1. Microbiota-Produced -Formyl Peptide fMLF Promotes Obesity-Induced Glucose Intolerance.
- Author
-
Wollam, Joshua, Riopel, Matthew, Yong-Jiang Xu, Johnson, Andrew M. F., Ofrecio, Jachelle M., Wei Ying, El Ouarrat, Dalila, Chan, Luisa S., Han, Andrew W., Mahmood, Nadir A., Ryan, Caitlin N., Yun Sok Lee, Watrous, Jeramie D., Chordia, Mahendra D., Pan, Dongfeng, Jain, Mohit, Olefsky, Jerrold M., Xu, Yong-Jiang, Ying, Wei, and Lee, Yun Sok
- Subjects
GLUCOSE intolerance ,GLUCAGON-like peptide 1 ,ENTEROENDOCRINE cells ,GUT microbiome ,PEPTIDE receptors ,METABOLIC disorders ,ANIMAL experimentation ,CELL culture ,CELL physiology ,COMPARATIVE studies ,ANIMAL nutrition ,ENZYME-linked immunosorbent assay ,FLOW cytometry ,GLUCOSE ,INSULIN ,LIQUID chromatography ,MASS spectrometry ,RESEARCH methodology ,MEDICAL cooperation ,MICE ,OBESITY ,OLIGOPEPTIDES ,RESEARCH ,FLUORESCENCE in situ hybridization ,EVALUATION research - Abstract
The composition of the gastrointestinal microbiota and associated metabolites changes dramatically with diet and the development of obesity. Although many correlations have been described, specific mechanistic links between these changes and glucose homeostasis remain to be defined. Here we show that blood and intestinal levels of the microbiota-produced N-formyl peptide, formyl-methionyl-leucyl-phenylalanine, are elevated in high-fat diet-induced obese mice. Genetic or pharmacological inhibition of the N-formyl peptide receptor Fpr1 leads to increased insulin levels and improved glucose tolerance, dependent upon glucagon-like peptide 1. Obese Fpr1 knockout mice also display an altered microbiome, exemplifying the dynamic relationship between host metabolism and microbiota. Overall, we describe a new mechanism by which the gut microbiota can modulate glucose metabolism, providing a potential approach for the treatment of metabolic disease. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF