GPR146 Deficiency Protects against Hypercholesterolemia and Atherosclerosis - Archive ouverte HAL
Article Dans Une Revue Cell Année : 2019

GPR146 Deficiency Protects against Hypercholesterolemia and Atherosclerosis

Yulei Xia
  • Fonction : Auteur
Fang Xia
  • Fonction : Auteur
Tao Chen
  • Fonction : Auteur

Résumé

Although human genetic studies have implicated many susceptible genes associated with plasma lipid levels, their physiological and molecular functions are not fully characterized. Here we demonstrate that orphan G protein-coupled receptor 146 (GPR146) promotes activity of hepatic sterol regulatory element binding protein 2 (SREBP2) through activation of the extracellular signal-regulated kinase (ERK) signaling pathway, thereby regulating hepatic very low-density lipoprotein (VLDL) secretion, and subsequently circulating low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) levels. Remarkably, GPR146 deficiency reduces plasma cholesterol levels substantially in both wild-type and LDL receptor (LDLR)-deficient mice. Finally, aortic atherosclerotic lesions are reduced by 90% and 70%, respectively, in male and female LDLR-deficient mice upon GPR146 depletion. Taken together, these findings outline a regulatory role for the GPR146/ERK axis in systemic cholesterol metabolism and suggest that GPR146 inhibition could be an effective strategy to reduce plasma cholesterol levels and atherosclerosis.
Fichier principal
Vignette du fichier
main.pdf (2.87 Mo) Télécharger le fichier
Origine Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-02422749 , version 1 (23-09-2024)

Identifiants

Citer

Haojie Yu, Antoine Rimbert, Alice Palmer, Takafumi Toyohara, Yulei Xia, et al.. GPR146 Deficiency Protects against Hypercholesterolemia and Atherosclerosis. Cell, 2019, 179 (6), pp.1276-1288.e14. ⟨10.1016/j.cell.2019.10.034⟩. ⟨hal-02422749⟩
97 Consultations
6 Téléchargements

Altmetric

Partager

More