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阿拉伯茶(巧茶)上调雄性肥胖小鼠(C57BL/6J)白色脂肪组织中的脂肪分解基因。

Khat (Catha edulis) upregulates lipolytic genes in white adipose tissue of male obese mice (C57BL/6J).

机构信息

Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia; Division of Biomedical Sciences, School of Pharmacy, Faculty of Science & Engineering, University of Nottingham Malaysia Campus, Jalan Broga, 43500, Semenyih, Selangor, Malaysia.

Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.

出版信息

J Ethnopharmacol. 2020 Nov 15;262:113187. doi: 10.1016/j.jep.2020.113187. Epub 2020 Jul 27.

DOI:10.1016/j.jep.2020.113187
PMID:32730892
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Khat (Catha edulis (Vahl) Forssk.) is a herb from the Celastraceae family (also known as qat, gaad, or mirra) that is widely-consumed in East Africa and in the Arabian peninsula. The green leaves and small stems are consumed primarily at recreational and social gatherings, and medicinally for their antidiabetic and appetite-suppression effects.

AIMS

The objectives of this study were to determine the effects of khat and its active alkaloid, cathinone, on food intake and body weight in mice maintained on a high-fat diet, and to investigate its mechanism of action in white adipose tissue and in the hypothalamus.

MATERIALS & METHOD: Adult male mice (C57BL/6J) were fed a high fat diet (HFD) for 8 weeks (n = 30), then divided into 5 groups and treated daily for a further 8 weeks with HFD + vehicle [control (HFD)], HFD + 15 mg/kg orlistat (HFDO), HFD + 200 mg/kg khat extract (HFDK200), HFD + 400 mg/kg khat extract (HFDK400) and HFD + 3.2 mg/kg cathinone (HFDCAT). Treatments were carried out once daily by gastric gavage. Blood and tissue samples were collected for biochemical, hormonal and gene expression analyses.

RESULTS

Khat extracts and orlistat treatment significantly reduced weight gain as compared to control mice on HFD, and cathinone administration completely prevented weight gain in mice fed on HFD. Khat treatment caused a marked reduction in body fat and in serum triglycerides. A dose-dependent effect of khat was observed in reducing serum leptin concentrations. Analysis of gene expression in adipose tissue revealed a significant upregulation of two lipolysis pathway genes:(adipose triglyceride lipase (PNPLA-2) and hormone-sensitive lipase (LIPE). In the hypothalamic there was a significant (P < 0.05) upregulation of agouti-related peptide (AgRP) and cocaine-amphetamine regulated transcript (CART) genes in the HFDK400 and HFDCAT groups.

CONCLUSION

Cathinone treatment blocked body weight gain, while high dose khat extract significantly reduced the weight gain of mice on an obesogenic diet through stimulation of lipolysis in white adipose tissue.

摘要

民族药理学相关性

阿拉伯茶(育亨宾树)是卫矛科植物(也称为 qat、gaad 或 mirra)的一种草药,广泛存在于东非和阿拉伯半岛。绿色的叶子和小茎主要在娱乐和社交聚会上被食用,也用于治疗糖尿病和抑制食欲。

目的

本研究旨在确定阿拉伯茶及其活性生物碱卡西酮对高脂肪饮食喂养的小鼠的摄食量和体重的影响,并研究其在白色脂肪组织和下丘脑中的作用机制。

材料与方法

成年雄性小鼠(C57BL/6J)高脂饮食喂养 8 周(n=30),然后分为 5 组,再用高脂饮食+载体[对照(HFD)]、高脂饮食+15mg/kg 奥利司他(HFDO)、高脂饮食+200mg/kg 阿拉伯茶提取物(HFDK200)、高脂饮食+400mg/kg 阿拉伯茶提取物(HFDK400)和高脂饮食+3.2mg/kg 卡西酮(HFDCAT)每日治疗 8 周。治疗通过胃灌胃进行。收集血液和组织样本进行生化、激素和基因表达分析。

结果

与高脂肪饮食对照组相比,阿拉伯茶提取物和奥利司他治疗显著减少了体重增加,而卡西酮给药完全阻止了高脂肪饮食喂养的小鼠体重增加。阿拉伯茶治疗导致体脂和血清甘油三酯明显减少。阿拉伯茶在降低血清瘦素浓度方面表现出剂量依赖性作用。脂肪组织基因表达分析显示,两种脂肪分解途径基因(脂肪甘油三酯脂肪酶(PNPLA-2)和激素敏感脂肪酶(LIPE)显著上调。在下丘脑,高脂肪饮食喂养的 HFDK400 和 HFDCAT 组的 AgRP 和可卡因-安非他命调节转录物(CART)基因显著上调(P<0.05)。

结论

卡西酮治疗阻止了体重增加,而高剂量阿拉伯茶提取物通过刺激白色脂肪组织中的脂肪分解显著减少了肥胖饮食喂养的小鼠的体重增加。

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