Dietary cholic acid lowers plasma levels of mouse and human apolipoprotein A‐I primarily via a transcriptional mechanism

摘要: To induce dietary atherosclerosis in mice, high-fat/high-cholesterol (HF) diets are frequently supplemented with cholic acid (CA). This diet produces low plasma levels of high-density lipoprotein (HDL) and high low-density (LDL). However, HF without any added CA, which more closely resemble human diets, increase both HDL LDL, suggesting that CA may be responsible for the lowering HDL. Our aim was to examine potential mechanism Nontransgenic (NTg) C57BL mice apoA-I-transgenic (apoAI-Tg) greatly increased basal apoA-I levels, were used. Mice fed following four diets: control (C), (HF), 1% cholate (CA) + CA. Dietary reduced by 35% NTg 250% apoAI-Tg independent fat or cholesterol content diet. Hepatic mRNA decreased 30% 180% mice. synthesis transcription rates also parallel CA-induced decreases occurred primarily via decreasing rates. An 1.8-fold 1.5-fold Addition lowered 1.6-fold 2. 5-fold Transfection studies promoter suggested presence a putative cis-acting element CA-mediated down-regulation activity. Measurements regulatory protein-1 (ARP-1) mRNA, negative regulator gene mouse liver showed ARP-1 levels. Because alone not sufficient account scavenger receptor-B1 (SR-B1) hepatic lipase (HL) mRNAs quantitated. The SR-B1 HL changed These suggest regulates transcriptional bile response involving apoA-I, partly an unidentified post-transcriptional mechanism.