Distinct serum cholesterol and lipoprotein signatures in sepsis and major elective surgery: a lipid-focused NMR study

Background Low circulating cholesterol is a recognised feature of sepsis, but whether the serum lipid signature of sepsis differs from that of sterile (non-infectious) inflammation is unclear. Methods Targeted serum proton nuclear magnetic resonance (NMR) metabolomics (250 metabolites) was used to compare 34 patients with sepsis, 21 patients before and after major elective surgery, and 89 healthy controls. Results Compared with healthy controls, 199 metabolites differed in sepsis and 150 after surgery. 127 changes were common to both states, 23 specific to surgery and 72 to sepsis. Both states lowered total, LDL and HDL cholesterol, cholesteryl esters, phospholipids and several fatty acids. Surgery alone reduced apolipoprotein B, remnant cholesterol and LDL particle number, whereas triglyceride-rich VLDL and the inflammatory marker GlycA were higher in sepsis only. Triglyceride-rich lipoproteins fell after surgery but rose in sepsis, and the sepsis-specific signature was dominated by a coordinated rise across the VLDL subclasses with a fall across the large HDL subclasses. No metabolite distinguished sepsis survivors from non-survivors. Conclusions Low cholesterol was common to both post-operative and septic states, whereas a rise in triglyceride-rich VLDL was detected in sepsis but not after surgery. These exploratory differences require confirmation in matched cohorts, and illustrate how lipid-focused NMR spectroscopy can provide a detailed analysis of cholesterol and lipoprotein signatures in critical illness.