Acharya Pooja, Talahalli Ramaprasad R
Department of Biochemistry, CSIR-Central Food Technological Research Institute, Mysore, 570020, Karnataka, India.
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, Uttar Pradesh, India.
Lipids. 2019 Jan;54(1):39-51. doi: 10.1002/lipd.12125. Epub 2019 Feb 10.
In this study, the effect of n-3 fatty acids (FA) [α-linolenic acid (ALA) and eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA)] on the intestinal bile acid (BA) uptake, hepatic BA synthesis, and enterohepatic bile acid transporters (BAT) was assessed in young and aged dyslipidemic rats. Dyslipidemia was induced in young and aged rats by feeding a high-fat (HF) diet. Experimental groups received diets containing canola oil (HF + CNO) and fish oil (HF + FO) as a source of ALA and EPA + DHA, respectively. After 60 days of feeding, intestinal BA uptake and expression of apical sodium-dependent bile acid transporter (Asbt), organic solute transporter-alpha/beta (Osta/b) messenger RNA (mRNA), and hepatic expression of Na taurocholate cotransporting polypeptide (Ntcp), bile salt export pump (Bsep), cholesterol 7-α hydroxylase A1 (Cyp7a1), Farnesoid X receptor (Fxr), small heterodimer partner-1 (Shp), liver receptor homolog-1 (Lrh-1), and hepatic nuclear factor-4 alpha (Hnf4a) mRNA were measured. Hepatic 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase activity and total BA in serum, liver, and feces were assessed. The dyslipidemic HF group had: (1) increased intestinal BA uptake and Asbt and Osta/b mRNA expression, (2) increased BA in serum, (3) decreased hepatic expression of Ntcp, Bsep, and Cyp7a1 mRNA, (4) increased activity of HMG-CoA reductase, (5) increased hepatic expression of Fxr and Shp mRNA, (6) decreased hepatic expression of Lrh-1 and Hnf4a mRNA, and (7) decreased BA in feces, when compared to control, HF + CNO, and HF + FO groups. Immunostaining revealed increased expression of intestinal Asbt and hepatic Ntcp protein in the HF group when compared to control, HF + CNO, and HF + FO groups. n-3 FA abrogated dyslipidemia-induced changes in the intestinal uptake, hepatic synthesis, and enterohepatic transporters of BA in both young and aged rats. EPA + DHA was more effective than ALA in modulating dyslipidemia-induced changes.
在本研究中，评估了n-3脂肪酸（FA）[α-亚麻酸（ALA）和二十碳五烯酸（EPA）+二十二碳六烯酸（DHA）]对年轻和老年血脂异常大鼠肠道胆汁酸（BA）摄取、肝脏BA合成以及肠肝胆汁酸转运体（BAT）的影响。通过喂食高脂（HF）饮食诱导年轻和老年大鼠发生血脂异常。实验组分别接受含有菜籽油（HF + CNO）和鱼油（HF + FO）作为ALA和EPA + DHA来源的饮食。喂食60天后，检测肠道BA摄取以及顶端钠依赖性胆汁酸转运体（Asbt）、有机溶质转运体α/β（Osta/b）信使核糖核酸（mRNA）的表达，以及肝脏中牛磺胆酸钠共转运多肽（Ntcp）、胆盐输出泵（Bsep）、胆固醇7-α羟化酶A1（Cyp7a1）、法尼醇X受体（Fxr）、小异源二聚体伴侣-1（Shp）、肝脏受体同源物-1（Lrh-1）和肝细胞核因子-4α（Hnf4a）mRNA的表达。评估肝脏3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶活性以及血清、肝脏和粪便中的总BA。与对照组、HF + CNO组和HF + FO组相比，血脂异常的HF组具有：（1）肠道BA摄取增加以及Asbt和Osta/b mRNA表达增加，（2）血清中BA增加，（3）肝脏中Ntcp、Bsep和Cyp7a1 mRNA表达降低，（4）HMG-CoA还原酶活性增加，（5）肝脏中Fxr和Shp mRNA表达增加，（6）肝脏中Lrh-1和Hnf4a mRNA表达降低，以及（7）粪便中BA降低。免疫染色显示，与对照组、HF + CNO组和HF + FO组相比，HF组肠道Asbt和肝脏Ntcp蛋白的表达增加。n-3 FA消除了年轻和老年大鼠血脂异常诱导的BA肠道摄取、肝脏合成以及肠肝转运体的变化。EPA + DHA在调节血脂异常诱导的变化方面比ALA更有效。
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