Low-Density Lipoprotein Receptor-Related Protein 6 (LRP6) Is a Novel Nutritional Therapeutic Target for Hyperlipidemia, Non-Alcoholic Fatty Liver Disease, and Atherosclerosis.
Low-Density Lipoprotein Receptor-Related Protein 6 (LRP6) Is a Novel Nutritional Therapeutic Target for Hyperlipidemia, Non-Alcoholic Fatty Liver Disease, and Atherosclerosis.
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作者：
Go GW
低密度脂蛋白受体相关蛋白6 （Low-density lipoprotein receptor related protein 6, LRP6）是低密度脂蛋白受体家族的一员，具有独特的结构，这使得其作为Wnt/β-catenin信号的共受体和内吞作用的配体受体具有多种功能。LRP6在代谢调节中的作用，特别是在营养感应途径中，最近引起了相当大的兴趣。携带LRP6突变的患者LDL胆固醇、甘油三酯和空腹血糖水平升高，这些共同构成代谢综合征和动脉粥样硬化的危险因素。自发现这一突变以来，人们对LRP6在脂质稳态、葡萄糖代谢和动脉粥样硬化中的一般作用进行了深入研究。这些研究表明LRP6在LDL受体介导的LDL摄取中起作用。此外，当LRP6突变体破坏Wnt-LRP6信号传导时，高脂血症、非酒精性脂肪性肝病和动脉粥样硬化就会发生。LRP6通过雷帕霉素（mTOR）通路的营养感应机制靶点调节脂质稳态和体脂肪量。此外，突变体LRP6通过激活血小板衍生生长因子（PDGF）依赖性血管平滑肌细胞分化引发动脉粥样硬化。这篇综述强调了研究LRP6对代谢综合征和心血管疾病的病理生理贡献的特殊机会，这意味着LRP6是脂质代谢的潜在调节剂和营养干预的新治疗靶点。
Low-density lipoprotein receptor-related protein 6 (LRP6) is a member of the low-density lipoprotein receptor family and has a unique structure, which facilitates its multiple functions as a co-receptor for Wnt/β-catenin signaling and as a ligand receptor for endocytosis. The role LRP6 plays in metabolic regulation, specifically in the nutrient-sensing pathway, has recently garnered considerable interest. Patients carrying an LRP6 mutation exhibit elevated levels of LDL cholesterol, triglycerides, and fasting glucose, which cooperatively constitute the risk factors of metabolic syndrome and atherosclerosis. Since the discovery of this mutation, the general role of LRP6 in lipid homeostasis, glucose metabolism, and atherosclerosis has been thoroughly researched. These studies have demonstrated that LRP6 plays a role in LDL receptor-mediated LDL uptake. In addition, when the LRP6 mutant impaired Wnt-LRP6 signaling, hyperlipidemia, non-alcoholic fatty liver disease, and atherosclerosis developed. LRP6 regulates lipid homeostasis and body fat mass via the nutrient-sensing mechanistic target of the rapamycin (mTOR) pathway. Furthermore, the mutant LRP6 triggers atherosclerosis by activating platelet-derived growth factor (PDGF)-dependent vascular smooth muscle cell differentiation. This review highlights the exceptional opportunities to study the pathophysiologic contributions of LRP6 to metabolic syndrome and cardiovascular diseases, which implicate LRP6 as a latent regulator of lipid metabolism and a novel therapeutic target for nutritional intervention.
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影响因子：
29
作者：
Lamming DW;Sabatini DM
通讯作者：
Sabatini DM
影响因子：
5.3
作者：
Goliasch, Georg;Wiesbauer, Franz;Speidl, Walter S.
通讯作者：
Speidl, Walter S.
DOI：
10.1056/nejmoa1301824
发表时间：
2014-05-15
期刊：
The New England journal of medicine
影响因子：
--
作者：
Keramati AR;Fathzadeh M;Go GW;Singh R;Choi M;Faramarzi S;Mane S;Kasaei M;Sarajzadeh-Fard K;Hwa J;Kidd KK;Babaee Bigi MA;Malekzadeh R;Hosseinian A;Babaei M;Lifton RP;Mani A
通讯作者：
Mani A
影响因子：
15.9
作者：
ISHIBASHI, S;BROWN, MS;HERZ, J
通讯作者：
HERZ, J
影响因子：
56.9
作者：
Bilic, Josipa;Huang, Ya-Lin;Niehrs, Christof
通讯作者：
Niehrs, Christof