Fatty acid mimetic PBI-4547 restores metabolic homeostasis via GPR84 in mice with non-alcoholic fatty liver disease.

Acetates / pharmacology Animals Binding, Competitive Biosensing Techniques Cholesterol / metabolism Disease Models, Animal Disease Progression Drug Discovery Fatty Acids / pharmacology Female Glucose / metabolism Glucose Tolerance Test HEK293 Cells Homeostasis Humans Ligands Magnetic Resonance Spectroscopy Male Metabolomics Mice Mitochondria / metabolism Non-alcoholic Fatty Liver Disease / drug therapy Obesity / metabolism Oxygen / metabolism Plasmids / metabolism Protein Binding Receptors, G-Protein-Coupled / metabolism

Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
29 07 2020
Historique:
received: 17 09 2019
accepted: 14 07 2020
entrez: 31 7 2020
pubmed: 31 7 2020
medline: 14 1 2021
Statut: epublish

Résumé

Non-alcoholic Fatty Liver Disease (NAFLD) is the most common form of liver disease and is associated with metabolic dysregulation. Although G protein-coupled receptor 84 (GPR84) has been associated with inflammation, its role in metabolic regulation remains elusive. The aim of our study was to evaluate the potential of PBI-4547 for the treatment of NAFLD and to validate the role of its main target receptor, GPR84. We report that PBI-4547 is a fatty acid mimetic, acting concomitantly as a GPR84 antagonist and GPR40/GPR120 agonist. In a mouse model of diet-induced obesity, PBI-4547 treatment improved metabolic dysregulation, reduced hepatic steatosis, ballooning and NAFLD score. PBI-4547 stimulated fatty acid oxidation and induced gene expression of mitochondrial uncoupling proteins in the liver. Liver metabolomics revealed that PBI-4547 improved metabolic dysregulation induced by a high-fat diet regimen. In Gpr84

Identifiants

DOI: 10.1038/s41598-020-69675-8 PMID: 32728158 PMC: PMC7391726
pubmed: 32728158
doi: 10.1038/s41598-020-69675-8
pii: 10.1038/s41598-020-69675-8
pmc: PMC7391726
doi:

Substances chimiques

Acetates 0
Fatty Acids 0
Gpr84 protein, mouse 0
Ligands 0
PBI-4547 0
Receptors, G-Protein-Coupled 0
Cholesterol 97C5T2UQ7J
Glucose IY9XDZ35W2
Oxygen S88TT14065

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

12778

Références

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Auteurs

Jean-Christophe Simard (JC)

Liminal R&D Biosciences Inc., 500 Boulevard Cartier Ouest (Suite 150), Laval, QC, H7V 5B7, Canada.

Jean-François Thibodeau (JF)

Liminal R&D Biosciences Inc., 500 Boulevard Cartier Ouest (Suite 150), Laval, QC, H7V 5B7, Canada. j.thibodeau@liminalbiosciences.com.
Department of Cellular and Molecular Medicine, Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada. j.thibodeau@liminalbiosciences.com.

Martin Leduc (M)

Liminal R&D Biosciences Inc., 500 Boulevard Cartier Ouest (Suite 150), Laval, QC, H7V 5B7, Canada.

Mikael Tremblay (M)

Liminal R&D Biosciences Inc., 500 Boulevard Cartier Ouest (Suite 150), Laval, QC, H7V 5B7, Canada.

Alexandre Laverdure (A)

Liminal R&D Biosciences Inc., 500 Boulevard Cartier Ouest (Suite 150), Laval, QC, H7V 5B7, Canada.

François Sarra-Bournet (F)

Liminal R&D Biosciences Inc., 500 Boulevard Cartier Ouest (Suite 150), Laval, QC, H7V 5B7, Canada.

William Gagnon (W)

Liminal R&D Biosciences Inc., 500 Boulevard Cartier Ouest (Suite 150), Laval, QC, H7V 5B7, Canada.

Jugurtha Ouboudinar (J)

Liminal R&D Biosciences Inc., 500 Boulevard Cartier Ouest (Suite 150), Laval, QC, H7V 5B7, Canada.

Liette Gervais (L)

Liminal R&D Biosciences Inc., 500 Boulevard Cartier Ouest (Suite 150), Laval, QC, H7V 5B7, Canada.

Alexandra Felton (A)

Liminal R&D Biosciences Inc., 500 Boulevard Cartier Ouest (Suite 150), Laval, QC, H7V 5B7, Canada.

Sylvie Letourneau (S)

Liminal R&D Biosciences Inc., 500 Boulevard Cartier Ouest (Suite 150), Laval, QC, H7V 5B7, Canada.

Lilianne Geerts (L)

Liminal R&D Biosciences Inc., 500 Boulevard Cartier Ouest (Suite 150), Laval, QC, H7V 5B7, Canada.

Marie-Pier Cloutier (MP)

Liminal R&D Biosciences Inc., 500 Boulevard Cartier Ouest (Suite 150), Laval, QC, H7V 5B7, Canada.

Kathy Hince (K)

Liminal R&D Biosciences Inc., 500 Boulevard Cartier Ouest (Suite 150), Laval, QC, H7V 5B7, Canada.

Ramon Corpuz (R)

Liminal R&D Biosciences Inc., 500 Boulevard Cartier Ouest (Suite 150), Laval, QC, H7V 5B7, Canada.

Alexandra Blais (A)

Liminal R&D Biosciences Inc., 500 Boulevard Cartier Ouest (Suite 150), Laval, QC, H7V 5B7, Canada.

Vanessa Marques Quintela (VM)

Liminal R&D Biosciences Inc., 500 Boulevard Cartier Ouest (Suite 150), Laval, QC, H7V 5B7, Canada.

Jean-Simon Duceppe (JS)

Liminal R&D Biosciences Inc., 500 Boulevard Cartier Ouest (Suite 150), Laval, QC, H7V 5B7, Canada.

Shaun D Abbott (SD)

Liminal R&D Biosciences Inc., 500 Boulevard Cartier Ouest (Suite 150), Laval, QC, H7V 5B7, Canada.

Amélie Blais (A)

Department of Cellular and Molecular Medicine, Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada.

Boulos Zacharie (B)

Liminal R&D Biosciences Inc., 500 Boulevard Cartier Ouest (Suite 150), Laval, QC, H7V 5B7, Canada.

Pierre Laurin (P)

Liminal R&D Biosciences Inc., 500 Boulevard Cartier Ouest (Suite 150), Laval, QC, H7V 5B7, Canada.

Steven R Laplante (SR)

Institut National de La Recherche Scientifique, Institut Armand-Frappier, 531 Boul. Des Prairies, Laval, QC, H7V 5B7, Canada.

Christopher R J Kennedy (CRJ)

Department of Cellular and Molecular Medicine, Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada.

Richard L Hébert (RL)

Department of Cellular and Molecular Medicine, Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada.

François A Leblond (FA)

Liminal R&D Biosciences Inc., 500 Boulevard Cartier Ouest (Suite 150), Laval, QC, H7V 5B7, Canada.

Brigitte Grouix (B)

Liminal R&D Biosciences Inc., 500 Boulevard Cartier Ouest (Suite 150), Laval, QC, H7V 5B7, Canada.

Lyne Gagnon (L)

Liminal R&D Biosciences Inc., 500 Boulevard Cartier Ouest (Suite 150), Laval, QC, H7V 5B7, Canada.

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Classifications MeSH

questionsmedicales.fr › Lipides › Acides gras › Acides gras volatils › Acétates › Fatty acid mimetic PBI-4547 restores metabolic...
questionsmedicales.fr › Eucaryotes › Animaux › Fatty acid mimetic PBI-4547 restores metabolic...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Sites de fixation › Fixation compétitive › Fatty acid mimetic PBI-4547 restores metabolic...
questionsmedicales.fr › Techniques d'investigation › Techniques de sonde moléculaire › Techniques de biocapteur › Fatty acid mimetic PBI-4547 restores metabolic...
questionsmedicales.fr › Lipides › Lipides membranaires › Stérols › Cholestérol › Fatty acid mimetic PBI-4547 restores metabolic...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › Fatty acid mimetic PBI-4547 restores metabolic...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Évolution de la maladie › Fatty acid mimetic PBI-4547 restores metabolic...
questionsmedicales.fr › Techniques d'investigation › Développement de médicament › Découverte de médicament › Fatty acid mimetic PBI-4547 restores metabolic...
questionsmedicales.fr › Lipides › Acides gras › Fatty acid mimetic PBI-4547 restores metabolic...
questionsmedicales.fr › Glucides › Sucres › Oses › Hexose › Glucose › Fatty acid mimetic PBI-4547 restores metabolic...
questionsmedicales.fr › Techniques d'investigation › Techniques de laboratoire clinique › Tests de chimie clinique › Analyse chimique du sang › Hyperglycémie provoquée › Fatty acid mimetic PBI-4547 restores metabolic...
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules HEK293 › Fatty acid mimetic PBI-4547 restores metabolic...
questionsmedicales.fr › Phénomènes physiologiques › Homéostasie › Fatty acid mimetic PBI-4547 restores metabolic...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Fatty acid mimetic PBI-4547 restores metabolic...
questionsmedicales.fr › Actions chimiques et utilisations › Utilisations spécialisées de produits chimiques › Produits chimiques de laboratoire › Ligands › Fatty acid mimetic PBI-4547 restores metabolic...
questionsmedicales.fr › Techniques d'investigation › Techniques de chimie analytique › Analyse spectrale › Spectroscopie par résonance magnétique › Fatty acid mimetic PBI-4547 restores metabolic...
questionsmedicales.fr › Disciplines des sciences naturelles › Chimie › Biochimie › Métabolomique › Fatty acid mimetic PBI-4547 restores metabolic...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Fatty acid mimetic PBI-4547 restores metabolic...
questionsmedicales.fr › Cellules › Structures cellulaires › Fractions subcellulaires › Mitochondries › Fatty acid mimetic PBI-4547 restores metabolic...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies du foie › Stéatose hépatique › Stéatose hépatique non alcoolique › Fatty acid mimetic PBI-4547 restores metabolic...
questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Obésité › Fatty acid mimetic PBI-4547 restores metabolic...
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