The Type of Bacterial Lipopolysaccharides Dictates Insulin Resistance, GLP-1 and Insulin Secretion During Metabolic Endotoxemia

Lipopolysaccharides (LPS) can promote metabolic endotoxemia, which is usually modelled using Escherichia coli derived LPS, a potent Toll-like receptor (TLR)4 agonist. LPS from other bacteria can antagonize TLR4 and still contribute to Endotoxin Units (EU). We found that LPS from E. coli impaired glycemic control in mice, whereas equal doses of LPS (up to 0.4 mg/kg) from Salmonella minnesota, Porphyromonas gingivalis and Rhodobacter sphaeroides did not alter blood glucose. Matching the LPS dose from R. sphaeroides and E. coli defined in EU (0.9x106 EU/kg) revealed that only E. coli LPS promoted dysglycemia and augmented glucose-stimulated insulin and GLP-1 secretion in mice. R. sphaeroides LPS antagonized dysglycemia caused by an equal dose (0.2 mg/kg) of E. coli LPS. Acute and chronic delivery of R. sphaeroides LPS improved insulin sensitivity in obese mice. We propose that the concept of metabolic endotoxemia should be expanded beyond LPS load (EU) to include LPS characteristics.