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海参中的膳食皂素通过 PPARα 和 SREBP-1c 信号通路缓解乳清酸诱导的大鼠脂肪肝。

Dietary saponins of sea cucumber alleviate orotic acid-induced fatty liver in rats via PPARalpha and SREBP-1c signaling.

机构信息

College of Food Science and Engineering, Ocean University of China, Qingdao, China.

出版信息

Lipids Health Dis. 2010 Mar 9;9:25. doi: 10.1186/1476-511X-9-25.

Abstract

BACKGROUND

Nonalcoholic fatty liver disease is the most common chronic liver disease in the world, and is becoming increasingly prevalent. Saponins of sea cucumber (SSC) are proven to exhibit various biological activities. Therefore, the present study was undertaken to examine the effect of saponins extracted from sea cucumber (Pearsonothuria graeffei) on the preventive activity of fatty liver in rats.

METHODS

Male Wistar rats were randomly divided into five groups, including normal control group, fatty liver model group, SSC-treated group with SSC at levels of 0.01%, 0.03% and 0.05%. Model rats were established by administration with 1% orotic acid (OA). After the experiment period, serum total cholesterol (TC), triglyceride (TG), and hepatic lipid concentrations were determined. To search for a possible mechanism, we examined the changes of key enzymes and transcriptional factors involved in hepatic lipids biosynthesis, fatty acid beta-oxidation.

RESULTS

Both 0.03% and 0.05% SSC treatment alleviated hepatic steatosis and reduced serum TG and TC concentration significantly in OA fed rats. Hepatic lipogenic enzymes, such as fatty acid synthase (FAS), malic enzyme (ME), and glucose-6-phosphate dehydrogenase (G6PDH) activities were inhibited by SSC treatment. SSC also decreased the gene expression of FAS, ME, G6PDH and sterol-regulatory element binding protein (SREBP-1c). Otherwise, the rats feeding with SSC showed increased carnitine palmitoyl transferase (CPT) activity in the liver. Hepatic peroxisome proliferator-activated receptor (PPARalpha), together with its target gene CPT and acyl-CoA oxidase (ACO) mRNA expression were also upregulated by SSC.

CONCLUSIONS

According to our study, the lipids-lowering effect of dietary SSC may be partly associated with the enhancement of beta-oxidation via PPARalpha activation. In addition, the inhibited SREBP-1c- mediated lipogenesis caused by SSC may also contribute to alleviating fatty liver.

摘要

背景

非酒精性脂肪性肝病是世界上最常见的慢性肝病,其发病率正在不断上升。海参皂苷已被证明具有多种生物活性。因此,本研究旨在探讨海参(糙海参)皂苷对大鼠脂肪肝预防活性的影响。

方法

雄性 Wistar 大鼠随机分为五组,包括正常对照组、脂肪肝模型组、海参皂苷处理组(海参皂苷浓度分别为 0.01%、0.03%和 0.05%)。模型大鼠给予 1%乳清酸(OA)。实验结束后,测定血清总胆固醇(TC)、甘油三酯(TG)和肝脂质浓度。为寻找可能的机制,我们检测了参与肝脂生物合成、脂肪酸β氧化的关键酶和转录因子的变化。

结果

0.03%和 0.05%的海参皂苷处理均可改善 OA 喂养大鼠的肝脂肪变性,并显著降低血清 TG 和 TC 浓度。肝生脂酶,如脂肪酸合酶(FAS)、苹果酸酶(ME)和葡萄糖-6-磷酸脱氢酶(G6PDH)的活性受到海参皂苷处理的抑制。海参皂苷还降低了 FAS、ME、G6PDH 和固醇调节元件结合蛋白-1c(SREBP-1c)的基因表达。此外,给予海参皂苷的大鼠肝肉毒碱棕榈酰转移酶(CPT)活性增加。肝过氧化物酶体增殖物激活受体(PPARalpha)及其靶基因 CPT 和酰基辅酶 A 氧化酶(ACO)mRNA 表达也被 SSC 上调。

结论

根据我们的研究,膳食中海参皂苷的降血脂作用可能部分与通过 PPARalpha 激活增强β氧化有关。此外,海参皂苷抑制 SREBP-1c 介导的脂生成也可能有助于缓解脂肪肝。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49a0/2846940/5b404550c8e4/1476-511X-9-25-1.jpg

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