Understanding the role of lipid remodelling in the modulation of human brown adipogenesis using a stem cell-based system

使用基于干细胞的系统了解脂质重塑在调节人类棕色脂肪生成中的作用

• 批准号: BB/X001237/1
• 负责人: Antonio Vidal-Puig
• 金额: $ 102.32万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FX001237%2F1
• 关键词: Understanding; role; lipid; remodelling; modulation

Brown adipose tissue is an essential organ for regulating body temperature and energy dissipation. Its function has been well characterised in mice and has recently attracted enormous interest in humans, where it shows some unique molecular and functional differences not well characterised. Individuals with substantial amounts of brown fat have a lower risk of diabetes, lower triglyceride levels and a healthier fat distribution. Conversely, obese insulin-resistant diabetic patients have few amounts and less active brown fat.Despite the potential relevance of brown adipose tissue to human health, the knowledge about human brown fat activation, development and maturation required for its exploitation is negligible. Initial evidence has revealed the importance of a specific type of lipids in maintaining an undifferentiated state in stem cells and the contribution of particular lipid species to the differentiation of specialised cell types. Obese patients exhibit altered lipid remodelling profiles in adipocytes, and we posit that these alterations may compromise successful brown adipose tissue maturation.There are two main difficulties to studying brown fat biogenesis in humans: a) insufficient knowledge about human-specific brown fat's molecular components and b) limited access to human brown fat because it is scarce and typically anatomically interspersed within the normal white fat.We have developed a unique protocol of brown fat adipocyte differentiation from human stem cells to overcome these two bottlenecks. Stem cells solve the problem of scalability, providing enough human brown fat to investigate. Also, because the protocol we have developed evolves through every stage of development, this novel approach enables for the first time the success in our objective of elucidating the dynamic role of lipids in human brown adipocytes differentiation and activation and provides a unique toolset to optimise its development by targeting its lipid metabolism.

棕色脂肪组织是调节体温和能量耗散的必不可少的器官。它的功能在小鼠中的特征很好，最近引起了人们对人类的巨大兴趣，在该小鼠中，它显示出某些独特的分子和功能差异未得到很好的特征。大量棕色脂肪的人患糖尿病风险较低，甘油三酸酯水平较低和脂肪分布更健康。相反，肥胖的胰岛素糖尿病患者的数量很少，棕色脂肪含量较低。尽管棕色脂肪组织与人类健康的潜在相关性，但对人类棕色脂肪激活，开发和剥削所需的成熟的了解却可以忽略不计。最初的证据揭示了特定类型的脂质在保持干细胞中未分化状态以及特定脂质物种对特殊细胞类型分化的贡献中的重要性。肥胖患者在脂肪细胞中表现出改变的脂质重塑谱，我们认为这些改变可能会损害成功的棕色脂肪组织成熟的成功。 Fat.我们已经开发了一种独特的棕色脂肪脂肪细胞分化与人类干细胞分化的方案，以克服这两个瓶颈。干细胞解决了可伸缩性问题，提供了足够的人类棕色脂肪进行研究。同样，由于我们制定的协议通过了开发的每个阶段而发展，因此这种新颖的方法首次可以成功地阐明脂质在人棕色脂肪细胞中的动态作用的成功，并提供了一种独特的工具集，并提供了一种通过其脂质代谢来靶向其发育的独特工具。

项目成果

Fuelling the fire: de novo lipogenesis primes thermogenesis

火上浇油：从头脂肪生成引发产热

• DOI: 10.1038/s42255-023-00865-0
• 发表时间: 2023
• 期刊: Nature Metabolism
• 影响因子: 20.8
• 作者: Rodríguez-Fdez S