Maternal obesity is associated with higher levels of metabolic endotoxemia markers in the maternal and neonatal serum

Background:

Obesity, diabetes and inflammation have long been associated, but the cause of the inflammation is unknown. One hypothesis is that bacterial products, such as lipopolysaccharides (LPS) are translocated across the gut in association with a high-fat diet which drives inflammation, a condition termed metabolic endotoxemia (ME). Data have shown that an increase in serum LPS and reduced levels of endotoxin-core IgM (endoCAb IgM) antibodies are associated with both obesity and diabetes. In this study we sought to determine if changes in serum LPS and endoCAb IgM are associated with maternal obesity and diabetes and if the fetus is exposed to these markers of ME. We also tested whether markers of inflammation (GLP-2 (glucagon-like peptide 2), IL-6) were increased with maternal obesity and if these markers were observed in the neonate.

Methods:

Commercially available ELISA assays were utilized to measure LPS, GLP-2 and EndoCAb IgM levels in matched maternal and neonatal (cord blood) serum samples (N = 146). The Milliplex system was used to measure IL-6 through our core facility.

Results:

While we did not find any significant change in LPS levels in either maternal or neonatal samples, we found that endoCAb IgM showed a tendency towards lower levels in neonates of obese women, compared to non-obese individuals (p= 0.056). When stratifying by gestational weight gain category, we found GLP-2 to be significantly higher in mothers with an excessive weight gain, compared to normal weight gain (p= 0.014). Further we found that GLP-2 is significantly higher in obese and obese-diabetic mothers when compared to the control. Moreover a significant correlation between maternal and neonatal IL-6 levels was observed (p= 0.035).

Conclusions:

While we did not find significant changes in LPS levels in the mother or neonate, the finding of altered endotoxin IgM levels is of interest. Because IgM antibodies do not cross the placenta, the endoCAb IgM detected in neonatal serum is likely due to the fetal immune response to circulating LPS levels. Correlation of maternal and neonatal IL-6 may similarly point to fetal exposure to markers of maternal ME during gestation. Higher levels of GLP-2 in obese and obese-diabetic mothers, as well as in mothers with an excessive gestational weight gain are concordant with the known association of GLP-2 with insulin resistance and may also be a response to maternal ME.