Amla prevents fructose-induced hepatic steatosis in ovariectomized rats: role of liver FXR and LXRα
Amla prevents fructose-induced hepatic steatosis in ovariectomized rats: role of liver FXR and LXRα
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DOI：
10.3109/13697137.2014.933408
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发表时间：
2015-04-01
期刊：
影响因子：
2.8
通讯作者：
Paulose, D. T.
中科院分区：
文献类型：
--
作者：
Koshy, S. M.;Bobby, Z.;Paulose, D. T.
目的增加果糖摄入量导致绝经后妇女血脂异常和脂肪肝，这两个独立的心血管疾病危险因素。在果糖喂养的绝经大鼠模型上，探讨余甘油降低高胆固醇血症、高甘油三酯血症、预防脂肪肝的可能机制。他们进一步被分成使用或不使用AMLA的组。结果治疗18周后，AMLA组大鼠肝组织中参与脂代谢的关键蛋白--肝法尼样X受体(FXR)和肝X受体(LXR)蛋白表达增加。果糖喂养的大鼠会患上脂肪肝，而AMLA可以预防这种情况。在这里，AMLA产生了LXR和胰岛素诱导基因-2(INSIG-2)的异常上升，这阻止了负责甘油三酯合成的固醇调节元件结合蛋白-1和固醇辅酶A去饱和酶-1的成熟。AMLA还增加了参与高密度脂蛋白(HDL)合成的ATP结合盒转运体A1(ABCA1)和负责摄取低密度脂蛋白胆固醇的低密度脂蛋白受体(LDLR)的蛋白表达。结论AMLA可增加肝脏FXR、LXRa、PPARa及其下游蛋白Insig-2、ABCA1和LDLR的蛋白表达。AMLA的这一特性可以调节一些与脂质代谢有关的关键蛋白，有望成为预防血脂异常和肝脏脂肪变性的有效药物。
Objectives Increased fructose consumption causes dyslipidemia and fatty liver in postmenopausal women, both independent risk factors for cardiovascular disease. This study explored the potential mechanisms by which amla(Emblica officinalis) reduced hypercholesterolemia and hypertriglyceridemia and prevented fatty liver in a fructose-fed, ovariectomized rat model of menopause.Methods Sham-operated and ovariectomized rats were put on a chow or high fructose diet. They were further divided into groups with or without amla. After 18 weeks of treatment, livers were harvested and subjected to Western blot and histological analyses.Results In all groups, amla increased the protein expression of liver farnesoid X receptor(FXR) and liver X receptor(LXR), key proteins involved in lipid metabolism. Fructose-fed rats developed fatty liver and amla prevented this. Here amla produced an exceptional rise in LXR and insulin-induced gene-2(Insig-2) which prevented the maturation of sterol regulatory element-binding protein-1 and steroyl CoA desaturase-1, responsible for triglyceride synthesis. Amla also increased the protein expression of ATP binding cassette transporter A1(ABCA1), involved in high density lipoprotein(HDL) synthesis as well as low density lipoprotein receptor (LDLR) responsible for uptake of LDL cholesterol. Besides this, amla increased the protein expression of peroxisome proliferator activated receptor a(PPAR a) involved in beta oxidation of fatty acids.Conclusions Amla increased the protein expression of liver FXR, LXR a, PPAR a and their downstream proteins Insig-2, ABCA1 and LDLR. This property of amla to modulate some of the key proteins involved in lipid metabolism promises its usefulness as a preventive agent for dyslipidemia and hepatic steatosis.