Unraveling liver-derived signals against obesity and diabetes

解开针对肥胖和糖尿病的肝源信号

• 批准号: 18390267
• 负责人: KATAGIRI Hideki
• 金额: $ 11.13万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18390267/
• 关键词: diabetes; metabolic syndrome; obesity

Metabolism is coordinated and regulated among different organs/tissues throughout the body. This coordinated metabolic regulation is apparently essential for maintaining systemic homeostasis, particularly glucose and energy metabolism. Therefore, communication among organs/tissues is extremely important and perturbation of this control system may lead to the development of metabolic disorders. During this decade, the versatility of adipose tissue as an endocrine organ and as a contributor to disease development has been established. However, a number of recent studies have shown that tissue-specific knockout mice exhibit unexpected phenotypes, suggesting the presence of many as yet unknown forms of cross-talk among organs/tissues.We have identified several systems consisting of autonomic nerve circuits, i.e. metabolic information highways, which play important roles in conveying inter-organ communication regarding metabolism. This is exemplified by the discovery of involvement of the afferent hepatic vagus in energy expenditure and fat accumulation. We expressed PPAR_γ in the liver, resulting in enhanced lipolysis in fat tissue and increased systemic energy expenditure. Thus, in response to lipid accumulation in the liver, hepatic vagal afferents transmit information regarding excess energy accumulation to the brain, thereby increasing sympathetic outflow to enhance energy expenditure.Our findings indicate that the brain obtains a variety of metabolic information from peripheral organs/tissues, resulting in cooperative metabolic regulation among tissues/organs throughout the body. Furthermore, these systems appear to contribute to pathological features of the metabolic syndrome under the condition of long-term excess calorie intake. Thus, elucidation of these regulatory systems may facilitate unraveling the mechanisms underlying metabolic homeostasis and those underlying development of the metabolic syndrome.

代谢在整个身体的不同器官/组织之间协调和调节。这种协调的代谢调节对于维持全身稳态，特别是葡萄糖和能量代谢，显然是必不可少的。因此，器官/组织之间的通信是极其重要的，并且该控制系统的扰动可能导致代谢紊乱的发展。在这十年中，脂肪组织作为内分泌器官和作为疾病发展的贡献者的多功能性已经被确立。然而，最近的一些研究表明，组织特异性基因敲除小鼠表现出意想不到的表型，这表明器官/组织之间存在许多未知形式的串扰。我们已经确定了几个由自主神经回路组成的系统，即代谢信息高速公路，它在传递器官间关于代谢的通信中起着重要作用。这通过发现肝迷走神经传入参与能量消耗和脂肪积累来例证。我们在肝脏中表达了过氧化物酶体增殖物激活受体γ，导致脂肪组织中脂肪分解的增强和全身能量消耗的增加。因此，在响应肝脏中的脂质积累，肝迷走神经传入传递信息，关于多余的能量积累到大脑，从而增加交感神经流出，以提高能源expenditure. We的研究结果表明，大脑获得各种代谢信息，从周围器官/组织，导致整个身体的组织/器官之间的合作代谢调节。此外，这些系统似乎有助于代谢综合征的病理特征的条件下，长期过量的热量摄入。因此，阐明这些调控系统可能有助于阐明代谢稳态的机制和代谢综合征的发展。

项目成果

Inter-organ Communication via Autonomic Nervous System Involved in Coordinated Metabolic Regulation

通过参与协调代谢调节的自主神经系统进行器官间通讯

• 发表时间: 2007
• 作者: Takei;D.;Ishihara;H.;Yamaguchi;S.;Yamada;T.;Katagiri;H.;Maruyama;Y.;Oka Y;片桐秀樹;Katagiri H;片桐秀樹;片桐秀樹;Katagiri H;片桐秀樹;Katagiri H
• 通讯作者: Katagiri H

Metabolic Information Highway〜メタボリックシンドローム研究の新展開〜

代谢信息高速公路～代谢综合征研究新进展～

• 发表时间: 2007
• 作者: Takei;D.;Ishihara;H.;Yamaguchi;S.;Yamada;T.;Katagiri;H.;Maruyama;Y.;Oka Y;片桐秀樹;Katagiri H;片桐秀樹;片桐秀樹;Katagiri H;片桐秀樹;Katagiri H;片桐秀樹;片桐秀樹;Katagiri H;片桐秀樹
• 通讯作者: 片桐秀樹

臓器間情報ネットワークによる糖・エネルギー代謝の協調的調節

通过器官间信息网络协调调节糖和能量代谢

• 发表时间: 2007
• 作者: Takei;D.;Ishihara;H.;Yamaguchi;S.;Yamada;T.;Katagiri;H.;Maruyama;Y.;Oka Y;片桐秀樹;Katagiri H;片桐秀樹;片桐秀樹;Katagiri H;片桐秀樹;Katagiri H;片桐秀樹;片桐秀樹;Katagiri H;片桐秀樹;Katagiri H;片桐秀樹;Katagiri H;片桐秀樹;Katagiri H;片桐秀樹;Katagiri H;片桐秀樹
• 通讯作者: 片桐秀樹

Signals from intra-abdominal fat modulate insulin and leptin sensitivity through different mechanisms: neuronal involvement in food-intake regulation.

• DOI: 10.1016/j.cmet.2006.02.001
• 发表时间: 2006-03
• 期刊: Cell metabolism
• 影响因子: 29
• 作者: Tetsuya Yamada;H. Katagiri;Y. Ishigaki;T. Ogihara;Junta Imai;Kenji Uno;Yutaka Hasegawa;Junhong Gao;H. Ishihara;A. Niijima;H. Mano;H. Aburatani;T. Asano;Y. Oka

Inter-organ communication via autonomic nerve circuits modulates systemic energy and glucose metabolism

通过自主神经回路的器官间通讯调节全身能量和葡萄糖代谢

• 发表时间: 2007
• 作者: Imai J.;Katagiri H.;Suzuki T.;Oka Y.;Katagiri H.
• 通讯作者: Katagiri H.