Novel non-invasive assessment of de novo lipogenesis and its mechanistic role in human insulin resistance

新的非侵入性评估从头脂肪生成及其在人胰岛素抵抗中的机制作用

• 批准号: MR/V011758/1
• 负责人: Alison Sleigh
• 金额: $ 68.2万
• 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: 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=MR%2FV011758%2F1
• 关键词: Novel; non; invasive; assessment; de

BackgroundWorldwide obesity has nearly tripled since 1975 and the World Health Organisation estimates 39% of the adult population are now overweight. Obesity can lead to diabetes and other metabolic disorders such as heart and fatty liver disease. This process can be gradual, quietly occurring over a number of years by a state of insulin resistance, where cells in muscle and liver don't respond well to the hormone insulin and blood sugars rise. Therefore it is imperative that we better understand the mechanisms of insulin resistance in order to be able to intervene at an earlier stage in the development of these diseases, where metabolic changes may still be reversible.Insulin resistance is closely associated with an accumulation of fat stored in the liver and skeletal muscle. There is growing evidence to suggest a process called de novo lipogenesis (DNL), where fat is generated from excess sugars, is involved in the development of insulin resistance. There are no non-invasive ways to measure the storage of fat from DNL, and taking a biopsy sample from the liver carries substantial risk. Therefore investigations into the storage of DNL-generated fats has been significantly limited. AimTo develop a non-invasive method to measure the storage of DNL-generated fats, and to use this to safely examine the relevance of this fat storage in human insulin resistance.ApproachMagnetic Resonance Spectroscopy (MRS) is a completely non-invasive technique that uses an MRI scanner to generate biochemical information from inside the body. This can tell us about the composition of the tissue and, for example, can measure how much fat it contains. However, normal methods can not distinguish DNL-generated fat from other fat, and so here I plan to design and validate a new special MRS method that will be able to do this. Using both insulin resistant patients and healthy individuals, we shall utilise this new method to investigate the role of DNL-stored fats in the mechanisms of insulin resistance. ImportanceNon-invasive methods to measure the storage of DNL-generated fats will safely enable the investigation of the relevance of stored DNL-fats in human insulin resistance. Understanding such mechanisms is key to preventing a number of metabolic diseases including diabetes, heart and fatty liver disease.

背景 自 1975 年以来，全球肥胖率几乎增加了两倍，世界卫生组织估计目前有 39% 的成年人超重。肥胖可导致糖尿病和其他代谢紊乱，例如心脏病和脂肪肝疾病。这个过程可以是渐进的，在胰岛素抵抗状态下悄然发生多年，在这种状态下，肌肉和肝脏中的细胞对胰岛素激素反应不佳，血糖升高。因此，我们必须更好地了解胰岛素抵抗的机制，以便能够在这些疾病发展的早期阶段进行干预，此时代谢变化可能仍然是可逆的。胰岛素抵抗与肝脏和骨骼肌中储存的脂肪积累密切相关。越来越多的证据表明，一种称为从头脂肪生成（DNL）的过程（脂肪是由过量的糖产生的）与胰岛素抵抗的发展有关。没有非侵入性的方法来测量 DNL 中脂肪的储存情况，并且从肝脏中获取活检样本存在很大的风险。因此，对 DNL 产生的脂肪储存的研究受到了极大的限制。目的开发一种非侵入性方法来测量 DNL 生成的脂肪的储存，并用它来安全地检查这种脂肪储存与人类胰岛素抵抗的相关性。方法磁共振波谱 (MRS) 是一种完全非侵入性的技术，使用 MRI 扫描仪从体内生成生化信息。这可以告诉我们组织的成分，例如，可以测量它含有多少脂肪。然而，普通方法无法区分 DNL 生成的脂肪和其他脂肪，因此我计划设计并验证一种新的特殊 MRS 方法，该方法将能够做到这一点。我们将利用胰岛素抵抗患者和健康个体，利用这种新方法来研究 DNL 储存的脂肪在胰岛素抵抗机制中的作用。重要性 通过非侵入性方法测量 DNL 生成的脂肪的储存量，将能够安全地研究储存的 DNL 脂肪与人类胰岛素抵抗的相关性。了解这些机制是预防许多代谢疾病（包括糖尿病、心脏病和脂肪肝疾病）的关键。

项目成果

Association of insulin resistance with the accumulation of saturated IMCL, compared with other fat stores.

与其他脂肪储存相比，胰岛素抵抗与饱和 IMCL 积累的关联。

• 发表时间: 2022
• 作者: Azhar MA