Deficiency in apolipoprotein E has a protective effect on diet-induced nonalcoholic fatty liver disease in mice

FEBS J. 2011 Sep;278(17):3119-29. doi: 10.1111/j.1742-4658.2011.08238.x. Epub 2011 Aug 2.


Apolipoprotein E (apoE) mediates the efficient catabolism of the chylomicron remnants very low-density lipoprotein and low-density lipoprotein from the circulation, and the de novo biogenesis of high-density lipoprotein. Lipid-bound apoE is the natural ligand for the low-density lipoprotein receptor (LDLr), LDLr-related protein 1 and other scavenger receptors. Recently, we have established that deficiency in apoE renders mice resistant to diet-induced obesity. In the light of these well-documented properties of apoE, we sought to investigate its role in the development of diet-induced nonalcoholic fatty liver disease (NAFLD). apoE-deficient, LDLr-deficient and control C57BL/6 mice were fed a western-type diet (17.3% protein, 48.5% carbohydrate, 21.2% fat, 0.2% cholesterol, 4.5 kcal·g(-)) for 24 weeks and their sensitivity to NAFLD was assessed by histological and biochemical methods. apoE-deficient mice were less sensitive than control C57BL/6 mice to diet-induced NAFLD. In an attempt to identify the molecular basis for this phenomenon, biochemical and kinetic analyses revealed that apoE-deficient mice displayed a significantly delayed post-prandial triglyceride clearance from their plasma. In contrast with apoE-deficient mice, LDLr-deficient mice fed a western-type diet for 24 weeks developed significant accumulation of hepatic triglycerides and NAFLD, suggesting that apoE-mediated hepatic triglyceride accumulation in mice is independent of LDLr. Our findings suggest a new role of apoE as a key peripheral contributor to hepatic lipid homeostasis and the development of diet-induced NAFLD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoproteins E / deficiency
  • Apolipoproteins E / genetics
  • Apolipoproteins E / physiology*
  • Dietary Fats / adverse effects*
  • Fatty Liver / blood
  • Fatty Liver / pathology
  • Fatty Liver / prevention & control*
  • Gene Knock-In Techniques
  • Humans
  • Kinetics
  • Lipoproteins, VLDL / blood
  • Lipoproteins, VLDL / metabolism
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Postprandial Period
  • Receptors, LDL / deficiency
  • Receptors, LDL / genetics
  • Receptors, LDL / physiology
  • Triglycerides / blood
  • Triglycerides / metabolism


  • Apolipoproteins E
  • Dietary Fats
  • Lipoproteins, VLDL
  • Receptors, LDL
  • Triglycerides