The nutrient content of and feeding recommendations for milk replacers (MR) vary widely in North America, and acceleration of growth through manipulation of protein and energy intakes can reduce rearing costs of dairy operations. The effects of varying the protein and energy intake of MR on metabolite concentrations in plasma, liver, and muscle and the phosphorylation activity of protein kinase B (AKT) and ribosomal protein S6 (rpS6) cell signals in liver and muscle were assessed. Twenty-four newborn Holstein calves were fed 1 of 4 MR for 9 wk (n=6/treatment): (1) a 20% crude protein (CP), 20% fat MR fed at 441 g of dry matter (DM)/d (CON); (2) a high-protein, medium-fat MR (HPMF; 28% CP, 20% fat) fed at 951 g of DM/d; (3) a high-protein, high-fat MR (HPHF; 27% CP, 28% fat) fed at 951 g of DM/d; and (4) HPHF fed at 1,431 g of DM/d (HPHF+). Water and starter (20% CP, 1.43% fat) were offered ad libitum and calves were fed MR twice daily. Plasma samples were obtained at 1, 5, and 9 wk of age. Calves were not weaned and were slaughtered after the last blood sampling. Liver and muscle tissues were collected and analyzed for metabolite concentrations and cell signaling activity. Calves fed all treatments had lower plasma concentrations of Phe and Tyr, and a trend for lower Leu, but greater concentrations of Thr relative to calves fed CON. Calves fed all treatments had increased muscle concentrations of Met and muscle to plasma ratios of Phe, Tyr, and branched-chain amino acids compared with CON. All treatments increased liver to plasma ratios of Phe and Tyr but diminished the ratios of Met compared with CON. Phosphorylation of protein kinase B was not affected by treatment; however, relative to calves fed HPHF, HPMF and HPHF+ diets increased phosphorylation ratios of ribosomal protein S6 in the liver. Therefore, the changes in plasma and tissue concentrations and plasma to tissue ratios of amino acids were associated with enhanced growth rates. However, cell signaling activity was not consistent with accelerated growth in calves fed treatments with increased contents of energy and protein possibly due to confounding effects of diet (MR + starter) or fasting before tissue harvesting. Muscle concentrations of Met might have a regulatory role in protein synthesis in rapidly growing calves fed high levels of CP and energy.
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