Endotoxin Biomarkers Are Associated With Adiposity and Cardiometabolic Risk Across 6 Years of Follow-up in Youth

Abstract

Context: Metabolic endotoxemia may be a shared mechanism underlying childhood obesity and early-onset metabolic diseases (eg, type 2 diabetes, nonalcoholic 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 immunoglobulin G (EndoCab IgG) with adiposity and cardiometabolic risk in youth.

Design/setting: This prospective study included 393 youth in the Exploring Perinatal Outcomes Among Children cohort in Colorado. Participants were recruited from 2006 to 2009 at age 10 years (baseline) and followed for 6 years (follow-up). We examined associations of endotoxin biomarkers at baseline with adiposity [body mass index (BMI) z-score, visceral adipose tissue (VAT), subcutaneous adipose tissue (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 log-transformed LPS corresponded with 0.23 (95% CI 0.03, 0.43) units BMI z-score, 5.66 (95% CI 1.99, 9.33) mm3 VAT, 30.7 (95% CI 8.0, 53.3) mm3 SAT, and 8.26 (95% CI 4.13, 12.40) mm skinfold sum. EndoCab IgG was associated with VAT only [3.03 (95% CI 0.34, 5.71) mm3]. LPS was associated with higher insulin [1.93 (95% CI 0.08, 3.70) µU/mL] and leptin [2.28 (95% CI 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 prepregnancy 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.

Keywords: NAFLD; adiposity; cardiometabolic risk; endotoxin; obesity; prospective cohort; type 2 diabetes; youth.