N -acyl taurines are endogenous lipid messengers that improve glucose homeostasis.

Autor:	Grevengoed TJ; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark., Trammell SAJ; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark., McKinney MK; Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037.; Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037., Petersen N; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark., Cardone RL; Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06519., Svenningsen JS; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark., Ogasawara D; Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037.; Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037., Nexøe-Larsen CC; Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, 2900 Hellerup, Denmark., Knop FK; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.; Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, 2900 Hellerup, Denmark.; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.; Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen, Gentofte, 2820 Hellerup, Denmark., Schwartz TW; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark., Kibbey RG; Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06519., Cravatt BF; Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037; cravatt@scripps.edu gillum@sund.ku.dk.; Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037., Gillum MP; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; cravatt@scripps.edu gillum@sund.ku.dk.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2019 Dec 03; Vol. 116 (49), pp. 24770-24778. Date of Electronic Publication: 2019 Nov 18.
DOI:	10.1073/pnas.1916288116
Abstrakt:	Fatty acid amide hydrolase (FAAH) degrades 2 major classes of bioactive fatty acid amides, the N -acylethanolamines (NAEs) and N -acyl taurines (NATs), in central and peripheral tissues. A functional polymorphism in the human FAAH gene is linked to obesity and mice lacking FAAH show altered metabolic states, but whether these phenotypes are caused by elevations in NAEs or NATs is unknown. To overcome the problem of concurrent elevation of NAEs and NATs caused by genetic or pharmacological disruption of FAAH in vivo, we developed an engineered mouse model harboring a single-amino acid substitution in FAAH (S268D) that selectively disrupts NAT, but not NAE, hydrolytic activity. The FAAH-S268D mice accordingly show substantial elevations in NATs without alterations in NAE content, a unique metabolic profile that correlates with heightened insulin sensitivity and GLP-1 secretion. We also show that N -oleoyl taurine (C18:1 NAT), the most abundant NAT in human plasma, decreases food intake, improves glucose tolerance, and stimulates GPR119-dependent GLP-1 and glucagon secretion in mice. Together, these data suggest that NATs act as a class of lipid messengers that improve postprandial glucose regulation and may have potential as investigational metabolites to modify metabolic disease. Competing Interests: The authors declare no competing interest.
Databáze:	MEDLINE
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