Deorphanization of a G protein-coupled receptor for oleoylethanolamide and its use in the discovery of small-molecule hypophagic agents

Cell Metabolism
H A OvertonC Reynet

Abstract

The endogenous lipid signaling agent oleoylethanolamide (OEA) has recently been described as a peripherally acting agent that reduces food intake and body weight gain in rat feeding models. This paper presents evidence that OEA is an endogenous ligand of the orphan receptor GPR119, a G protein-coupled receptor (GPCR) expressed predominantly in the human and rodent pancreas and gastrointestinal tract and also in rodent brain, suggesting that the reported effects of OEA on food intake may be mediated, at least in part, via the GPR119 receptor. Furthermore, we have used the recombinant receptor to discover novel selective small-molecule GPR119 agonists, typified by PSN632408, which suppress food intake in rats and reduce body weight gain and white adipose tissue deposition upon subchronic oral administration to high-fat-fed rats. GPR119 therefore represents a novel and attractive potential target for the therapy of obesity and related metabolic disorders.

References

Oct 1, 1993·Journal of Medicinal Chemistry·L HanusR Mechoulam
Sep 7, 1999·Bioorganic & Medicinal Chemistry Letters·R M CampbellA L Castelhano
Nov 26, 1999·Proceedings of the National Academy of Sciences of the United States of America·Z JáraiG Kunos
Nov 9, 2001·Nature·F Rodríguez de FonsecaD Piomelli
Dec 26, 2001·The Journal of Biological Chemistry·Juan J MiretBert Oehlen
Dec 24, 2002·The Journal of Biological Chemistry·Celia P BriscoeAlison I Muir
Mar 12, 2003·International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity·D CotaU Pagotto
Mar 21, 2003·Journal of Medicinal Chemistry·Mark C WenlockPaul D Leeson
Apr 18, 2003·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Silvana GaetaniDaniele Piomelli
Mar 5, 2004·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Fariba OveisiDaniele Piomelli
Apr 3, 2004·Journal of Lipid Research·Mie Julin NielsenHarald S Hansen
Jun 8, 2004·The Journal of Clinical Endocrinology and Metabolism·Cynthia J Stein, Graham A Colditz
Oct 12, 2004·Drug Discovery Today·Ronald J Jandacek, Stephen C Woods
Dec 21, 2004·Biochemical and Biophysical Research Communications·Takatoshi SogaKiyoshi Furuichi
Dec 28, 2004·Nature Medicine·Akira HirasawaGozoh Tsujimoto
May 10, 2005·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Karine ProulxRandy J Seeley

❮ Previous
Next ❯

Citations

Apr 25, 2012·Histochemistry and Cell Biology·H BreerP Widmayer
Dec 31, 2011·Human Genetics·Eric W KleeStephen C Ekker
Dec 25, 2010·Pharmaceutical Research·Renger F Witkamp
Oct 23, 2009·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Luciano De Petrocellis, Vincenzo Di Marzo
Aug 16, 2008·Lipids·Clémentine ThabuisFrédéric Destaillats
Oct 24, 2007·Molecular Neurobiology·Christopher J Fowler
Apr 10, 2013·Trends in Endocrinology and Metabolism : TEM·Daniele Piomelli
Aug 22, 2012·The Proceedings of the Nutrition Society·Fiona M Gribble
Jan 6, 2010·Expert Reviews in Molecular Medicine·Helen E ParkerFiona M Gribble
Aug 4, 2012·ACS Chemical Neuroscience·Tatsuya TaiNatsuo Ueda
Dec 6, 2012·Journal of Medicinal Chemistry·Bernd WellenzohnBernd Nosse
Dec 14, 2012·Journal of Medicinal Chemistry·Etzer DaroutYue Chen
Jul 20, 2013·Journal of Medicinal Chemistry·Sangdon HanRobert M Jones
Mar 1, 2012·Acta Pharmacologica Sinica·Xiao-long TangMing-yao Liu
Apr 3, 2008·Nature Reviews. Drug Discovery·Malin C Lagerström, Helgi B Schiöth
Oct 2, 2007·British Journal of Pharmacology·Y SunA J Bennett
Sep 30, 2010·Proceedings of the National Academy of Sciences of the United States of America·Reem SmoumRaphael Mechoulam
Aug 23, 2012·Proceedings of the National Academy of Sciences of the United States of America·Whitney H BrownGerald I Shulman
Nov 24, 2006·The Journal of Biological Chemistry·Jin FuDaniele Piomelli
Dec 20, 2007·Current Opinion in Nephrology and Hypertension·Jun Wang, Natsuo Ueda
Oct 13, 2009·Diabetes, Obesity & Metabolism·M A KebedeV Poitout
Jul 22, 2010·Annual Review of Nutrition·Mauro MaccarroneLuciana Avigliano
Apr 25, 2008·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Jin FuDaniele Piomelli
Jul 20, 2012·Physiological Reviews·Nada A Abumrad, Nicholas O Davidson
Jul 20, 2012·International Journal of Endocrinology·Amedeo Vetere, Bridget K Wagner
Aug 1, 2010·Therapeutic Advances in Endocrinology and Metabolism·Venkat VangavetiR Lee Kennedy
Sep 26, 2007·BMC Genomics·David E GloriamHelgi B Schiöth
May 7, 2010·The AAPS Journal·Akihiko OzawaWesley K Kroeze
May 18, 2007·Endocrinology·S R Murthy Madiraju, Vincent Poitout
Nov 17, 2010·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Shigeru Yoshida
Jul 13, 2011·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Kazuhito Tsuboi, Natsuo Ueda

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.