Reduction in mitochondrial biogenesis balanced by a shift away from fat metabolism in critically ill patients

Background In severe sepsis, early mitochondrial dysfunction in skeletal muscle is associated with decreased biogenesis and adverse patient outcome. We hypothesised that reduction in mitochondrial content during critical illness would be balanced by improved efficiency by switching from fatty acid oxidation as metabolic substrate. Methods 30 critically ill patients (70% male, age 56.4±19.7 years, APACHE II score 22.4±6.6) were recruited <24 hours after intensive care admission. Vastus lateralis muscle biopsies were taken on day 1 and 7. Concentrations of mitochondrial respiratory complex proteins and key proteins of the β-oxidation pathway were determined. Mitochondrial DNA content (mtDNA) and PGC1-α mRNA concentrations were determined contemporaneously by RT-qPCR. Muscle and blood metabolic profiles were quantified by H1 nuclear magnetic resonance (H1 NMR). Results There was reduction in both mtDNA (p = 0.003) and PGC1-α (p=0.041) from day 1 to day 7. Mitochondrial respiratory complex I-V concentrations did not change significantly but mitochondrial β-oxidation pathway proteins (CPT1, MCAD, ETF, DecR1) all significantly decreased. There was a significant increase in serum LDL and VLDL from day 1 to day 7 (p<0.01) and intramyocellular concentrations of lipid also increased significantly (p= 0.002). Conclusion These data suggest decreased mitochondrial biogenesis over the first week of critical illness. The decrease in β-oxidation proteins combined with an increase in both serum and muscle fat concentrations suggest a shift away from inefficient fat metabolism during the first 7 days of critical illness. These data have implications for feeding regimes in critical illness.