Molecular, Genetic, and Biochemical Nutrition Commons^™

Targeted Deletion Of Hepatocyte Abca1 Leads To Very Low Density Lipoprotein Triglyceride Overproduction And Low Density Lipoprotein Hypercatabolism, Soonkyu Chung, Jenelle M. Timmins, Myngan Duong, Chiara Degirolamo, Shunxing Rong, Janet K. Sawyer, Roshni R. Singaraja, Michael R. Hayden, Nobuyo Maeda, Lawrence L. Rudel, Gregory S. Shelness, John S. Parks

Department of Nutrition and Health Sciences: Faculty Publications

Loss of ABCA1 activity in Tangier disease (TD) is associated with abnormal apoB lipoprotein (Lp) metabolism in addition to the complete absence of high density lipoprotein (HDL). We used hepatocyte-specific ABCA1 knock-out (HSKO) mice to test the hypothesis that hepatic ABCA1 plays dual roles in regulating Lp metabolism and nascent HDL formation. HSKO mice recapitulated the TD lipid phenotype with postprandial hypertriglyceridemia, markedly decreased LDL, and near absence of HDL. Triglyceride (TG) secretion was 2-fold higher in HSKO compared with wild type mice, primarily due to secretion of larger TG-enriched VLDL secondary to reduced hepatic phosphatidylinositol 3-kinase signaling. HSKO mice …