کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8538998 | 1561124 | 2018 | 39 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Activation of PPARα decreases bile acids in livers of female mice while maintaining bile flow and biliary bile acid excretion
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
BAATOATPNtcpNPC1L1FXRSecondary bile acidsBSEPBALunconjugated bile acidsPPARαClofSHPFGFMCAfarnesoid X receptor - Farnesoid X گیرندهUPLC-MS/MS - UPLC-MS / MSAsbt - آزبستBile acid - اسید صفراویmuricholic acid - اسید چربCholic acid - اسید چلیکBile acids - اسیدهای صفراویtotal bile acids - اسیدهای صفراوی کلOst - اورتapical sodium-dependent bile acid transporter - اپوکسی سدیم وابسته به پروتئین اسید صفراGender difference - تفاوت جنسیتیOat - جو دو سرorganic anion transporter - حمل کننده آنیون آلیBiliary excretion - دفع ادرارorganic solute transporter - رقیق کننده ارگانیکsmall heterodimer partner - شرکای کوچک همجنسگراfibroblast growth factor - فاکتور رشد فیبروبلاستOrganic anion transporting polypeptide - پلیپپتید حمل آنیون ارگانیکBile salt export pump - پمپ صادرات نمک صفرclofibrate - کلافیبرتperoxisome proliferator-activated receptor α - گیرنده پروتئینی فعال پروکسایزوم α
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Fibrates are hypolipidemic drugs that act as activators of peroxisome proliferator-activated receptor α (PPARα). In both humans and rodents, females were reported to be less responsive to fibrates than males. Previous studies on fibrates and PPARα usually involved male mice, but little has been done in females. The present study aimed to provide the first comprehensive analysis of the effects of clofibrate (CLOF) and PPARα on bile acid (BA) homeostasis in female mice. Study in WT male mice showed that a 4-day CLOF treatment increased liver weight, bile flow, and biliary BA excretion, but decreased total BAs in both serum and liver. In contrast, WT female mice were less susceptible to these CLOF-mediated responses observed in males. In WT female mice, CLOF decreased total BAs in the liver, but had little effect on the mRNAs of hepatic BA-related genes. Next, a comparative analysis between WT and PPARα-null female mice showed that lack of PPARα in female mice decreased total BAs in serum, but had little effect on total BAs in liver or bile. However, lack of PPARα in female mice increased mRNAs of BA synthetic enzymes (Cyp7a1, Cyp8b1, Cyp27a1, and Cyp7b1) and transporters (Ntcp, Oatp1a1, Oatp1b2, and Mrp3). Furthermore, the increase of Cyp7a1 in PPARα-null female mice was associated with an increase in liver Fxr-Shp-Lrh-1 signaling. In conclusion, female mice are resistant to CLOF-mediated effects on BA metabolism observed in males, which could be attributed to PPARα-mediated suppression in females on genes involved in BA synthesis and transport.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology and Applied Pharmacology - Volume 338, 1 January 2018, Pages 112-123
Journal: Toxicology and Applied Pharmacology - Volume 338, 1 January 2018, Pages 112-123
نویسندگان
Youcai Zhang, Andrew J. Lickteig, Iván L. Csanaky, Curtis D. Klaassen,