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丁酸通过增强肝线粒体功能缓解高脂诱导的小鼠肥胖
Butyrate Alleviates High Fat Diet-induced Obesity Through Enhancement of Mitochondrial Function in The Liver of Mice
【摘要】 丁酸可以预防高脂日粮诱导的小鼠肥胖和胰岛素抵抗,但是否有治疗作用尚不清楚。本研究证明,高脂日粮诱导小鼠肥胖模型后,用80 mg/mL丁酸钠水溶液灌胃能够缓解肥胖。表观指标检测发现,丁酸钠显著降低肥胖小鼠的肝重(1.24 g±0.03 g至1.08 g±0.04 g)、体重(32.46 g±0.50 g至28.35 g±0.58 g)和附睾脂重(1.33 g±0.13 g至0.81 g±0.08 g)及其与体重的比(4.06%±0.37%至2.83%±0.22%)。葡萄糖耐受实验和血液激素含量检测表明,丁酸钠部分缓解由高脂引起的葡萄糖不耐受,并显著降低血液中瘦素(3.71 ng/mL±0.62 ng/mL至1.50ng/m L±0.26 ng/mL)和胰岛素(2.39 ng/mL±0.30 ng/mL至1.25 ng/mL±0.09 ng/mL)的水平。肝中脂质和糖原的生化检测表明,丁酸钠对肝中的甘油三酯、胆固醇和糖原的含量没有显著影响。通过RT-PCR实验发现,丁酸钠显著上调线粒体β氧化和解耦联相关的关键基因以及线粒体自身编码的8个基因的mRNA水平的表达,Western印迹检测表明,丁酸钠显著升高肝葡萄糖转运蛋白GLUT2和调控线粒体功能的关键蛋白PGC-1α的表达。上述结果提示,丁酸钠可能通过增强肝线粒体功能缓解食源性小鼠肥胖。
【Abstract】 Butyrate can prevent high fat diet-induced obesity and insulin resistance in mice.However,whether butyrate has therapeutic effect on the treatment of obesity remains elusive.In this study,obese mice were prepared through feeding a high-fat diet with gavage administration,and then gavage with sodium butyrate(SB).The effect of alleviation on obesity by butyrate was observed.Results show that SB administration significantly reduced liver weight(1.24 g ± 0.03 g to 1.08 g ± 0.04 g),body weight(32.46 g ± 0.50 g to 28.35 g ± 0.58 g),epididymis fat(1.33 g ± 0.13 g to 0.81 g ± 0.08 g) and its index to body weight(4.06% ± 0.37% to 2.83% ± 0.22%).Results of glucose tolerance test indicate that SB alleviated high fat diet-induced glucose intolerance and the levels of leptin(3.71 ng/mL ± 0.62 ng/mL to 1.50 ng/mL ± 0.26 ng/mL) and insulin(2.39 ng/mL ± 0.30 ng/m L to 1.25 ng/m L ± 0.09 ng/m L) in plasma.However,there is no difference for the concentrations of triglyceride,cholesterol and glycogen in the liver.Moreover,SB significantly enhanced eight of all 13 mtDNA-encoded genes and up-regulated the mRNA expression levels of the key genes involved inmitochondrial thermogenesis and fatty acid β-oxidation in the liver.SB treatment also significantly increased the protein expression of glucose transporter 2 and peroxisome proliferator-activated receptor gamma coactivator-1 a in the liver.Taken together,our results indicate that short-term oral administration of SB can alleviate diet-induced obesity in mice through activation of mitochondrial function in the liver.
- 【文献出处】 中国生物化学与分子生物学报 ,Chinese Journal of Biochemistry and Molecular Biology , 编辑部邮箱 ,2017年12期
- 【分类号】R589.2
- 【被引频次】5
- 【下载频次】401