학술논문
G protein-coupled receptor 146: new insights from genetics and model systems.
Document Type
Academic Journal
Author
Tharehalli U; Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.; Rimbert A; Nantes Université, CNRS, INSERM, l'institut du thorax, Nantes, France.
Source
Publisher: Lippincott Williams & Wilkins Country of Publication: England NLM ID: 9010000 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1473-6535 (Electronic) Linking ISSN: 09579672 NLM ISO Abbreviation: Curr Opin Lipidol Subsets: MEDLINE
Subject
Language
English
Abstract
Purpose of Review: Atherosclerotic cardiovascular diseases continue to be a significant global cause of death. Despite the availability of efficient treatments, there is an ongoing need for innovative strategies to lower lipid levels, especially for individuals experiencing refractory dyslipidemias or intolerable adverse effects. Based on human genetic findings and on mouse studies, the G protein-coupled receptor 146 (GPR146) emerges as a promising target against hypercholesterolemia and atherosclerosis. The present review aims at providing a thorough summary of the latest information acquired regarding GPR146, encompassing genetic evidence, functional insights, and its broader implications for cardiometabolic health.
Recent Findings: Human genetic studies uncovered associations between GPR146 variants, plasma lipid levels and metabolic parameters. Additionally, GPR146's influence extends beyond lipid regulation, impacting adipocyte differentiation, lipolysis, and inflammation pathways. Despite GPR146's orphan status, ongoing efforts to deorphanize it, suggest a potential ligand with downstream effects involving Gαi coupling.
Summary: Here, we outline and deliberate on recent progress focused on: enhancing comprehension of the effects of inhibiting GPR146 in humans through genetic instruments, evaluating the extra-hepatic functions of GPR146, and discovering its natural ligand(s). Grasping these biological parameters and mechanisms is crucial in the exploration of GPR146 as a prospective therapeutic target.
(Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
Recent Findings: Human genetic studies uncovered associations between GPR146 variants, plasma lipid levels and metabolic parameters. Additionally, GPR146's influence extends beyond lipid regulation, impacting adipocyte differentiation, lipolysis, and inflammation pathways. Despite GPR146's orphan status, ongoing efforts to deorphanize it, suggest a potential ligand with downstream effects involving Gαi coupling.
Summary: Here, we outline and deliberate on recent progress focused on: enhancing comprehension of the effects of inhibiting GPR146 in humans through genetic instruments, evaluating the extra-hepatic functions of GPR146, and discovering its natural ligand(s). Grasping these biological parameters and mechanisms is crucial in the exploration of GPR146 as a prospective therapeutic target.
(Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)