Anti-obesity and anti-hyperglycemic effects of the dietary citrus limonoid nomilin in mice fed a high-fat diet
Anti-obesity and anti-hyperglycemic effects of the dietary citrus limonoid nomilin in mice fed a high-fat diet
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DOI：
10.1016/j.bbrc.2011.06.055
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发表时间：
2011-07-08
影响因子：
3.1
通讯作者：
Sato, Ryuichiro
中科院分区：
文献类型：
--
作者：
Ono, Eri;Inoue, Jun;Sato, Ryuichiro
TGR 5是G蛋白偶联受体家族的成员，并被胆汁酸（BA）激活。TGR 5被认为是代谢性疾病的一个有前途的药物靶点，因为TGR 5的激活可以预防高脂饮食（HFD）小鼠的肥胖和高血糖症。在本研究中，我们确定了一种天然存在的柠檬苦素，nomilin，作为TGR 5的激活剂。与BA不同，诺米林没有表现出法尼醇X受体配体活性。虽然诺米林衍生物obacunone能够激活TGR 5，但柠檬苦素（柑橘种子中最丰富的柠檬苦素）不是TGR 5激活剂。当喂食HFD 9周的雄性C57 BL/6 J小鼠进一步喂食单独的HFD或补充有0.2%w/w诺米林的HFD 77天时，诺米林处理的小鼠具有较低的体重、血清葡萄糖、血清胰岛素和增强的葡萄糖耐量。我们的研究结果表明，诺米林作为一种具有抗肥胖和抗高血糖作用的药物，可能是通过激活TGR 5介导的一种新的生物学功能。(C)2011 Elsevier Inc. All rights reserved.
TGR5 is a member of the G protein-coupled receptor family and is activated by bile acids (BAs). TGR5 is thought to be a promising drug target for metabolic diseases because the activation of TGR5 prevents obesity and hyperglycemia in mice fed a high-fat diet (HFD). In the present study, we identified a naturally occurring limonoid, nomilin, as an activator of TGR5. Unlike BAs, nomilin did not exhibit the farnesoid X receptor ligand activity. Although the nomilin derivative obacunone was capable of activating TGR5, limonin (the most abundant limonoid in citrus seeds) was not a TGR5 activator. When male C57BL/6J mice fed a HFD for 9 weeks were further fed a HFD either alone or supplemented with 0.2% w/w nomilin for 77 days, nomilin-treated mice had lower body weight, serum glucose, serum insulin, and enhanced glucose tolerance. Our results suggest a novel biological function of nomilin as an agent having anti-obesity and anti-hyperglycemic effects that are likely to be mediated through the activation of TGR5. (C) 2011 Elsevier Inc. All rights reserved.