Metabolic endotoxemia is dictated by the type of lipopolysaccharide

• Published in: Cell reports (Cambridge) Vol. 36; no. 11; p. 109691
• Main Authors: Anhê, Fernando F., Barra, Nicole G., Cavallari, Joseph F., Henriksbo, Brandyn D., Schertzer, Jonathan D.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 14-09-2021; Elsevier
• Subjects: Adipose Tissue - drug effects; Adipose Tissue - metabolism; Adipose Tissue - pathology; Animals; Blood Glucose - analysis; Body Weight - drug effects; diabetes; Endotoxemia - etiology; Endotoxemia - metabolism; Escherichia coli - metabolism; Glucagon-Like Peptide 1 - blood; Glucose - metabolism; immunometabolism; inflammation; Insulin - blood; Intestines - drug effects; Intestines - metabolism; Lipopolysaccharides - pharmacology; Male; Mice; Mice, Inbred C57BL; Mice, Obese; microbiome; microbiota; obesity; Obesity - metabolism; Obesity - pathology; Peptidoglycan - pharmacology; Rhodobacter sphaeroides - metabolism; Toll-Like Receptor 4 - agonists; Toll-Like Receptor 4 - metabolism; microbiota; immunometabolism; inflammation; diabetes; microbiome; obesity
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2021.109691

Lipopolysaccharides (LPSs) 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. LPSs from certain bacteria antagonize TLR4 yet contribute to endotoxemia measured by endotoxin units (EUs). We found that E. coli LPS impairs gut barrier function and worsens glycemic control in mice, but equal doses of LPSs from other bacteria do not. Matching the LPS dose from R. sphaeroides and E. coli by EUs reveals that only E. coli LPS promotes dysglycemia and adipose inflammation, delays intestinal glucose absorption, and augments insulin and glucagon-like peptide (GLP)-1 secretion. Metabolically beneficial endotoxemia promoted by R. sphaeroides LPS counteracts dysglycemia caused by an equal dose of E. coli LPS and improves glucose control in obese mice. The concept of metabolic endotoxemia should be expanded beyond LPS load to include LPS characteristics, such as lipid A acylation, which dictates the effect of metabolic endotoxemia.
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•Type of LPS dictates barrier function, inflammation, incretins, and blood glucose•Endotoxin units (EUs) do not reflect how LPS influences blood glucose or insulin•R. sphaeroides LPS promotes metabolically beneficial endotoxemia•LPS characteristics dictate metabolically beneficial versus deleterious endotoxemia
Bacterial lipopolysaccharides (LPSs) can cause metabolic endotoxemia and alter host metabolism. Anhê et al. demonstrate that the type of LPS dictates the metabolic outcome of endotoxemia, which can be detrimental or beneficial to host blood glucose.