Metabolic endotoxemia is dictated by the type of lipopolysaccharide

Fernando F Anhê; Nicole G Barra; Joseph F Cavallari; Brandyn D Henriksbo; Jonathan D Schertzer

doi:10.1016/j.celrep.2021.109691

Metabolic endotoxemia is dictated by the type of lipopolysaccharide

Cell Rep. 2021 Sep 14;36(11):109691. doi: 10.1016/j.celrep.2021.109691.

Authors

Fernando F Anhê¹, Nicole G Barra¹, Joseph F Cavallari¹, Brandyn D Henriksbo¹, Jonathan D Schertzer²

Affiliations

¹ Department of Biochemistry and Biomedical Sciences, McMaster University, 1200 Main Street W., Hamilton, ON L8N 3Z5, Canada; Farncombe Family Digestive Health Research Institute, McMaster University, 1200 Main Street W., Hamilton, ON L8N 3Z5, Canada; Centre for Metabolism, Obesity and Diabetes Research, McMaster University, 1200 Main Street W., Hamilton, ON L8N 3Z5, Canada.
² Department of Biochemistry and Biomedical Sciences, McMaster University, 1200 Main Street W., Hamilton, ON L8N 3Z5, Canada; Farncombe Family Digestive Health Research Institute, McMaster University, 1200 Main Street W., Hamilton, ON L8N 3Z5, Canada; Centre for Metabolism, Obesity and Diabetes Research, McMaster University, 1200 Main Street W., Hamilton, ON L8N 3Z5, Canada. Electronic address: schertze@mcmaster.ca.

PMID: 34525353
DOI: 10.1016/j.celrep.2021.109691

Abstract

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.

Keywords: diabetes; immunometabolism; inflammation; microbiome; microbiota; obesity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adipose Tissue / drug effects
Adipose Tissue / metabolism
Adipose Tissue / pathology
Animals
Blood Glucose / analysis
Body Weight / drug effects
Endotoxemia / etiology*
Endotoxemia / metabolism
Escherichia coli / metabolism
Glucagon-Like Peptide 1 / blood
Glucose / metabolism
Insulin / blood
Intestines / drug effects*
Intestines / metabolism
Lipopolysaccharides / pharmacology*
Male
Mice
Mice, Inbred C57BL
Mice, Obese
Obesity / metabolism
Obesity / pathology
Peptidoglycan / pharmacology
Rhodobacter sphaeroides / metabolism
Toll-Like Receptor 4 / agonists
Toll-Like Receptor 4 / metabolism

Substances

Blood Glucose
Insulin
Lipopolysaccharides
Peptidoglycan
Toll-Like Receptor 4
Glucagon-Like Peptide 1
Glucose

Grants and funding

FDN-154295/CIHR/Canada