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Microbiota-Produced N-Formyl Peptide fMLF Promotes Obesity-Induced Glucose Intolerance
- Source :
- Diabetes, vol 68, iss 7, Diabetes
- Publication Year :
- 2019
- Publisher :
- eScholarship, University of California, 2019.
-
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.
- Subjects :
- 0301 basic medicine
Male
Endocrinology, Diabetes and Metabolism
medicine.medical_treatment
Mice, Obese
Peptide
Gut flora
Medical and Health Sciences
Obese
Mass Spectrometry
Oral and gastrointestinal
Mice
0302 clinical medicine
Glucagon-Like Peptide 1
Glucose homeostasis
Insulin
2.1 Biological and endogenous factors
Aetiology
Cells, Cultured
In Situ Hybridization, Fluorescence
In Situ Hybridization
Mice, Knockout
chemistry.chemical_classification
Chromatography
Liquid
Cultured
biology
Chemotaxis
Microbiota
Diabetes
Flow Cytometry
Knockout mouse
Oligopeptides
medicine.medical_specialty
Cells
Knockout
030209 endocrinology & metabolism
Enzyme-Linked Immunosorbent Assay
Carbohydrate metabolism
Diet, High-Fat
Fluorescence
03 medical and health sciences
Endocrinology & Metabolism
Internal medicine
Glucose Intolerance
Internal Medicine
medicine
Animals
Microbiome
Obesity
Metabolic and endocrine
Nutrition
Metabolism
biology.organism_classification
Diet
High-Fat
030104 developmental biology
Endocrinology
Glucose
chemistry
Digestive Diseases
Chromatography, Liquid
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Diabetes, vol 68, iss 7, Diabetes
- Accession number :
- edsair.doi.dedup.....5a8b9e1fc89568ccd641b2356fcbaad3