Mechanisms in Disorders of Energy Balance

能量平衡紊乱的机制

• 批准号: MC_UU_00014/1
• 负责人: Giles Yeo
• 金额: $ 381.7万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Intramural
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MC_UU_00014%2F1
• 关键词: Mechanisms; Disorders; Energy; Balance

We aim to understand the biological processes controlling what we eat and how we store and use energy. These pathways are disturbed in obesity and related metabolic conditions such as Type 2 diabetes. This knowledge will, ultimately, lead to development of new treatments for these disorders.We know that an individual’s genetic make-up has a significant role in determining susceptibility to developing obesity and its deleterious consequences. Recent advances have made it substantially easier to analyse human genetic code. We aim to exploit data from human genetic studies to gain fundamental insights into what causes human obesity, and propose to combine these genetic studies with laboratory studies based around cell lines and whole animal models to better understand the pathways involved.This programme builds on our previous work centred around a large group of patients from around the world who developed severe obesity as children and formed the basis for subsequent detailed studies on food intake and energy use. While humans will always be our experimental subject of choice, there are important mechanistic questions that require alternative approaches. We will use rodent models to explore aspects of disease processes that cannot be readily addressed in humans. Further, rodents have the advantage of being readily susceptible to genetic manipulation allowing precise alteration of specific genes and, importantly, creation of animal models of relevant, specific, human diseases.

我们的目标是了解控制我们吃什么以及我们如何储存和使用能量的生物过程。这些途径在肥胖症和相关代谢疾病如2型糖尿病中受到干扰。这些知识最终将导致这些疾病的新治疗方法的发展。我们知道，一个人的基因组成在决定肥胖的易感性及其有害后果方面起着重要作用。最近的进展使分析人类遗传密码变得容易得多。我们的目标是利用人类基因研究的数据，从根本上了解导致人类肥胖的原因，并建议将联合收割机这些遗传学研究与基于细胞系和整个动物模型的实验室研究相结合，以更好地了解所涉及的途径。这项计划建立在我们以前的工作基础上，这些工作围绕着来自世界各地的一大批儿童严重肥胖的患者，并为随后的研究奠定了基础。对食物摄入和能量使用的详细研究。虽然人类将永远是我们选择的实验对象，但仍有一些重要的机械问题需要替代方法。我们将使用啮齿动物模型来探索人类无法轻易解决的疾病过程的各个方面。此外，啮齿类动物具有容易受到遗传操作的影响的优点，从而允许精确改变特定基因，并且重要的是，创建相关的、特定的人类疾病的动物模型。

项目成果

A program of successive gene expression in mouse one-cell embryos

• DOI: 10.1016/j.celrep.2023.112023
• 发表时间: 2023-01-31
• 期刊: CELL REPORTS
• 影响因子: 8.8
• 作者: Asami, Maki;Lam, Brian Y. H.;Perry, Anthony C. F.
• 通讯作者: Perry, Anthony C. F.

The vagus nerve mediates the physiological but not pharmacological effects of PYY3-36 on food intake.

迷走神经介导 PYY3-36 对食物摄入的生理作用，但不介导药理作用。

• DOI: 10.1016/j.molmet.2024.101895
• 发表时间: 2024
• 期刊: Molecular metabolism
• 影响因子: 8.1
• 作者: Alonso AM

Human embryonic genome activation initiates at the one-cell stage.

• DOI: 10.1016/j.stem.2021.11.012
• 发表时间: 2022-02-03
• 期刊: Cell stem cell
• 影响因子: 23.9
• 作者: Asami M;Lam BYH;Ma MK;Rainbow K;Braun S;VerMilyea MD;Yeo GSH;Perry ACF
• 通讯作者: Perry ACF

A multi-component screen for feeding behaviour and nutritional status in Drosophila to interrogate mammalian appetite-related genes

• DOI: 10.1101/2020.05.04.076489
• 发表时间: 2020-05
• 期刊: bioRxiv
• 作者: J. Chalmers;Y. Tung;C. Liu;C. O'Kane;S. O’Rahilly;G. Yeo