Sepsis Increases Muscle Proteolysis in Severely Burned Adults, but Does not Impact Whole-Body Lipid or Carbohydrate Kinetics

Abstract

Sepsis is a common and often fatal consequence of severe burn injury, but its exact effects on whole body and muscle metabolism in the burn patient is unclear. To address this, 13 septic and 11 nonseptic patients (age: 36.9 ± 13.0 years) with burns encompassing >30% of their total body surface area underwent muscle protein kinetic studies under postabsorptive conditions using bolus injections of ring-13C6 and 15N phenylalanine isotopes. In parallel, whole-body lipid and carbohydrate kinetics were assessed using constant infusions of [U-13C6]palmitate, [6,6-2H2]glucose, and [2H5]glycerol, and during a 2-h hyperinsulinemic euglycemic clamp. Muscle mRNA levels of genes implicated in the development of muscle cachexia were assessed by qPCR. Fractional breakdown rates of mixed-muscle proteins were found to be 2.4-fold greater in septic versus nonseptic patients (P < 0.05). No discernable differences in fractional synthetic rate of mixed-muscle proteins or rate of appearance of plasma free fatty acids, glycerol, or glucose could be observed between patient groups, although the latter was significantly associated with burn size (P < 0.05). Hyperinsulinemia stimulated whole-body glucose uptake and suppressed endogenous glucose production and whole-body lipolytic rate to equivalent degrees in both groups. Muscle mRNA levels of genes spanning autophagy, lysosomal, and ubiquitin proteasome-mediated proteolysis were not enhanced in septic versus nonseptic patients. Our results demonstrate that accelerated muscle proteolysis appears to be the principal metabolic consequence of sepsis in severe burn patients and could be a contributing factor to the accelerated loss of muscle mass in these individuals. The exact mechanistic basis for these changes remains unclear.

Cafeteria Diet Impacts the Body Weight and Energy Expenditure of Brown Norway Rats in an Apparent Age Dependent Manner, but Has no Effect on Muscle Anabolic Sensitivity to Nutrition

“…For intracellular free amino acids, ions m/z 336 and 341 were monitored, while for bound protein, ions m/z 237 and 239 were examined. The enrichment of samples with deuterated alanine were examined on a gas-chromatography-pyrolysis-isotope ratio mass spectrometer (Trace 1310 GC coupled to a Delta V IRMS via a high-temperature thermal conversion oven, Thermo Fisher Scientific), respectively, as described previously ( 12 , 13 , 19 ).…”

Astroglia in Sepsis Associated Encephalopathy

“…The neurotransmitter imbalance in the brain is thought to be related to changes in amino acids levels in the blood, in particular a decrease in branched-chain amino acids together with relative increase in aromatic amino acids with consequent increase the presence of the latter in the brain tissue [90]. Excess of the aromatic amino acids in plasma probably results from increased muscle proteolysis [91] and reduced hepatic clearance caused by liver insufficiency in sepsis [92]. Loss of BBB integrity may also contribute to an increased ratio of aromatic/branched chain amino acids in the brain of patients with SAE.…”

Comparison of Arterial-Venous Balance and Tracer Incorporation Methods for Measuring Muscle Fractional Synthesis and Fractional Breakdown Rates

“…25 Moreover, both approaches have shown that altered muscle protein metabolism persist for many months postburn, 26,27 and that the presence of sepsis accelerated muscle catabolism in burn patients. 28,29 Furthermore, both A-V balance and two-bolus approaches both demonstrate that drug therapies, which attenuate muscle catabolism in burned children, do so by stimulating protein synthesis rates. 30,31 In conclusion, the bolus tracer incorporation method and the A-V balance method provide similar values of muscle protein fractional synthesis and breakdown rates.…”