Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba X5000HUA, Argentina.
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Córdoba X5000HUA, Argentina.
Int J Mol Sci. 2018 Jun 15;19(6):1780. doi: 10.3390/ijms19061780.
Metabolic syndrome (MetS) is a highly prevalent disorder which can be used to identify individuals with a higher risk for cardiovascular disease and type 2 diabetes. This metabolic syndrome is characterized by a combination of physiological, metabolic, and molecular alterations such as insulin resistance, dyslipidemia, and central obesity. The low-density lipoprotein receptor-related protein 1 (LRP1—A member of the LDL receptor family) is an endocytic and signaling receptor that is expressed in several tissues. It is involved in the clearance of chylomicron remnants from circulation, and has been demonstrated to play a key role in the lipid metabolism at the hepatic level. Recent studies have shown that LRP1 is involved in insulin receptor (IR) trafficking and intracellular signaling activity, which have an impact on the regulation of glucose homeostasis in adipocytes, muscle cells, and brain. In addition, LRP1 has the potential to inhibit or sustain inflammation in macrophages, depending on its cellular expression, as well as the presence of particular types of ligands in the extracellular microenvironment. In this review, we summarize existing perspectives and the latest innovations concerning the role of tissue-specific LRP1 in lipoprotein and glucose metabolism, and examine its ability to mediate inflammatory processes related to MetS and atherosclerosis.
代谢综合征(MetS)是一种高发疾病,可以用来识别心血管疾病和 2 型糖尿病风险较高的个体。这种代谢综合征的特征是存在多种生理、代谢和分子改变,如胰岛素抵抗、血脂异常和中心性肥胖。低密度脂蛋白受体相关蛋白 1(LRP1—LDL 受体家族的一员)是一种内吞和信号受体,在多种组织中表达。它参与清除循环中的乳糜微粒残粒,并且已被证明在肝脏水平的脂质代谢中发挥关键作用。最近的研究表明,LRP1 参与胰岛素受体(IR)的运输和细胞内信号活性,这对调节脂肪细胞、肌肉细胞和大脑中的葡萄糖稳态有影响。此外,LRP1 有可能根据其细胞表达以及细胞外微环境中特定类型配体的存在,抑制或维持巨噬细胞中的炎症。在这篇综述中,我们总结了关于组织特异性 LRP1 在脂蛋白和葡萄糖代谢中的作用的现有观点和最新进展,并研究了它介导与 MetS 和动脉粥样硬化相关的炎症过程的能力。