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Region Hovedstaden - en del af Københavns Universitetshospital
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N-acyl taurines are endogenous lipid messengers that improve glucose homeostasis

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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  • 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
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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.

OriginalsprogEngelsk
TidsskriftProceedings of the National Academy of Sciences of the United States of America
Vol/bind116
Udgave nummer49
Sider (fra-til) 24770-24778
Antal sider9
ISSN0027-8424
DOI
StatusUdgivet - 3 dec. 2019

ID: 58436211