Metabolic endotoxaemia in childhood obesity

Abstract

Background: Childhood obesity is associated with chronic low-grade inflammation considered as a precursor to metabolic disease; however, the underlying mechanisms for this remain unclear. Studies in adults have implicated gut derived gram-negative bacterial fragments known as lipopolysaccharide or endotoxin, activating the inflammatory response, whilst the importance in childhood obesity is unclear. The aim of this research is to understand the relationship between circulating endotoxin in childhood obesity, and its' association with inflammatory and cardiovascular (CV) injury biomarkers.

Methods: Fasted blood was obtained from children with varying degrees of obesity (age: 13.9 ± 2.3Yr; BMI: 35.1 ± 5.2 Kg/m(2); n = 60). Multiplex CVD biomarker immunoassays were used to determine systemic levels of inflammatory and vascular injury biomarkers, such as tumour necrosis factor-α (TNF-α), interleukin (IL-) 1β, 6, 8 and 10, plasminogen activator inhibitor-1 (PAI-1), soluble intercellular adhesion molecule type-1 (sICAM-1), matrix metalloproteinase-9 (MMP-9), myeloperoxidase (MPO) and vascular endothelial growth factor (VEGF) as well as endotoxin levels.

Results: Endotoxin levels demonstrated a significant and positive correlation with the markers for inflammation, vascular injury and atherogenesis (TNF-α: r(2) = 0.077, p < 0.05; PAI-1: r(2) = 0.215, p < 0.01; sICAM-1: r(2) = 0.159, p < 0.01; MMP-9: r(2) = 0.159, p < 0.01; MPO: r(2) = 0.07, p < 0.05; VEGF: r(2) = 0.161, p < 0.01). Males demonstrated significantly higher circulating endotoxin than females (Males: 9.63 ± 5.34 EU/ml; p = 0.004; Females: 5.56 ± 4.06 EU/ml; n = 60) in these BMI and age-matched cohorts.

Conclusion: The present study demonstrates for the first time a significant association between circulating endotoxin and biomarkers of metabolic risk in children as young as 11 years. Thus, endotoxin-mediated sub-clinical inflammation during childhood obesity may be a key contributor to T2DM and CVD development later in life.

Keywords: Cardiovascular injury markers; Childhood obesity; Endotoxin; Insulin resistance.

Fig. 1

Correlation between log endotoxin (EU/ml) levels and the inflammatory markers: (a) log TNF-α pg/ml (p < 0.05) (b) log MCP-1 ng/ml (p < 0.01), in BMI and age-matched children and adolescents

Fig. 2

Correlation between log endotoxin (EU/ml) levels and the following markers of CVD: (a) log PAI-1 (ng/ml) (p < 0.05), (b) log sICAM-1 (ng/ml) (p < 0.05), (c) log MMP-9 (pg/ml) (p < 0.05), (d) log MPO (pg/ml) (p < 0.05), (e) log VEGF (pg/ml) (p < 0.05) and (f) log eSelectin (X/ml) (p < 0.05) in BMI and age-matched children and adolescents

Fig. 3

Correlation between log endotoxin (EU/ml) levels and (a) systolic blood pressure (mm Hg) (n = 37) and (b) diastolic blood pressure (mm Hg) (n = 51) in BMI and age-matched children and adolescents

Fig. 4

Comparison of the mean relative endotoxin serum concentrations (EU/ml) ± SEM in male and female BMI and age-matched children and adolescents