title: Deficiency in apolipoprotein E has a protective effect on diet-induced nonalcoholic fatty liver disease in mice.
abstract: 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.
authors: Department of Medicine, Pharmacology Unit, University of Patras School of Health Sciences, Rio-Achaias, Greece.
authors: Eleni A
authors: EA
authors: Karavia
authors: Dionysios J
authors: DJ
authors: Papachristou
authors: Ioanna
authors: I
authors: Kotsikogianni
authors: Ioanna
authors: I
authors: Giopanou
authors: Kyriakos E
authors: KE
authors: Kypreos
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004041:Dietary Fats / Q000009:adverse effects*; D005234:Fatty Liver / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D055879:Gene Knock-In Techniques; D006801:Humans; D007700:Kinetics; D008079:Lipoproteins, VLDL / Q000097:blood / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D019518:Postprandial Period; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D014280:Triglycerides / Q000097:blood / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D004041:Dietary Fats; D008079:Lipoproteins, VLDL; D011973:Receptors, LDL; D014280:Triglycerides