G protein coupled receptor 18: A potential role for endocannabinoid signaling in metabolic dysfunction.
Endocannabinoids are products of dietary fatty acids that are modulated by an alteration in food intake levels. Overweight and obese individuals have substantially higher circulating levels of the arachidonic acid derived endocannabinoids, anandamide and 2-arachidonoyl glycerol, and show an altered pattern of cannabinoid receptor expression. These cannabinoid receptors are part of a large family of G protein coupled receptors (GPCRs). GPCRs are major therapeutic targets for various diseases within the cardiovascular, neurological, gastrointestinal, and endocrine systems, as well as metabolic disorders such as obesity and type 2 diabetes mellitus. Obesity is considered a state of chronic low-grade inflammation elicited by an immunological response. Interestingly, the newly deorphanized GPCR (GPR18), which is considered to be a putative cannabinoid receptor, is proposed to have an immunological function. In this review, the current scientific knowledge on GPR18 is explored including its localization, signaling pathways, and pharmacology. Importantly, the involvement of nutritional factors and potential dietary regulation of GPR18 and its (patho)physiological roles are described. Further research on this receptor and its regulation will enable a better understanding of the complex mechanisms of GPR18 and its potential as a novel therapeutic target for treating metabolic disorders.
Centre for Chronic Disease Prevention and Management, College of Health & Biomedicine, Victoria University, Melbourne, VIC, Australia.
Gayathri
G
Rajaraman
Centre for Chronic Disease Prevention and Management, College of Health & Biomedicine, Victoria University, Melbourne, VIC, Australia.
Anna
A
Simcocks
Department of Physiology, The University of Melbourne, Parkville, VIC, Australia.
Deanne H
DH
Hryciw
Department of Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia.
Dana S
DS
Hutchinson
Centre for Chronic Disease Prevention and Management, College of Health & Biomedicine, Victoria University, Melbourne, VIC, Australia.
Andrew J
AJ
McAinch
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000628:therapy; D004041:Dietary Fats / Q000008:administration & dosage; D004195:Disease Models, Animal; D063388:Endocannabinoids / Q000378:metabolism*; D002149:Energy Intake; D015316:Genetic Therapy; D005989:Glycerides / Q000378:metabolism; D006801:Humans; D009765:Obesity / Q000235:genetics / Q000628:therapy; D053284:Polyunsaturated Alkamides / Q000378:metabolism; D043882:Receptors, Cannabinoid / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction
D001095:Arachidonic Acids; D004041:Dietary Fats; D063388:Endocannabinoids; C107515:GPR18 protein, human; D005989:Glycerides; D053284:Polyunsaturated Alkamides; D043882:Receptors, Cannabinoid; D043562:Receptors, G-Protein-Coupled; C094503:glyceryl 2-arachidonate; C078814:anandamide
Diabetes; Endocannabinoids; G protein coupled receptor; GPR18; Obesity