Abstract
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.
Highlights
The low-density lipoprotein receptor-related protein 1 (LRP1 or CD91) is a type I transmembrane protein belonging to the low-density lipoprotein receptor (LDL-R) family [1]
Metabolic syndrome (MetS) is a highly prevalent disorder characterized by a combination of metabolic alterations, including dyslipidemia, impaired glucose homeostasis, and an exacerbated inflammatory process, which lead to an increased risk of type 2 Diabetes Mellitus (T2DM) and cardiovascular disease (CVD) [14]
Non-modified circulating lipoproteins bind to the specific LDL-R family members (Very low-density lipoprotein receptor (VLDL-R), apolipoprotein E (apoE) receptor 2, LDL-R, and LRP1) localized in the plasma membrane of several types of cells, which are internalized by endocytosis through a direct interaction with these receptors [27]
Summary
The low-density lipoprotein receptor-related protein 1 (LRP1 or CD91) is a type I transmembrane protein belonging to the low-density lipoprotein receptor (LDL-R) family [1]. Based on its ability to exert complex and multi-molecular extraand intracellular functions, LRP1 has been shown to be involved in MetS. In this way, this receptor plays a key role in the uptake and processing of modified and non-modified lipoproteins in different tissues, which is associated with the promotion of intracellular lipid accumulation occurring during dyslipidemia [15,16,17]. We report on the current understanding of the potential role of tissue-specific LRP1 in lipid and glucose metabolism control along with examining its ability to mediate inflammatory processes with respect to the development of MetS
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