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-C6 and N
phenylalanine isotopes. In parallel, whole-body
lipid and
carbohydrate kinetics were assessed using constant infusions of [U-C6]
palmitate, [6,6-H2]
glucose, and [H5]
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.