Metabolic endotoxemia is dictated by the type of lipopolysaccharide
Fernando F. Anhê,
Nicole G. Barra,
Joseph F. Cavallari,
Brandyn D. Henriksbo,
Jonathan D. Schertzer
Affiliations
Fernando F. Anhê
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
Nicole G. Barra
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
Joseph F. Cavallari
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
Brandyn D. Henriksbo
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
Jonathan D. Schertzer
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; Corresponding author
Summary: 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.
