Endotoxin biomarkers are associated with adiposity and cardiometabolic risk across 6 years of follow-up in youth

Context Metabolic endotoxemia may be a shared mechanism underlying childhood obesity and early-onset metabolic diseases (e.g., type 2 diabetes, non-alcoholic fatty liver disease). Objective Examine prospective associations of serum endotoxin biomarkers lipopolysaccharide (LPS) and its binding protein, LPS binding protein (LBP), and anti-endotoxin core IgG (EndoCabIgG) with adiposity and cardiometabolic risk in youth. Design/setting This prospective study included 393 youth in the EPOCH cohort in Colorado. Participants were recruited 2006-2009 at age 10 y (baseline) and followed for six years (follow-up). We examined associations of endotoxin biomarkers at baseline with adiposity (BMI z-score, VAT, SAT, skinfolds, waist circumference) and cardiometabolic risk (insulin, glucose, adipokines, lipid profile, blood pressure) across both visits using mixed-effects regression, and with hepatic fat fraction (HFF) at follow-up using linear regression. Results Higher LPS and LBP predicted greater adiposity across follow-up. Each 1-unit ln-transformed LPS corresponded with 0.23 (95% CI: 0.03, 0.43) units BMI z-score, 5.66 (1.99, 9.33) mm (3) VAT, 30.7 (8.0, 53.3) mm (3) SAT, and 8.26 (4.13, 12.40) mm skinfold sum. EndoCabIgG was associated with VAT only (3.03 [0.34, 5.71] mm (3)). LPS was associated with higher insulin (1.93 [0.08, 3.70] mu U/mL) and leptin (2.28 [0.66, 3.90] ng/mL), and an adverse lipid profile. No association was observed with HFF. Accounting for pubertal status and lifestyle behaviors did not change findings. However, adjustment for pre-pregnancy BMI and gestational diabetes attenuated most associations. Conclusions Serum endotoxin may be a marker of pathophysiological processes underlying development of childhood obesity and cardiometabolic conditions associated with exposure to fetal overnutrition.

Automated summary

Serum endotoxin may be a marker of pathophysiological processes underlying the development of childhood obesity and cardiometabolic conditions associated with exposure to fetal overnutrition.