کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9886457 | 1537826 | 2005 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The ACAT inhibitor avasimibe increases the fractional clearance rate of postprandial triglyceride-rich lipoproteins in miniature pigs
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کلمات کلیدی
HDLHMG-CoAFCRACATRetinyl palmitateLPLLRPHSPGLDL receptor related protein3-hydroxy-3-methylglutaryl coenzyme A - 3 هیدروکسی 3-متیل گلوتاریل کوآنزیم AAUC - AUCapo - آپوapolipoprotein - آپولیپوپروتئینendoplasmic reticulum - شبکه آندوپلاسمی Lipoprotein lipase - لیپو پروتئین لیپازhigh density lipoprotein - لیپوپروتئین با چگالی بالاlow density lipoprotein - لیپوپروتئین چگالی کمLDL - لیپوپروتئین کم چگالی(کلسترول بد)area under the curve - منطقه تحت منحنیheparan sulfate proteoglycans - پروپوگلیکان های سولفات heparanhigh performance liquid chromatography - کروماتوگرافی مایع با کارایی بالاHPLC - کروماتوگرافی مایعی کارا
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Previously, we have shown, in vivo, that the acyl coenzyme A: cholesterol acyltransferase (ACAT) inhibitor avasimibe decreases hepatic apolipoprotein (apo) B secretion into plasma. To test the hypothesis that avasimibe modulates postprandial triglyceride-rich lipoprotein (TRL) metabolism in vivo, an oral fat load (2 g fat/kg) containing retinol was given to 9 control miniature pigs and to 9 animals after 28 days treatment with avasimibe (10 mg/kg/day, n = 5; 25 mg/kg/day, n = 4). The kinetic parameters for plasma retinyl palmitate (RP) metabolism were determined by multi-compartmental modeling using SAAM II. Avasimibe decreased the 2-h TRL (d < 1.006 g/mL; Sf > 20) triglyceride concentrations by 34%. The TRL triglyceride 0-12 h area under the curve (AUC) was decreased by 21%. In contrast, avasimibe had no effect on peak TRL RP concentrations, time to peak, or its rate of appearance into plasma, however, the TRL RP 0-12 h AUC was decreased by 17%. Analysis of the RP kinetic parameters revealed that the TRL fractional clearance rate (FCR) was increased 1.4-fold with avasimibe. The TRL RP FCR was negatively correlated with very low density lipoprotein (VLDL) apoB production rate measured in the fasting state (r = â0.504). No significant changes in total intestinal lipid concentrations were observed. Thus, although avasimibe had no effect on intestinal TRL secretion, plasma TRL clearance was significantly increased; an effect that may relate to a decreased competition with hepatic VLDL for removal processes.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids - Volume 1738, Issues 1â3, 30 December 2005, Pages 10-18
Journal: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids - Volume 1738, Issues 1â3, 30 December 2005, Pages 10-18
نویسندگان
John R. Burnett, Dawn E. Telford, P. Hugh R. Barrett, Murray W. Huff,