Microbiota-Produced N -Formyl Peptide fMLF Promotes Obesity-Induced Glucose Intolerance.

Autor:	Wollam J; Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, La Jolla, CA., Riopel M; Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, La Jolla, CA., Xu YJ; Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, La Jolla, CA.; Department of Pharmacology, University of California, San Diego, La Jolla, CA., Johnson AMF; Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, La Jolla, CA., Ofrecio JM; Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, La Jolla, CA., Ying W; Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, La Jolla, CA., El Ouarrat D; Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, La Jolla, CA., Chan LS; Second Genome, Inc., South San Francisco, CA., Han AW; Second Genome, Inc., South San Francisco, CA., Mahmood NA; Second Genome, Inc., South San Francisco, CA., Ryan CN; Second Genome, Inc., South San Francisco, CA., Lee YS; Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, La Jolla, CA., Watrous JD; Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, La Jolla, CA.; Department of Pharmacology, University of California, San Diego, La Jolla, CA., Chordia MD; Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA., Pan D; Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA., Jain M; Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, La Jolla, CA.; Department of Pharmacology, University of California, San Diego, La Jolla, CA., Olefsky JM; Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, La Jolla, CA jolefsky@ucsd.edu.
Jazyk:	angličtina
Zdroj:	Diabetes [Diabetes] 2019 Jul; Vol. 68 (7), pp. 1415-1426. Date of Electronic Publication: 2019 Apr 22.
DOI:	10.2337/db18-1307
Abstrakt:	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. (© 2019 by the American Diabetes Association.)
Databáze:	MEDLINE
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