Hypercortisolemia alters muscle protein anabolism following ingestion of essential amino acids

Abstract

Debilitating injury is accompanied by hypercortisolemia, muscle wasting, and disruption of the normal anabolic response to food. We sought to determine whether acute hypercortisolemia alters muscle protein metabolism following ingestion of a potent anabolic stimulus: essential amino acids (EAA). A 27-h infusion (80 μg · kg−1 · h−1) of hydrocortisone sodium succinate mimicked cortisol (C) levels accompanying severe injury (>30 μg/dl), (C + AA; n = 6). The control group (AA) received intravenous saline ( n = 6). Femoral arteriovenous blood samples and muscle biopsies were obtained during a primed (2.0 μmol/kg) constant infusion (0.05 μmol · kg−1 · min−1) ofl-[ ring-2H5]phenylalanine before and after ingestion of 15 g of EAA. Hypercortisolemia [36.5 ± 2.1 (C + AA) vs. 9.0 ± 1.0 μg/dl (AA)] increased postabsorptive arterial, venous, and muscle intracellular phenylalanine concentrations. Hypercortisolemia also increased postabsorptive and post-EAA insulin concentrations. Net protein balance was blunted (40% lower) following EAA ingestion but remained positive for a greater period of time (60 vs. 180 min) in the C + AA group. Thus, although differences in protein metabolism were evident, EAA ingestion improved muscle protein anabolism during acute hypercortisolemia and may help minimize muscle loss following debilitating injury.

Amino acid ingestion improves muscle protein synthesis in the young and elderly

“…2 H5]phenylalanine was added to the EAA drink to maintain the isotopic enrichment (tracer-to-tracee ratio) in the femoral artery at ϳ0.08 (30). The amino acids were dissolved in 250 ml of a noncaloric, noncaffeinated soft drink and consumed as a bolus at 1100.…”

“…It is possible that detecting age-related differences in postabsorptive protein metabolism is beyond the sensitivity limits of current technology. However, after ingestion of amino acids, the supply of the precursor elements necessary to stimulate protein synthesis can increase substantially, albeit transiently (30). Consequently, it is perhaps more likely that any age-related alteration in muscle protein synthesis and/or breakdown will be exaggerated during the period immediately after nutrient ingestion and may therefore be more readily detectable.…”

The Catabolic Effects of Prolonged Inactivity and Acute Hypercortisolemia Are Offset by Dietary Supplementation

“…We have previously demonstrated that EAA supplementation effectively stimulates net muscle protein synthesis acutely (24) and after 28 d of BR (23). Furthermore, as little as 15 g of EAAs can stimulate muscle protein synthesis and maintain net protein balance for more than 90 min in the presence of acute hypercortisolemia (Ͼ30 g⅐dl Ϫ1 ) (25). The goal of the current study was to expand on our previous research and examine the combined effects of prolonged BR and acute hypercortisolemic challenges, a model depicting two common consequences of hospitalization due to trauma or illness.…”

Amino acid repletion does not decrease muscle protein catabolism during hemodialysis

“…Lack of a decrease in protein catabolism, despite an increase in plasma insulin and abundant amino acid supply during HDϩAA, could be due to a concomitant increase in plasma cortisol (37) and proinflammatory cytokine activation (19). Preliminary evidence from our laboratory has shown that IL-6 is released from skeletal muscle (41) and may mediate muscle protein catabolism (42,43).…”

“…Sham HD has been shown to induce muscle protein catabolism even in the absence of amino acid loss (23). Augmented protein catabolism that is uncorrected by amino acid infusion could be due to concomitant increase in plasma cortisol (37) and cytokine activation (19,44); both are known to induce protein catabolism. Similar changes in protein kinetics are observed in other stress states (4,16).…”