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荷叶水提取物通过调节PPARγ2表达降低高脂饮食诱导的肥胖大鼠的内脏脂肪量并改善胰岛素抵抗。

Lotus Leaf Aqueous Extract Reduces Visceral Fat Mass and Ameliorates Insulin Resistance in HFD-Induced Obese Rats by Regulating PPARγ2 Expression.

作者信息

Yan Kemin, Zhu Huijuan, Xu Jian, Pan Hui, Li Naishi, Wang Linjie, Yang Hongbo, Liu Meijuan, Gong FengYing

机构信息

Key Laboratory of Endocrinology of National Health and Family Planning Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical CollegeBeijing, China.

Department of Endocrinology, Beijing Tian Tan Hospital, Capital Medical UniversityBeijing, China.

出版信息

Front Pharmacol. 2017 Jun 23;8:409. doi: 10.3389/fphar.2017.00409. eCollection 2017.

Abstract

Lotus leaf is a kind of traditional Chinese medicine. We aimed to explore the effects of lotus leaf aqueous extract (LLAE) on peroxisome proliferative activated receptor γ2 (PPARγ2) expression in preadipocytes and adipocytes and further investigate its effects on high fat diet (HFD)-induced obese rats. pGL3-Enhancer-PPARγ2 (625 bp)-Luc plasmid, a luciferase reporter gene expression plasmid containing PPARγ2 promoter, was stably transfected into 3T3-L1 preadipocytes. PPARγ2 promoter activities were determined by assaying the luciferase activities. Then PPARγ2 promoter activities in preadipocytes and PPARγ2 mRNA levels in human subcutaneous adipocytes were measured after the administration with LLAE. Additionally, the effects of LLAE on body weight, fat mass, glucose and lipid metabolism and the expression of PPARγ2, insulin receptor substrate 1 and glucose transporter 4 (GLUT4) in visceral adipose tissue (VAT) were measured in HFD-induced obese rats treated with low or high dose [0.5 or 3.0 g crude drug/(kg.d)] LLAE for 6 weeks. Ten μg/ml LLAE significantly increased the luciferase activities in 3T3-L1 cells and the stimulatory action reached 2.51 folds of controls when LLAE was 1000 μg/ml ( < 0.01). After treating 3T3-L1 cells with 100 μg/ml LLAE, the stimulatory role peaked at 32 h where it was 2.58 folds of controls ( < 0.01). Besides, 100 μg/ml LLAE significantly increased PPARγ2 mRNA levels in human adipocytes to 1.91 folds of controls ( < 0.01). In HFD-induced obese rats, administration with both low and high dose LLAE notably reduced visceral fat mass by 45.5 and 58.4%, respectively, and significantly decreased fasting serum insulin levels ( < 0.05). The high dose LLAE also significantly decreased homeostasis model assessment of insulin resistance in obese rats ( < 0.05). Furthermore, the mRNA levels of PPARγ2 and GLUT4 in VAT of obese rats were significantly increased when compared with control rats, and were notably suppressed by LLAE intervention for 6 weeks ( < 0.05). LLAE significantly reduces visceral fat mass and ameliorates insulin resistance in HFD-induced obese rats. These beneficial effects of LLAE may associate with its role in stimulating PPARγ2 expression in preadipocytes and subcutaneous adipocytes and suppressing PPARγ2 and GLUT4 expression in VAT.

摘要

荷叶是一种传统中药。我们旨在探讨荷叶水提取物(LLAE)对前脂肪细胞和脂肪细胞中过氧化物酶体增殖激活受体γ2(PPARγ2)表达的影响,并进一步研究其对高脂饮食(HFD)诱导的肥胖大鼠的作用。将pGL3-增强子-PPARγ2(625 bp)-Luc质粒(一种含有PPARγ2启动子的荧光素酶报告基因表达质粒)稳定转染至3T3-L1前脂肪细胞中。通过检测荧光素酶活性来测定PPARγ2启动子活性。然后在给予LLAE后,测量前脂肪细胞中的PPARγ2启动子活性以及人皮下脂肪细胞中的PPARγ2 mRNA水平。此外,在以低剂量或高剂量[0.5或3.0 g生药/(kg·d)]LLAE处理6周的HFD诱导的肥胖大鼠中,测量LLAE对体重、脂肪量、葡萄糖和脂质代谢以及内脏脂肪组织(VAT)中PPARγ2、胰岛素受体底物1和葡萄糖转运蛋白4(GLUT4)表达的影响。10μg/ml的LLAE显著增加了3T3-L1细胞中的荧光素酶活性,当LLAE为1000μg/ml时,刺激作用达到对照的2.51倍(P<0.01)。用100μg/ml LLAE处理3T3-L1细胞后,刺激作用在32小时达到峰值,为对照的2.58倍(P<0.01)。此外,100μg/ml LLAE显著将人脂肪细胞中的PPARγ2 mRNA水平提高至对照的1.91倍(P<0.01)。在HFD诱导的肥胖大鼠中,低剂量和高剂量LLAE给药均显著降低了内脏脂肪量,分别降低了45.5%和58.4%,并显著降低了空腹血清胰岛素水平(P<0.05)。高剂量LLAE还显著降低了肥胖大鼠的胰岛素抵抗稳态模型评估值(P<0.05)。此外,与对照大鼠相比,肥胖大鼠VAT中PPARγ2和GLUT4的mRNA水平显著升高,而在LLAE干预6周后显著受到抑制(P<0.05)。LLAE显著降低HFD诱导的肥胖大鼠的内脏脂肪量并改善胰岛素抵抗。LLAE的这些有益作用可能与其刺激前脂肪细胞和皮下脂肪细胞中PPARγ2表达以及抑制VAT中PPARγ2和GLUT4表达的作用有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58d2/5481353/412e32b9187a/fphar-08-00409-g001.jpg

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