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

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.

Karavia EA ，Papachristou DJ ，Kotsikogianni I ，Giopanou I ，Kypreos KE ... -  《-》

Obesity potentiates development of fatty liver and insulin resistance, but not atherosclerosis, in high-fat diet-fed agouti LDLR-deficient mice.

Coenen KR ，Hasty AH 《AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM》

Effect of macrophage-derived apolipoprotein E on hyperlipidemia and atherosclerosis of LDLR-deficient mice.

Shi W ，Wang X ，Wong J ，Hedrick CC ，Wong H ，Castellani LW ，Lusis AJ ... -  《BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS》

In the absence of the low density lipoprotein receptor, human apolipoprotein C1 overexpression in transgenic mice inhibits the hepatic uptake of very low density lipoproteins via a receptor-associated protein-sensitive pathway.

Jong MC ，Dahlmans VE ，van Gorp PJ ，van Dijk KW ，Breuer ML ，Hofker MH ，Havekes LM ... -  《JOURNAL OF CLINICAL INVESTIGATION》

Urotensin II receptor knockout mice on an ApoE knockout background fed a high-fat diet exhibit an enhanced hyperlipidemic and atherosclerotic phenotype.

Bousette N ，D'Orleans-Juste P ，Kiss RS ，You Z ，Genest J ，Al-Ramli W ，Qureshi ST ，Gramolini A ，Behm D ，Ohlstein EH ，Harrison SM ，Douglas SA ，Giaid A ... -  《-》