Lipopolysaccharide-binding protein (LBP) serum levels in children with OSA and obesity

Abstract

Obstructive sleep apnea (OSA) has been linked to obesity and the metabolic syndrome (MetS). All these conditions are further tightly linked to inflammation, the origin of the latter still being under debate. In recent years, the gut microbiota and/or gut permeability have emerged as important factors in the vicious cycle of obesity, MetS and inflammation. The gut microbiota, which serves as reservoir for bacterial lipopolysaccharides (LPS), could be altered by OSA and trigger inflammation. Lipopolysaccharide-binding protein (LBP) is a 65-kDa acute-phase protein derived from the liver which has been viewed as a surrogate marker of underlying low level endotoxemia brought about by LPS from the gut. We hypothesized that systemic LBP levels would be higher in obese children and in those with OSA. Consecutive snoring and non-snoring children (mean age: 6.8 ± 1.3 years) were included after they underwent overnight polysomnographic evaluation and a fasting blood sample was drawn the morning after the sleep study. Children were subidivided into 4 sub-groups based on the presence of obesity (BMI z score > 1.65) or OSA (obstructive AHI > 2/hrTST). Plasma LBP levels were assayed using commercial ELISA kits. Of the children studied to date ( n = 56), non-obese controls had lowest levels of LBP, and the presence of obesity without OSA was associated with significant increases in LBP levels ( p < 0.03). Non-obese children with OSA exhibited LBP leves that were similar to those of obese children without OSA ( p < 0.01 vs. non-obese without OSA), with obese children with OSA demonstrating the highest LBP levels of all 4 groups ( p < 0.02 vs. all 3 other groups). Systemic low level endotoxemia and resultant systemic inflammation is present in children who are either obese or suffer from OSA, and is particularly prominent when both conditions are present. We postulate that altered sleep and other factors facilitating obesity such as high fat diet may disrupt the gut microbiome, and lead to increased systemic LPS leaks with resultant inflammation. NIH HL65270.