Title: Long-chain n-3 fatty acids enhance neonatal insulin-regulated protein metabolism in piglets by differentially altering muscle lipid composition Authors
|Bergeron, Karen - INSTI NUTRACEUTICALS &|
|Julien, Pierre - LIPID RESEARCH CENTER|
|Myre, Alexandre - INSTI NUTRACEUTICALS &|
|Thivierge, M. Carole - ROWETT RESEARCH INSTI|
Submitted to: Journal of Lipid Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: August 2, 2007
Publication Date: November 1, 2007
Citation: Bergeron, K., Julien, P., Davis, T.A., Myre, A., Thivierge, M.C. 2007. Long-chain n-3 fatty acids enhance neonatal insulin-regulated protein metabolism in piglets by differentially altering muscle lipid composition. Journal of Lipid Research. 48:2396-2410. Interpretive Summary: The ability of muscle to use dietary amino acids to build or renew muscle proteins decreases 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 feeding a milk formula containing either fatty acids from fish oil vs. a control oil mixture in piglets were studied. The results show that feeding a formula containing fatty acids from fish oil blunted the decline in the ability of muscle to respond to insulin. The consumption of fatty acids from fish oil also decreased the oxidation of amino acids, and thus decreased the loss of amino acids from the body. 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.
Technical Abstract: This study investigated the role of long-chain n-3 polyunsaturated fatty acids (LCn-3PUFAs) of muscle phospholipids in the regulation of neonatal metabolism. Twenty-eight piglets were weaned at 2 days of age and raised on one of two milk formulas that consisted of either a control formula supplying 0% or a formula containing 3.5% LCn-3PUFAs until 10 or 28 days of age. There was a developmental decline in the insulin sensitivity of amino acid disposal in control pigs during the first month of life, with a slope of -2.24 micromol.kg(-1).h(-1) (P = 0.01) per unit of insulin increment, as assessed using hyperinsulinemic-euglycemic-euaminoacidemic clamps. LCn-3PUFA feeding blunted this developmental decline, resulting in differing insulin sensitivities (P < 0.001). When protein metabolism was assessed under parenteral feeding-induced hyperinsulinemia, LCn-3PUFAs reduced by 16% whole body oxidative losses of amino acids (from 238 to 231 micromol.kg(-1).h(-1); P = 0.06), allowing 41% more amino acids to accrete into body proteins (from 90 to 127 micromol.kg(-1).h(-1); P = 0.06). The fractional synthetic rate of muscle mixed proteins remained unaltered by the LCn-3PUFA feeding. However, LCn-3PUFAs retarded a developmental increase in the essential-to-nonessential amino acid ratio of the muscle intracellular free pool (P = 0.05). Overall, alterations in metabolism were concomitant with a preferential incorporation of LCn-3PUFAs into muscle total membrane phospholipids (P < 0.001), in contrast to intramuscular triglycerides. These results underscore the potential role of LCn-3PUFAs as regulators of different aspects of protein metabolism in the neonate.