title: Lecithin/cholesterol acyltransferase modulates diet-induced hepatic deposition of triglycerides in mice.
abstract: Lecithin/cholesterol acyltransferase (LCAT) is responsible for the esterification of the free cholesterol of plasma lipoproteins. Here, we investigated the involvement of LCAT in mechanisms associated with diet-induced hepatic triglyceride accumulation in mice. LCAT-deficient (LCAT(-/-)) and control C57BL/6 mice were placed on a Western-type diet (17.3% protein, 48.5% carbohydrate, 21.2% fat, 0.2% cholesterol, 4.5kcal/g) for 24weeks, then histopathological and biochemical analyses were performed. We report that, in our experimental setup, male LCAT(-/-) mice are characterized by increased diet-induced hepatic triglyceride deposition and impaired hepatic histology and architecture. Mechanistic analyses indicated that LCAT deficiency was associated with enhanced intestinal absorption of dietary triglycerides (3.6±0.5mg/dl per minute for LCAT(-/-) vs. 2.0±0.7mg/dl per minute for C57BL/6 mice; P<.05), accelerated clearance of postprandial triglycerides and a reduced rate of hepatic very low density lipoprotein triglyceride secretion (9.8±1.1mg/dl per minute for LCAT(-/-) vs. 12.5±1.3mg/dl per minute for C57BL/6 mice, P<.05). No statistical difference in the average daily food consumption between mouse strains was observed. Adenovirus-mediated gene transfer of LCAT in LCAT(-/-) mice that were fed a Western-type diet for 12weeks resulted in a significant reduction in hepatic triglyceride content (121.2±5.9mg/g for control infected mice vs. 95.1±5.8mg/g for mice infected with Ad-LCAT, P<.05) and a great improvement of hepatic histology and architecture. Our data extend the current knowledge on the functions of LCAT, indicating that LCAT activity is an important modulator of processes associated with diet-induced hepatic lipid deposition.
authors: Pharmacology Unit, Department of Medicine, University of Patras Medical School, Panepistimioupolis, Rio, TK 26500, Greece.
authors: Eleni A
authors: EA
authors: Karavia
authors: Dionysios J
authors: DJ
authors: Papachristou
authors: Ioanna
authors: I
authors: Kotsikogianni
authors: Irene-Eva
authors: IE
authors: Triantafyllidou
authors: Kyriakos E
authors: KE
authors: Kypreos
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001835:Body Weight; D004032:Diet; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D007863:Lecithin Cholesterol Acyltransferase Deficiency / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008079:Lipoproteins, VLDL / Q000097:blood* / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D000069463:Olive Oil; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000235:genetics / Q000378:metabolism*; D010938:Plant Oils / Q000008:administration & dosage; D019518:Postprandial Period; D014280:Triglycerides / Q000097:blood* / Q000378:metabolism
chemical_list: D008079:Lipoproteins, VLDL; D000069463:Olive Oil; D010938:Plant Oils; D014280:Triglycerides; C030106:very low density lipoprotein triglyceride; D007862:Phosphatidylcholine-Sterol O-Acyltransferase