Burn injury results in increased cholesterol synthesis

Abstract

The decrease in plasma cholesterol after major trauma including burn injury has been associated with negative outcomes. In burn injury, decreased cholesterol synthesis has been speculated as the cause of decreased plasma cholesterol. This study directly tests the hypothesis that burn injury leads to decreased cholesterol synthesis. Burn injury was administered (15% total body surface area immersed in water at 90°C for 5 seconds). Both sham (n=6) and burn (n=6) animals received an ip bolus of 2H2O 1 day post burn, targeting 2% 2H2O plasma enrichment. Drinking water was enriched at 3% 2H2O. Blood samples were collected at various times, up to 8 days post burn. Cholesterol was isolated from plasma and derivatized. Mass isotopomer distribution was determined by gas chromatography-mass spectrometry. Isotopomer Spectral Analysis was used to estimate cholesterol synthesis parameters with the number of exchangeable H/D atoms = 25. We found no decrease in plasma cholesterol level with burn injury in this mouse model over 8 days post burn. Cholesterol synthesis was calculated as the product of the fraction of new synthesis and the plasma cholesterol concentration. We found higher cholesterol synthesis in burned mice than sham at each post burn day 4–8. For example, at day 7, cholesterol synthesis was 1.94 mM for burned mice compared to 1.08 for sham mice. Thus, burned mice respond to injury by increasing cholesterol synthesis. (supported by NIH P50GM0217001).