Diabetologia:糙米特异性γ-谷维素对高脂肪饮食诱导的肥胖症小鼠脑纹状体中多巴胺D2受体表观遗传调节的影响

2017-07-31 MedSci MedSci原创

过量脂肪饮食会导致人类和啮齿类动物的肥胖。最近在人类和啮齿动物方面的研究表明,对食用脂肪成瘾与酗酒,尼古丁和麻醉药物成瘾有着共同的机制:大脑功能系统紊乱。已经强调,高脂肪饮食(HFD)减弱纹状体中的多巴胺D2受体(D2R)信号,这是脑回报系统的关键调节剂,导致享受暴饮暴食。研究人员以前报告说,糙米特异性生物活性成分γ-谷维素通过下丘脑控制减弱了HFD的偏好。因此,探讨了γ-谷维素可以调节小鼠脑回报

近日,国际杂志 《Diabetologia》上在线发表一项关于糙米特异性γ-谷维素对高脂肪饮食诱导的肥胖症小鼠脑纹状体中多巴胺D2受体表观遗传调节的影响的研究。

过量脂肪饮食会导致人类和啮齿类动物的肥胖。最近在人类和啮齿动物方面的研究表明,对食用脂肪成瘾与酗酒,尼古丁和麻醉药物成瘾有着共同的机制:大脑功能系统紊乱。已经强调,高脂肪饮食(HFD)减弱纹状体中的多巴胺D2受体(D2R)信号,这是脑回报系统的关键调节剂,导致享受暴饮暴食。研究人员以前报告说,糙米特异性生物活性成分γ-谷维素通过下丘脑控制减弱了HFD的偏好。因此,探讨了γ-谷维素可以调节小鼠脑回报系统功能的可能性。

喂食HFD的雄性C57BL/6J小鼠用γ-谷维素口服治疗,并评估参与D2R信号传导的分子的纹状体水平。检查了γ-谷维素对D2R启动子的DNA甲基化的影响以及随后膳食脂肪偏好的变化。此外,还研究了5-甲基-2'-脱氧胞苷(DNA甲基转移酶(DNMTs)的有效抑制剂)对食物偏好,D2R信号和纹状体DNMT水平的影响。在体外酶法评估了γ-谷维素对DNMT活性的抑制作用。

在喂食HFD的小鼠的纹状体中,D2R的产生通过D2R的启动子区域的DNA甲基化的增加而降低。口服γ-谷维素降低DNMTs的表达和活性,从而恢复纹状体中D2R的水平。5-氮杂-2'-脱氧胞苷对DNMTs的药理学抑制也改善了对膳食脂肪的偏好。与这些发现一致,酶体外测定显示γ-谷维素能够抑制DNMTs的活性。

研究证明,γ-谷维素改善了小鼠纹状体中D2R启动子区域的HFD诱导的DNA超甲基化。研究实验范例因γ-谷维素具有作为新颖表观遗传调节剂的独特性质可将作为一种有希望的抗肥胖物质。

原始出处:

Chisayo Kozuka, Tadashi Kaname, Chigusa Shimizu-Okabe,et al. Impact of brown rice-specific γ-oryzanol on epigenetic modulation of dopamine D2 receptors in brain striatum in high-fat-diet-induced obesity in mice

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    2017-08-02 pcw111
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    2017-08-01 189****7206

    学习了受益匪浅

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