The Role of Low-Density Lipoprotein Receptor-Related Protein 1 in Lipid Metabolism, Glucose Homeostasis and Inflammation

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.

Low-Density Lipoprotein Receptor-Related Protein 1 (LRP1) Is a Negative Regulator of Oligodendrocyte Progenitor Cell Differentiation in the Adult Mouse Brain

“…This large cell surface receptor, comprising a 515 kDa extracellular α-chain and an 85 kDa β-chain, could influence OPC behavior in a number of ways, as it interacts with a large variety of ligands, as well as extracellular and intracellular proteins, to facilitate signal transduction (Auderset et al, 2016b;Bres and Faissner, 2019). In other cell types, LRP1 acts as a receptor or co-receptor to initiate intracellular signal transduction, but also facilitates ligand endocytosis, transcytosis, or processing (Cam et al, 2005;Parkyn et al, 2008;Su et al, 2008;Yamamoto et al, 2014;Liu et al, 2017;Van Gool et al, 2019;Rauch et al, 2020), as well as receptor, channel and transporter trafficking (Parkyn et al, 2008;Maier et al, 2013;Nakajima et al, 2013;Liu et al, 2015;Boyé et al, 2017;Kadurin et al, 2017;Wujak et al, 2018) to influence blood brain barrier permeability (Polavarapu et al, 2007), lipid metabolism, glucose homeostasis, neuroinflammation (Brifault et al, 2017(Brifault et al, , 2019; Actis Dato and Chiabrando, 2018) and synaptic plasticity (Zhuo et al, 2000).…”

Molecular Chaperones: Molecular Assembly Line Brings Metabolism and Immunity in Shape

“…exHSP90 (gp96) has been shown to bind to surface receptor CD91 (low-density lipoprotein receptor-related protein 1 (LRP1)) [ 31 ] for promoting wound healing [ 192 ] and tumor cell invasion [ 193 ]. It is known that CD91 is essential for not only phagocytosis, immunosurveillance and Th cell priming [ 194 , 195 , 196 ], but it is also associated with the regulation of lipid metabolism, glucose homeostasis and inflammation in metabolic syndromes [ 197 ]. Collectively, it is likely that exHSPs could act as crucial modulators of metabolism, epigenetics and inflammation in the development and differentiation of immune cells during pathogenesis.…”

Contribution of the Low-Density Lipoprotein Receptor Family to Breast Cancer Progression

“…LRP-1 is highly expressed in preadipocytes and is involved in adipocyte differentiation, especially through its regulation of peroxisome proliferator-activated receptor γ ( 67 ). LRP1 has also been demonstrated to be upregulated in obese mouse adipocytes and obese human adipose tissues ( 67 ) and to regulate insulin receptor and GLUT4 trafficking and activation ( 68 , 69 ). Through modulation of Wnt5a signaling, LRP1 controls cholesterol storage and fatty acid synthesis during adipocyte differentiation ( 70 ).…”