Very low-density lipoprotein receptor increases in a liver-specific manner due to protein deficiency but does not affect fatty liver in mice

Abstract

Very low-density lipoprotein receptor (VLDLR) is a member of the LDL receptor family that is involved in the uptake of VLDL into cells. Increased hepatic VLDLR under endoplasmic reticulum (ER) stress has been shown to cause fatty liver. In this study, the effect of dietary protein restriction on hepatic VLDLR and the role of VLDLR in fatty liver were investigated using Vldlr knockout (KO) mice. Growing wild-type (WT) and KO mice were fed a control diet containing 20% ​​protein or a low protein diet containing 3% protein for 11 days. In WT mice, the amount of hepatic Vldlr mRNA and VLDLR protein increased by approximately 8- and 7-fold, respectively, due to protein restriction. Vldlr mRNA and protein levels increased in both type 1 and type 2 VLDLR. However, neither Vldlr mRNA nor protein levels were significantly increased in heart, muscle, and adipose tissue, demonstrating that VLDLR increase due to protein restriction occurred in a liver-specific manner. Increased liver triglyceride levels during protein restriction occurred in KO mice to the same extent as in WT mice, indicating that increased VLDLR during protein restriction was not the main cause of fatty liver, which was different from the case of ER stress.

Microarray analysis identifies coding and non-coding RNA markers of liver injury in whole body irradiated mice

“…Both Abcd2 and Abca8 are ATP Binding Cassette family members relevant to lipid metabolism 79 , 80 . While Very low density lipoprotein receptor (Vldlr) mediates lipid uptake and accumulation 81 , 82 . These changes may give insight into energy production pathways within the liver after radiation injury and potential biomarkers to understand liver damage and response over time.…”

Short-Term Growth Hormone Administration Mediates Hepatic Fatty Acid Uptake and De Novo Lipogenesis Gene Expression in Obese Rats

“…Our findings demonstrate that the VLDLR mRNA expression was upregulated in the obese state. There is evidence that VLDLR is upregulated in response to endoplasmic reticulum (ER) stress [ 52 ]. However, this effect was interesting to further investigate the underlying mechanisms which could be attributed to fenofibrate, the lipid-lowering agent.…”

Molecular Mechanisms and Mediators of Hepatotoxicity Resulting from an Excess of Lipids and Non-Alcoholic Fatty Liver Disease

“…Members of the LDL receptor (LDLR) gene family and the multifunctional VLDL receptor (VLDLR) have structural similarities [122]. VLDLR comprises five distinct protein domains, namely, a single transmembrane domain, an O-linked glycosylation sugar domain, an extracellular N-terminal ligand-binding region with eight cysteine-rich repeats, and a cytoplasmic domain containing the NPxY motif for signal transduction [123]. The low-density lipoprotein receptor (LDLR) has five cysteine-rich repeats, whereas the human VLDLR has only one [123].…”

“…VLDLR comprises five distinct protein domains, namely, a single transmembrane domain, an O-linked glycosylation sugar domain, an extracellular N-terminal ligand-binding region with eight cysteine-rich repeats, and a cytoplasmic domain containing the NPxY motif for signal transduction [123]. The low-density lipoprotein receptor (LDLR) has five cysteine-rich repeats, whereas the human VLDLR has only one [123]. These two variants of the receptor are revealed by the isolation and characterization of the cDNAs encoding human VLDLR [123].…”

“…The low-density lipoprotein receptor (LDLR) has five cysteine-rich repeats, whereas the human VLDLR has only one [123]. These two variants of the receptor are revealed by the isolation and characterization of the cDNAs encoding human VLDLR [123]. Additionally, VLDLR alternative splicing produces a variety of transcript variants that each encode a different isoform; however, the expression of these proteins and their precise activities have not yet been determined [123].…”