Serum sterol profiling reveals increased cholesterol biosynthesis in childhood obesity

Quantitative sterol profiling in obese children and their clinical implications have not been fully investigated. The aim of study was to evaluate the metabolic changes in serum cholesterol and its precursors and metabolites, and their associations with clinical characteristics of childhood obesity. A total of 253 children aged 6-14 years (72 obese, 39 overweight, and 72 normal controls; 147 girls and 106 boys) were recruited. Anthropometric indices, body composition, and fasting total lipid profiles were determined. Serum concentrations of 20 sterols, as their free fraction, were analyzed through gas chromatography-mass spectrometry-based metabolite profiling. There were no significant differences in total- and LDL-cholesterols between groups. Serum levels of the main cholesterol precursors, lanosterol (P<0.02) and lathosterol (P<0.0001), were significantly higher in obese children. In addition, they showed positive correlations with waist to hip ratio, body fat percent, and body fat mass. The metabolic ratios of lanosterol and lathosterol to cholesterol were also elevated (P<0.01 both), indicating the up-regulation of cholesterol biosynthesis with childhood obesity. In contrast, the absorption of plant sterols tended to show a compensatory decrease in obese children. Strong correlations between free cholesterol and total- and LDL-cholesterols were observed (r>0.760, P<0.001), while there was no correlation with HDL-cholesterols. The levels of total cholesteryl ester were closely associated with triglyceride (r=0.763, P<0.001). Quantitative results indicate that childhood obesity may increase cholesterol synthesis while maintaining overall cholesterol homeostasis.