Journal ArticleDOI
Oleylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-α
Jin Fu,Silvana Gaetani,Fariba Oveisi,Jesse Lo Verme,Antonia Serrano,Fernando Rodríguez de Fonseca,Anja Rosengarth,Hartmut Luecke,Barbara Di Giacomo,Giorgio Tarzia,Daniele Piomelli +10 more
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TLDR
The results, which show that OEA induces satiety by activating PPAR-α, identify an unexpected role for this nuclear receptor in regulating behaviour, and raise possibilities for the treatment of eating disorders, are identified.Abstract:
Oleylethanolamide (OEA) is a naturally occurring lipid that regulates satiety and body weight. Although structurally related to the endogenous cannabinoid anandamide, OEA does not bind to cannabinoid receptors and its molecular targets have not been defined. Here we show that OEA binds with high affinity to the peroxisome-proliferator-activated receptor-alpha (PPAR-alpha), a nuclear receptor that regulates several aspects of lipid metabolism. Administration of OEA produces satiety and reduces body weight gain in wild-type mice, but not in mice deficient in PPAR-alpha. Two distinct PPAR-alpha agonists have similar effects that are also contingent on PPAR-alpha expression, whereas potent and selective agonists for PPAR-gamma and PPAR-beta/delta are ineffective. In the small intestine of wild-type but not PPAR-alpha-null mice, OEA regulates the expression of several PPAR-alpha target genes: it initiates the transcription of proteins involved in lipid metabolism and represses inducible nitric oxide synthase, an enzyme that may contribute to feeding stimulation. Our results, which show that OEA induces satiety by activating PPAR-alpha, identify an unexpected role for this nuclear receptor in regulating behaviour, and raise possibilities for the treatment of eating disorders.read more
Citations
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The Endocannabinoid System as an Emerging Target of Pharmacotherapy
TL;DR: A comprehensive overview on the current state of knowledge of the endocannabinoid system as a target of pharmacotherapy is provided.
Journal ArticleDOI
The molecular logic of endocannabinoid signalling
TL;DR: The endocannabinoids are a family of lipid messengers that engage the cell surface receptors that are targeted by Δ9-tetrahydrocannabinol, the active principle in marijuana (Cannabis).
Journal ArticleDOI
International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid Receptors and Their Ligands: Beyond CB1 and CB2
Roger G. Pertwee,Allyn C. Howlett,Mary E. Abood,Stephen P.H. Alexander,V. Di Marzo,Maurice R. Elphick,Peter J. Greasley,Harald S. Hansen,George Kunos,Ken Mackie,Raphael Mechoulam,Ruth Alexandra Ross +11 more
TL;DR: This review summarizes current data indicating the extent to which cannabinoid receptor ligands undergo orthosteric or allosteric interactions with non- CB1, non-CB2 established GPCRs, deorphanized receptors such as GPR55, ligand-gated ion channels, transient receptor potential (TRP) channels, and other ion channels or peroxisome proliferator-activated nuclear receptors.
Journal ArticleDOI
International Union of Pharmacology. LXI. Peroxisome Proliferator-Activated Receptors
Liliane Michalik,Johan Auwerx,Joel P. Berger,V. Krishna K. Chatterjee,Christopher K. Glass,Frank J. Gonzalez,Paul Grimaldi,Takashi Kadowaki,Mitchell A. Lazar,Stephen O'Rahilly,Colin N. A. Palmer,Jorge Plutzky,Janardan K. Reddy,Bruce M. Spiegelman,Bart Staels,Walter Wahli +15 more
TL;DR: The three peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors of the nuclear hormone receptor superfamily as discussed by the authors, which share a high degree of structural homology with all members of the superfamily, particularly in the DNA-binding domain and ligand and cofactor binding domain.
Journal ArticleDOI
The emerging role of the endocannabinoid system in endocrine regulation and energy balance.
TL;DR: The ability of the endocannabinoid system to control appetite, food intake, and energy balance has recently received great attention, particularly in the light of the different modes of action underlying these functions.
References
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Journal ArticleDOI
Isolation and structure of a brain constituent that binds to the cannabinoid receptor
William A. Devane,Lumir Hanus,Aviva Breuer,Roger G. Pertwee,Lesley A. Stevenson,Graeme Griffin,Dan Gibson,Asher Mandelbaum,A. Etinger,Raphael Mechoulam +9 more
TL;DR: In this article, an arachidonylethanthanolamide (anandamide) was identified in a screen for endogenous ligands for the cannabinoid receptor and its structure was determined by mass spectrometry and nuclear magnetic resonance spectroscopy and confirmed by synthesis.
Journal ArticleDOI
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Journal ArticleDOI
The Mechanisms of Action of PPARs
Joel P. Berger,David E. Moller +1 more
TL;DR: The current state of knowledge regarding the molecular mechanisms of PPAR action and the involvement of the PPARs in the etiology and treatment of several chronic diseases is presented.
Journal ArticleDOI
Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors α and δ
TL;DR: It is shown here that specific FAs, eicosanoids, and hypolipidemic drugs are ligands for PPARα or PPARδ, and a novel conformation-based assay is developed that screens activators for their ability to bind to PPAR α/δ and induce DNA binding.
Journal ArticleDOI
Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors α and γ
Steven A. Kliewer,Scott S. Sundseth,Stacey A. Jones,Peter Brown,G. Bruce Wisely,Cecilia S. Koble,Pallavi R. Devchand,Walter Wahli,Timothy M. Willson,James M. Lenhard,Jürgen M. Lehmann +10 more
TL;DR: Evidence that PPARs serve as physiological sensors of lipid levels is provided and a molecular mechanism whereby dietary fatty acids can modulate lipid homeostasis is suggested.