg[-1] h[-1] ("P"=0.04) and oxidative metabolism was decreased ("P"=0.05). We conclude that chronic feeding of menhaden oil provides a novel nutritional mean to enhance insulin-sensitive aspects of protein metabolism.