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.

新陈代谢是在全身不同器官/组织之间协调和调节的。这种协调的代谢调节显然对维持系统稳态至关重要，特别是葡萄糖和能量代谢。因此，器官/组织之间的交流是极其重要的，这种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疾病发展的贡献者的多功能性已经确立。然而，最近的一些研究表明，组织特异性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，在传递器官间代谢信息方面起着重要作用。这可以通过发现传入肝迷走神经参与能量消耗和脂肪积累来证明。我们在肝脏中表达PPAR_γ，导致脂肪组织的脂肪分解增强，增加全身能量消耗。因此，作为对肝脏脂质积累的反应，肝迷走神经传入神经将有关过量能量积累的信息传递给大脑，从而增加交感神经的流出以增加能量消耗。我们的研究结果表明，大脑从周围器官/组织获得多种代谢信息，从而导致全身组织/器官之间的协同代谢调节。此外，在长期摄入过量卡路里的情况下，这些系统似乎有助于代谢综合征的病理特征。因此，阐明这些调节系统可能有助于揭示代谢稳态和代谢综合征发展的潜在机制。

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.