Adipose CaMKI: a pivotal controller of triglyceride metabolism

脂肪 CaMKI：甘油三酯代谢的关键控制器

• 批准号: BB/W001004/1
• 负责人: Marc Dionne
• 金额: $ 92.96万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FW001004%2F1
• 关键词: Adipose; CaMKI; pivotal; controller; triglyceride

Obesity is a significant, and growing, public health issue in the United Kingdom. Though overweight itself is often not unhealthy, obesity can predispose people to develop other, more serious, health problems. One of the most common diseases caused by obesity is type-2 diabetes, in which the body no longer responds properly to insulin. Many aspects of obesity itself, and the diseases it can cause, are not well understood: we don't fully understand how other parts of the body communicate with adipose (fat) cells, and we don't fully understand how adipose cells communicate with one another, to regulate the amount of fat they contain; we don't fully understand how the communications between these cells actually causes changes in fat accumulation. The answers to these cellular questions would help us understand why some people become obese and others don't, and why some obese people develop diabetes and others don't.We will study these issues in fruit flies. Many of the mechanisms of metabolic regulation are similar between flies and people, but flies are relatively easy and inexpensive to work with. We have unexpectedly found that a gene called CaMKI is required for normal fat metabolism in flies. Flies that don't have CaMKI are extremely obese--they have about four times as much fat as normal flies--but they are also healthy: they live as long as normal flies and apparently are not diabetic. This suggests that CaMKI is important in controlling fat accumulation and also in the development of diabetes.CaMKI is a kind of protein called a kinase. Kinases function by modifying other proteins; kinase activity is often responsive to signals from outside the cell. Our experiments will test how CaMKI is involved in the adipose cells' ability to receive signals from other tissues, whether CaMKI is involved in the development of diabetes, and how CaMKI actually works to change the accumulation of fat--what proteins are modified by CaMKI and what the effects are of that modification.Our preliminary results, combined with the experiments we propose, represent a dramatic step in our knowledge of how adipose cells control their fat level and how fat accumulation can lead to diabetes. Our work will have significant implications regarding metabolic regulation and metabolic disease and may help us understand the nature of "healthy" obesity.

肥胖是英国一个重要且日益严重的公共卫生问题。虽然超重本身通常不是不健康的，但肥胖会使人们容易患上其他更严重的健康问题。肥胖引起的最常见的疾病之一是2型糖尿病，在这种情况下，身体不再对胰岛素做出适当的反应。肥胖本身的许多方面，以及它可能导致的疾病，都没有得到很好的理解：我们不完全了解身体的其他部位如何与脂肪细胞沟通，我们不完全了解脂肪细胞如何相互沟通，以调节它们所含的脂肪量;我们不完全了解这些细胞之间的沟通实际上是如何引起脂肪积累的变化的。这些细胞问题的答案将帮助我们理解为什么有些人会变得肥胖而有些人不会，为什么有些肥胖的人会患糖尿病而有些人不会。苍蝇和人类之间的许多代谢调节机制是相似的，但苍蝇相对容易和便宜。我们意外地发现，一种名为CaMKI的基因是果蝇正常脂肪代谢所必需的。没有CaMKI的苍蝇非常肥胖--它们的脂肪是正常苍蝇的四倍--但它们也很健康：它们和正常苍蝇一样长寿，而且显然没有糖尿病。这表明CaMKI在控制脂肪积累和糖尿病的发展中很重要。CaMKI是一种称为激酶的蛋白质。激酶通过修饰其他蛋白质发挥作用;激酶活性通常对来自细胞外的信号做出反应。我们的实验将测试CaMKI是如何参与脂肪细胞从其他组织接收信号的能力，CaMKI是否参与糖尿病的发展，以及CaMKI实际上是如何改变脂肪的积累的-CaMKI修饰了哪些蛋白质以及这种修饰的效果是什么。我们的初步结果，结合我们提出的实验，代表了我们对脂肪细胞如何控制其脂肪水平以及脂肪积累如何导致糖尿病的知识的一个戏剧性的进步。我们的工作将对代谢调节和代谢疾病产生重要影响，并可能帮助我们了解“健康”肥胖的本质。

项目成果

TECPR1 conjugates LC3 to damaged endomembranes upon detection of sphingomyelin exposure.

• DOI: 10.15252/embj.2022113012
• 发表时间: 2023-09-04
• 期刊: EMBO JOURNAL
• 影响因子: 11.4
• 作者: Boyle, Keith B.;Ellison, Cara J.;Elliott, Paul R.;Schuschnig, Martina;Grimes, Krista;Dionne, Marc S.;Sasakawa, Chihiro;Munro, Sean;Martens, Sascha;Randow, Felix
• 通讯作者: Randow, Felix

Pre-copulatory reproductive behaviours are preserved in Drosophila melanogaster infected with bacteria.

• DOI: 10.1098/rspb.2022.0492
• 发表时间: 2022-05-11
• 期刊: PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
• 影响因子: 4.7
• 作者: Rose, Saloni;Beckwith, Esteban J.;Burmester, Charlotte;May, Robin C.;Dionne, Marc S.;Rezaval, Carolina
• 通讯作者: Rezaval, Carolina

High sugar diets can increase susceptibility to bacterial infection in Drosophila melanogaster

高糖饮食会增加果蝇细菌感染的易感性

• DOI: 10.1101/2023.12.07.570705
• 发表时间: 2023
• 作者: Darby A

Bacterial Toxin-Triggered Release of Antibiotics from Capsosomes Protects a Fly Model from Lethal Methicillin-Resistant Staphylococcus aureus (MRSA) Infection.

• DOI: 10.1002/adhm.202200036
• 发表时间: 2022-07
• 期刊: Advanced healthcare materials
• 影响因子: 10
• 作者: Tonkin RL;Klöckner A;Najer A;Simoes da Silva CJ;Echalier C;Dionne MS;Edwards AM;Stevens MM
• 通讯作者: Stevens MM

A serine-folate metabolic unit controls resistance and tolerance of infection

丝氨酸-叶酸代谢单位控制感染的抵抗力和耐受性

• DOI: 10.1101/2022.11.25.517956
• 发表时间: 2022
• 作者: Grimes K