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

Sci Rep. 2021 Apr 13;11(1):8003. doi: 10.1038/s41598-021-87568-2.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoproteins E / deficiency
  • Aspartate-Ammonia Ligase / genetics
  • Aspartate-Ammonia Ligase / metabolism
  • Diet, Protein-Restricted
  • Fatty Liver / blood
  • Fatty Liver / complications*
  • Fatty Liver / metabolism*
  • Fibroblast Growth Factors / deficiency
  • Gene Expression Regulation
  • Inflammation / blood
  • Inflammation / complications
  • Lipids / blood
  • Liver / injuries
  • Liver / metabolism*
  • Liver / pathology
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Organ Specificity
  • Protein Deficiency / blood
  • Protein Deficiency / complications*
  • Protein Deficiency / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, LDL / genetics
  • Receptors, LDL / metabolism*


  • Apolipoproteins E
  • Lipids
  • RNA, Messenger
  • Receptors, LDL
  • VLDL receptor
  • fibroblast growth factor 21
  • Fibroblast Growth Factors
  • Aspartate-Ammonia Ligase