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

Abstract

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.

• Authors: Trisha J Grevengoed, Samuel A J Trammell, Michele K McKinney, Natalia Petersen, Rebecca L Cardone, Jens S Svenningsen, Daisuke Ogasawara, Christina C Nexøe-Larsen, Filip K Knop, Thue W Schwartz, Richard G Kibbey, Benjamin F Cravatt, Matthew P Gillum
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 116 Issue 49 Pg. 24770-24778 (12 03 2019) ISSN: 1091-6490 [Electronic] United States
• PMID: 31740614 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Ethanolamines
• GPR119 protein, human
• Gpr119 protein, mouse
• Insulin
• N-acylethanolamines
• N-oleoyl taurine
• Oleic Acids
• Receptors, G-Protein-Coupled
• Taurine
• Glucagon-Like Peptide 1
• Glucagon
• Amidohydrolases
• fatty-acid amide hydrolase

Topics

• Amidohydrolases (genetics, metabolism)
• Amino Acid Substitution
• Animals
• Blood Glucose (analysis, metabolism)
• Disease Models, Animal
• Eating (drug effects, physiology)
• Ethanolamines (blood, metabolism)
• Female
• Glucagon (metabolism)
• Glucagon-Like Peptide 1 (metabolism)
• Glucose Tolerance Test
• Humans
• Injections, Intravenous
• Insulin (metabolism)
• Islets of Langerhans (drug effects, metabolism)
• Male
• Metabolic Syndrome (blood, drug therapy, genetics, metabolism)
• Mice
• Mice, Transgenic
• Middle Aged
• Oleic Acids (administration & dosage, blood, metabolism)
• Postprandial Period (drug effects, physiology)
• Receptors, G-Protein-Coupled (metabolism)
• Taurine (administration & dosage, analogs & derivatives, blood, metabolism)