IMPC: Is Lrg1 an autocrine/paracrine regulator of thermogenesis in brown and beige adipose tissue? Implications for cardiometabolic disease.

IMPC：Lrg1 是棕色和米色脂肪组织中生热作用的自分泌/旁分泌调节剂吗？

• 批准号: MR/R014086/1
• 负责人: Lee Roberts
• 金额: $ 5.14万
• 依托单位: University of Leeds
• 依托单位国家: 英国
• 项目类别: Research Grant
• 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=MR%2FR014086%2F1
• 关键词: IMPC; Lrg1; autocrine; paracrine; regulator

Background: Our bodies store excess energy as fat inside special cells, called white fat cells (that form white adipose tissue). But not all fat cells are the same; brown fat cells (brown adipose tissue) break down stored fat to generate heat during exposure to cold, while beige fat cells can switch between the two, either storing or burning fat.It is thought that brown and beige fat cells have protective properties against obesity and type 2 diabetes, due to their fat burning activity. However, during aging and obesity the amount of brown and beige fat in our bodies decreases, while the amount of white fat increases. This may contribute to an increased risk of developing metabolic diseases such a type 2 diabetes. We do not yet fully understand why the amount of brown and beige fat decreases during obesity. Our experiments suggest that fat cells release a protein signal, known as Lrg1, which may enter the blood and decrease the fat burning ability of brown and beige fat cells. Lrg1 is increased in the blood of people with type 2 diabetes, and those who are obese. The concentration of Lrg1 in blood also increases with age. We don't yet know for certain whether Lrg1 decreases the fat burning ability of beige and brown fat in the body, or whether this contributes to accelerated development of type 2 diabetes. Research aims: This research in Dr Roberts' laboratory will determine whether "turning off" the gene for Lrg1 increases the amount of beige and brown fat cells, and their ability to burn fat. The research will also investigate whether switching off the Lrg1 gene protects against obesity and type 2 diabetes.Potential benefit to society and people with diabetes: Type 2 diabetes is a worldwide healthcare challenge; with an estimated 422 million people thought to have type 2 diabetes globally. In the UK the NHS spends £14 billion a year to treat diabetes. Understanding how obesity increases the risk of developing this disease, may lead to new treatments to target the twin global epidemics of obesity and type 2 diabetes. By studying the role Lrg1 plays in regulating the fat burning capacity of beige and brown fat cells, this research hopes to identify whether Lrg1 is a potential new therapy target to protect against the loss of beige and brown fat and the onset of obesity and type 2 diabetes.

背景：我们的身体将多余的能量以脂肪的形式储存在特殊的细胞中，称为白色脂肪细胞（形成白色脂肪组织）。但并非所有的脂肪细胞都是一样的;棕色脂肪细胞（棕色脂肪组织）在暴露于寒冷时分解储存的脂肪产生热量，而米色脂肪细胞可以在两者之间转换，要么储存脂肪，要么燃烧脂肪。棕色和米色脂肪细胞被认为具有预防肥胖和2型糖尿病的特性，因为它们的脂肪燃烧活性。然而，在衰老和肥胖的过程中，我们体内棕色和米色脂肪的数量减少，而白色脂肪的数量增加。这可能会增加患代谢性疾病的风险，如2型糖尿病。我们还不完全理解为什么棕色和米色脂肪的数量在肥胖期间减少。我们的实验表明，脂肪细胞释放一种蛋白质信号，称为Lrg 1，它可能进入血液，降低棕色和米色脂肪细胞的脂肪燃烧能力。lrg 1在2型糖尿病患者和肥胖者的血液中增加。血液中Lrg 1的浓度也随着年龄的增长而增加。我们还不确定Lrg 1是否会降低体内米色和棕色脂肪的燃烧能力，或者这是否会加速2型糖尿病的发展。研究目的：罗伯茨博士实验室的这项研究将确定“关闭”Lrg 1基因是否会增加米色和棕色脂肪细胞的数量，以及它们燃烧脂肪的能力。2型糖尿病是一种常见的糖尿病类型，其发病率高，发病率低，对糖尿病患者的健康危害大。2型糖尿病是一种常见的糖尿病类型，其发病率高，对糖尿病患者的危害大。在英国，NHS每年花费140亿英镑用于治疗糖尿病。了解肥胖如何增加患这种疾病的风险，可能会带来针对肥胖和2型糖尿病这两种全球流行病的新治疗方法。通过研究Lrg 1在调节米色和棕色脂肪细胞的脂肪燃烧能力中的作用，这项研究希望确定Lrg 1是否是一个潜在的新治疗靶点，以防止米色和棕色脂肪的损失以及肥胖和2型糖尿病的发病。

项目成果

Metabokines in the regulation of systemic energy metabolism

• DOI: 10.1016/j.coph.2022.102286
• 发表时间: 2022-09-19
• 期刊: CURRENT OPINION IN PHARMACOLOGY
• 影响因子: 4
• 作者: MacCannell, Amanda DV.;Roberts, Lee D.
• 通讯作者: Roberts, Lee D.

Sexual dimorphism in adipose tissue mitochondrial function and metabolic flexibility in obesity.

• DOI: 10.1038/s41366-021-00843-0
• 发表时间: 2021-08
• 期刊: International journal of obesity (2005)
• 作者: MacCannell ADV;Futers TS;Whitehead A;Moran A;Witte KK;Roberts LD
• 通讯作者: Roberts LD

Prospective Longitudinal Characterization of the Relationship between Diabetes and Cardiac Structural and Functional Changes.

糖尿病与心脏结构和功能变化之间关系的前瞻性纵向表征。

• DOI: 10.1155/2022/6401180
• 发表时间: 2022
• 期刊: Cardiology research and practice
• 影响因子: 2.1
• 作者: Chowdhary A;Jex N;Thirunavukarasu S;MacCannell A;Haywood N;Almutairi A;Athithan L;Jain M;Craven T;Das A;Sharrack N;Saunderson CED;Sengupta A;Roberts L;Swoboda P;Cubbon R;Witte K;Greenwood J;Plein S;Levelt E
• 通讯作者: Levelt E

Lrg1 is a Driver of Brown Adipose Tissue Dysfunction in Obesity

Lrg1 是肥胖症棕色脂肪组织功能障碍的驱动因素

• DOI: 10.1096/fasebj.2021.35.s1.00285
• 发表时间: 2021
• 期刊: The FASEB Journal
• 作者: MacCannell A

Temporal analysis of skeletal muscle remodeling post hindlimb ischemia reveals intricate autophagy regulation.

• DOI: 10.1152/ajpcell.00174.2022
• 发表时间: 2022-12-01
• 期刊: American journal of physiology. Cell physiology