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黄连素改善非酒精性脂肪性肝病中的糖异生和脂质代谢。

Berberine improves glucogenesis and lipid metabolism in nonalcoholic fatty liver disease.

作者信息

Zhao Li, Cang Zhen, Sun Honglin, Nie Xiaomin, Wang Ningjian, Lu Yingli

机构信息

Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital Affiliated to Shanghai JiaoTong University School of Medicine, Shanghai, 200011, China.

出版信息

BMC Endocr Disord. 2017 Feb 28;17(1):13. doi: 10.1186/s12902-017-0165-7.

Abstract

BACKGROUND

Nonalcoholic fatty liver disease (NAFLD) is considered a critical hepatic manifestation of metabolic syndrome. Berberine (BBR) exerts anti-hyperglycemic and anti-dyslipidemic effects and can also ameliorate NAFLD. Thus, BBR might exert its therapeutic effect on NAFLD by improving glucolipid metabolism. Here, we investigated the aspects and extent to which glucolipid metabolism were affected by BBR in rats with NAFLD.

METHODS

Three groups of Sprague-Dawley rats were studied: a control group (n = 6) fed a normal chow diet and a NAFLD group (n = 6) and a NAFLD + BBR group (n = 6) fed a high-fat diet. Normal saline and BBR (150 mg/kg body weight/day for 16 weeks) were administered by gavage. All rats were infused with isotope tracers. The rates of glucose appearance (Ra), gluconeogenesis (GNG) and glycerol appearance (Ra) were assessed with H and C tracers, whereas the rates of hepatic lipogenesis and fatty acid β oxidation were measured using the H tracer.

RESULTS

When the NAFLD model was successfully induced by administering a high-fat diet, body weight, insulin resistance and dyslipidemia were significantly increased. After the BBR treatment, weight loss, decreased lipid profiles and HOMA-IR, and increased ISI were observed. Meanwhile, BBR reduced Ra, GNG and hepatic lipogenesis, whereas the rate of fatty acid β oxidation in skeletal muscle showed an increasing trend. Ra showed a decreasing trend. Based on the results of the histological analysis, BBR obviously attenuated the ectopic liver fat accumulation.

CONCLUSIONS

BBR improved NAFLD by inhibiting glucogenesis and comprehensively regulating lipid metabolism, and its effect on inhibiting hepatic lipogenesis was much stronger. The improvement may be partly mediated by weight loss. Berberine might be a good choice for patients with NAFLD and glucose metabolic disorder. Future clinical trials need to be conducted to confirm these effects.

摘要

背景

非酒精性脂肪性肝病(NAFLD)被认为是代谢综合征的一种关键肝脏表现。黄连素(BBR)具有降血糖和降血脂作用,还可改善NAFLD。因此,BBR可能通过改善糖脂代谢对NAFLD发挥治疗作用。在此,我们研究了BBR对NAFLD大鼠糖脂代谢影响的方面和程度。

方法

研究了三组斯普拉格-道利大鼠:对照组(n = 6)给予正常饲料饮食,NAFLD组(n = 6)和NAFLD + BBR组(n = 6)给予高脂饮食。通过灌胃给予生理盐水和BBR(150 mg/kg体重/天,共16周)。所有大鼠均注入同位素示踪剂。用氢和碳示踪剂评估葡萄糖生成率(Ra)、糖异生(GNG)和甘油生成率(Ra),而用氢示踪剂测量肝脏脂肪生成率和脂肪酸β氧化率。

结果

通过给予高脂饮食成功诱导NAFLD模型后,体重、胰岛素抵抗和血脂异常显著增加。BBR治疗后,观察到体重减轻、血脂谱和HOMA-IR降低以及ISI增加。同时,BBR降低了Ra、GNG和肝脏脂肪生成,而骨骼肌中脂肪酸β氧化率呈上升趋势。Ra呈下降趋势。基于组织学分析结果,BBR明显减轻了肝脏异位脂肪堆积。

结论

BBR通过抑制糖异生和全面调节脂质代谢改善NAFLD,其对抑制肝脏脂肪生成的作用更强。这种改善可能部分由体重减轻介导。黄连素可能是NAFLD和糖代谢紊乱患者的一个良好选择。未来需要进行临床试验来证实这些作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30ac/5329945/07ab0558bf26/12902_2017_165_Fig1_HTML.jpg

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