ADIPOSE TISSUE DYSFUNCTION AND LIPOTOXICITY

脂肪组织功能障碍和脂毒性

• 批准号: MC_UU_00014/2
• 负责人: Antonio Vidal-Puig
• 金额: $ 365.95万
• 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%2F2
• 关键词: ADIPOSE; TISSUE; DYSFUNCTION; LIPOTOXICITY

Obesity is associated with insulin resistance, diabetes and cardiovascular problems. We want to know why and how obesity causes these problems and what can be done to either prevent or reverse it. For this purpose, we will investigate the molecular links between this cluster of pathologies. We think that one of the mechanisms that links obesity to other metabolic diseases is related to the impaired capacity of the adipose tissue (fat) to expand and function, causing it to release toxic lipid species that accumulate and affect other organs such as pancreas, liver and skeletal muscle.Specifically we aim to: a) understand the normal mechanisms enabling the adipose tissue to grow in a “healthy” way that does not result in the metabolic problems typically associated with obesity, such as diabetes and heart attacks; b) define whether targeting brown adipose tissue, a type of fat that uses fat to make heat, can prevent or reverse obesity and its associated diseases; and c) identify diagnostic biomarkers to identify the risk of developing complications as well as pathogenic therapeutically targetable mechanisms. For this purpose, we will use mouse models and cells, advanced experimental studies and technologies to validate our most significant findings before working with our collaborators to confirm them in humans.

肥胖与胰岛素抵抗、糖尿病和心血管问题有关。我们想知道肥胖为什么和如何导致这些问题，以及可以做些什么来预防或扭转它。为此，我们将研究这一组病理之间的分子联系。我们认为将肥胖与其他代谢性疾病联系在一起的机制之一与脂肪组织(脂肪)的扩张和功能受损有关，导致它释放有毒的脂类物质，积累并影响其他器官，如胰腺、肝脏和骨骼肌肉。具体而言，我们的目标是：a)了解使脂肪组织以“健康”的方式生长的正常机制，这种机制不会导致与肥胖相关的典型代谢问题，如糖尿病和心脏病发作；b)确定靶向棕色脂肪组织是否可以预防或逆转肥胖及其相关疾病；以及c)确定诊断生物标记物，以确定发生并发症的风险以及致病治疗的靶向机制。为此，我们将使用小鼠模型和细胞、先进的实验研究和技术来验证我们最重要的发现，然后与我们的合作者合作，在人类身上证实这些发现。

项目成果

CBL/CAP Is Essential for Mitochondria Respiration Complex I Assembly and Bioenergetics Efficiency in Muscle Cells.

• DOI: 10.3390/ijms24043399
• 发表时间: 2023-02-08
• 期刊: International journal of molecular sciences
• 影响因子: 5.6

Publisher Correction: Enhanced ß-adrenergic signalling underlies an age-dependent beneficial metabolic effect of PI3K p110a inactivation in adipose tissue.

出版商更正：增强的α-肾上腺素信号传导是脂肪组织中 PI3K p110a 失活的年龄依赖性有益代谢效应的基础。

• DOI: 10.1038/s41467-020-14939-0
• 发表时间: 2020
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Araiz C

Suppression of insulin-induced gene 1 (INSIG1) function promotes hepatic lipid remodelling and restrains NASH progression.

• DOI: 10.1016/j.molmet.2021.101210
• 发表时间: 2021-06
• 期刊: Molecular metabolism
• 影响因子: 8.1
• 作者: Azzu V;Vacca M;Kamzolas I;Hall Z;Leslie J;Carobbio S;Virtue S;Davies SE;Lukasik A;Dale M;Bohlooly-Y M;Acharjee A;Lindén D;Bidault G;Petsalaki E;Griffin JL;Oakley F;Allison MED;Vidal-Puig A
• 通讯作者: Vidal-Puig A