Its obligate requirement for the stable expression of oligomeric receptor. Asialoglycoprotein receptor deficiency in mice lacking the major receptor subunit. Deficiency of ASGR1 in pigs recapitulates reduced risk factor for cardiovascular disease in humans. Hypomorphic ASGR1 modulates lipid homeostasis via INSIG1-mediated SREBP signaling suppression. Liver X receptors in lipid signalling and membrane homeostasis. Regulation of ATP-binding cassette sterol transporters ABCG5 and ABCG8 by the liver X receptors α and β. Overexpression of ABCG5 and ABCG8 promotes biliary cholesterol secretion and reduces fractional absorption of dietary cholesterol. Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters. The residual risk reduction initiative: a call to action to reduce residual vascular risk in dyslipidaemic patients. The cholesterol absorption inhibitor ezetimibe acts by blocking the sterol-induced internalization of NPC1L1. Mechanisms and regulation of cholesterol homeostasis. Carbohydrate-specific receptors of the liver. Variant ASGR1 associated with a reduced risk of coronary artery disease. China cardiovascular diseases report 2018: an updated summary. In summary, this study demonstrates that targeting ASGR1 upregulates LXRα, ABCA1 and ABCG5/G8, inhibits SREBP1 and lipogenesis, and therefore promotes cholesterol excretion and decreases lipid levels. Anti-ASGR1 neutralizing antibody lowers lipid levels by increasing cholesterol excretion, and shows synergistic beneficial effects with atorvastatin or ezetimibe, two widely used hypocholesterolaemic drugs. On the other hand, AMPK suppresses SREBP1 that controls lipogenesis. On one hand, AMPK increases LXRα by decreasing its ubiquitin ligases BRCA1/BARD1. ASGR1 deficiency blocks endocytosis and lysosomal degradation of glycoproteins, reduces amino-acid levels in lysosomes, and thereby inhibits mTORC1 and activates AMPK. LXRα upregulates ABCA1 and ABCG5/G8, which promotes cholesterol transport to high-density lipoprotein and excretion to bile and faeces 4, respectively. Here, we find that Asgr1 deficiency decreases lipid levels in serum and liver by stabilizing LXRα. The mechanism by which ASGR1 affects cholesterol metabolism is unknown. ASGR1 is exclusively expressed in liver and mediates internalization and lysosomal degradation of blood asialoglycoproteins 3. Human genetic studies have identified that the loss-of-function Asialoglycoprotein receptor 1 ( ASGR1) variants associate with low cholesterol and a reduced risk of cardiovascular disease 2. Currently, no drug lowers cholesterol through directly promoting cholesterol excretion. High cholesterol is a major risk factor for cardiovascular disease 1.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |