Approach to metabolic syndrome by analysing the energy metabolism homeostasis

通过分析能量代谢稳态来研究代谢综合征

• 批准号: 20580103
• 负责人: WATANABE Mitsuhiro
• 金额: $ 3.08万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20580103/
• 关键词: 代謝; 糖尿病; 胆汁酸; 核内受容体; 生活習慣病; エネルギー代謝; オミックス解析

Administration of FXR agonist accentuated body weight gain and glucose intolerance induced by the high fat diet and led to a pronounced worsening of the changes in liver and adipose tissue. Mechanistically, treatment with FXR agonist decreased BA biosynthesis, BA pool size and energy expenditure. Our data hence suggest that activation of FXR with synthetic agonists is not useful for long term management of the metabolic syndrome, as it reduces the BA pool size and subsequently decreases energy expenditure, translating in weight gain and insulin resistance. In addition, it was suggested that bile acid participated in amino acid metabolism in energy homeostasis by DNA micro array and metabolome analysis.

FXR激动剂的施用加剧了高脂肪饮食引起的体重增加和葡萄糖不耐受，并导致肝脏和脂肪组织的变化明显恶化。从机制上讲，FXR 激动剂治疗降低了 BA 生物合成、BA 池大小和能量消耗。因此，我们的数据表明，用合成激动剂激活 FXR 对于代谢综合征的长期管理并无帮助，因为它会减少 BA 池的大小，从而减少能量消耗，从而导致体重增加和胰岛素抵抗。此外，DNA微阵列和代谢组分析表明，胆汁酸参与能量稳态的氨基酸代谢。

项目成果

Lowering bile acid pool size with an FXR agonist induces obesity and diabetes through the decrease of energy expenditure.

使用 FXR 激动剂降低胆汁酸池大小可通过减少能量消耗诱发肥胖和糖尿病。

• 发表时间: 2010
• 作者: Borjihan B;Ogita A;Fujita KI;Doe M;Tanaka T;Yuki Kondo;渡辺光博
• 通讯作者: 渡辺光博

Influence of FXR activation in the metabolic control

FXR 激活对代谢控制的影响

• 发表时间: 2009
• 作者: 畠山智充;神矢拓朗;平林淳;郷田秀一郎;海野英昭;渡辺光博
• 通讯作者: 渡辺光博

胆汁酸による甲状腺ホルモン代謝調節

胆汁酸对甲状腺激素代谢的调节

• 发表时间: 2010
• 作者: 渡辺光博

Decreasing bile acid synthesis with an FXR agonist induces obesity and diabetes through the decrease of energy expenditure

使用 FXR 激动剂减少胆汁酸合成可通过减少能量消耗诱发肥胖和糖尿病

• 发表时间: 2010
• 作者: Aburai N.;Yoshida M.;Ohnishi M.;Kimura K.;渡辺光博
• 通讯作者: 渡辺光博

胆汁酸による糖・エネルギー代謝

胆汁酸的糖和能量代谢

• 发表时间: 2010
• 作者: H. Hamada;K. Shimoda;N. Nakajima;et. al.;渡辺光博
• 通讯作者: 渡辺光博