Chinese medicine Jiangzhuo mixture regulates glucose and lipid metabolism in obese rats through TLR4/IκBα/NF-κB signaling pathway.

Qiong Su, Danna Jiang, Zhao Zhong, Kai Zhou, Wenbo Gong
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Abstract

Objectives: To explore the mechanism of Chinese medicine Jiangzhuo mixture regulating glucose and lipid metabolism in obese rats.

Methods: Thirty healthy male SD rats were randomly divided into normal control group, model control group, and Jiangzhuo mixture treatment group, with 10 rats in each group. The rats in the normal control group were fed with normal diet, the obesity model was induced by feeding high-fat diet in the model control group and the Jiangzhuo mixture treatment group, the rats in the treatment group were given with Jiangzhuo mixture 50 g/kg by gavage. After 8 weeks of intervention, the blood glucose (GLU), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels were measured in the three groups. Quantitative reverse transcription PCR were used to detect the expression levels of PR domain containing 16 (PRDM16) and uncoupling protein 1 (UCP1) in white and brown adipose tissues of the rats in each group; Western blotting was used to detect the expression of PRDM16 in the white and brown adipose tissue of rats, and Toll-like receptor 4 (TLR4), nuclear factor-κB (NF-κB) and inhibitor of NF-κB alpha (IκBα) in the white adipose tissue; immunohistochemistry was used to detect the expression of UCP1 protein in white and brown adipose tissues.

Results: Compared with the normal control group, the white fat weight (P<0.01), white fat coefficient (P<0.05) and Lee's coefficient (P<0.01) were significantly increased in the model control group; the contents of GLU, TC, TG and LDL-C were all increased, and the content of TG was significantly increased (P<0.05) in the model control group. The mRNA and protein expression levels of PRDM16 and UCP1 in white fat and brown fat were significantly decreased (P<0.05) in the model control group. Compared with the model control group, the white fat weight and white fat coefficient and Lee's coefficient were significantly reduced in the Jiangzhuo mixture treatment group (all P<0.01), the levels of GLU, TC, TG, and LDL-C in the the treatment group were all reduced, and the content of TG was reduced more obviously (P<0.01); expression levels of PRDM16 and UCP1 mRNA and protein were increased in brown and white adipose tissue. Compared with the normal control group, the expression levels of TLR4, phospho-IκBα and NF-κB-p65 proteins in white adipose tissue of the model control group were significantly increased (all P<0.01), while the expression levels of these proteins in the treatment group were significantly lower than those in the model control group (all P<0.05).

Conclusions: Jiangzhuo mixture can alleviate high-fat diet-induced increase in body fat, abnormal expression of biochemical indexes and promote the expression of key proteins including UCP1 and PRDM16 in white and brown adipose tissues by regulating TLR4/IκBα/NF-κB signaling pathway.

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降浊合剂通过TLR4/IκBα/NF-κB信号通路调节肥胖大鼠糖脂代谢。
目的:探讨中药降浊合剂调节肥胖大鼠糖脂代谢的机制。方法:健康雄性SD大鼠30只,随机分为正常对照组、模型对照组和降浊合剂治疗组,每组10只。正常对照组大鼠采用正常饮食喂养,模型对照组和降浊合剂治疗组采用高脂饮食诱导肥胖模型,治疗组大鼠灌胃给予降浊合剂50g/kg。干预8周后,测量三组患者的血糖(GLU)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白蛋白胆固醇(HDL-C)水平。定量逆转录聚合酶链式反应检测各组大鼠白色和棕色脂肪组织中PR结构域含16(PRDM16)和解偶联蛋白1(UCP1)的表达水平;采用蛋白质印迹法检测PRDM16在大鼠白色和棕色脂肪组织中的表达,以及Toll样受体4(TLR4)、核因子-κB(NF-κB)和NF-κB-α抑制剂(IκBα)在白色脂肪组织中表达;用免疫组织化学方法检测UCP1蛋白在白色和棕色脂肪组织中的表达。结果:与正常对照组相比,白色脂肪重量(PPPPPPPP结论:降浊合剂可通过调节TLR4/IκBα/NF-κB信号通路,减轻高脂饮食诱导的白色和棕色脂肪组织体脂增加、生化指标异常表达,并促进UCP1和PRDM16等关键蛋白的表达。
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