Metabolic endotoxemia is dictated by the type of lipopolysaccharide

Abstract

Lipopolysaccharides (LPS) can promote metabolic endotoxemia, which is considered inflammatory and metabolically detrimental based on Toll-like receptor (TLR)4 agonists such as Escherichia coli-derived LPS. LPS from certain bacteria antagonize TLR4 yet contribute to endotoxemia measured by Endotoxin Units (EU). We found that E. coli LPS impaired gut barrier function and worsened glycemic control in mice, but equal doses of LPS from other bacteria did not. Matching the LPS dose from R. sphaeroides and E. coli by EU revealed that only E. coli LPS promoted dysglycemia, adipose inflammation, delayed intestinal glucose absorption, and augmented insulin and GLP-1 secretion. Metabolically beneficial endotoxemia promoted by R. sphaeroides LPS counteracted dysglycemia caused by an equal dose of E. coli LPS and promoted insulin sensitivity in obese mice. The concept of metabolic endotoxemia should be expanded beyond LPS load (EU) to include LPS characteristics, where the balance of deleterious and beneficial endotoxemia regulates host metabolism. HighlightsO_LIType of LPS dictates gut barrier function, inflammation, insulin, GLP-1, intestinal glucose absorption and blood glucose C_LIO_LIEndotoxin Units (EU) do not reflect how LPS influences blood glucose or hormones C_LIO_LILPS derived from certain types of bacteria are insulin sensitizers C_LIO_LIR. sphaeroides LPS promotes metabolically beneficial endotoxemia C_LIO_LILPS characteristics dictate metabolically beneficial versus deleterious endotoxemia C_LI