Year: 2019
Type: article
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.
Source: Diabetes
DOI: 10.2337/db18-1307
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
Awards: G1462415530, G1605720030, G2041627414, G2693629440, RapidFire mass spectrometry system, Training Program in Diabetes Research, Mapping the Plasma Exposome and its Association with Human Cardiovascular Disease, G4245978209, INSULIN RECEPTORS AND THE GLUCOSE TRANSPORT SYSTEM, A Gut Microbiome Metabolite Axis in Obesity-Associated Inflammation and Insulin Resistance, Effects of Fractalkine on Beta Cell Function, University of California San Diego Neuroscience Microscopy Imaging Core, Gene Networks controlling macrophage-adipocyte interactions in insulin, G7662487502, Insulin Receptors and the Glucose Transport System, G87692671, Diabetes Research Center (DRC)
OpenAlex ID: W2938699277