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Skeletal muscle and adipose cross talk identifying novel mediators of insulin sensitivity

骨骼肌和脂肪串扰识别胰岛素敏感性的新介质

基本信息

批准号：
1733068
负责人：
金额：
--
依托单位：
University of Birmingham
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2015
资助国家：
英国
起止时间：
2015 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=studentship-1733068
关键词：
Skeletal muscle adipose cross talk

项目摘要

The role of candidate adipose/muscle cross-talk mediators in mediating cellular metabolism and insulin signalling activity in human tissues is not well established. In order to identify the key cross-talk mediators and to validate their role in regulating cellular metabolism and insulin signalling pathways it is critical to initially conduct such studies using human derived primary cells, and then to back-translate these findings into appropriate in vivo models. The objective of this studentship is to investigate the role of muscle/adipose cellular cross talk and its effect of skeletal muscle metabolic phenotype and insulin signalling so that new targets which mediate insulin sensitivity and cellular metabolism can be identified and validated in preclinical models. Mechanistic adipose and muscle cellular cross-talk studies have predominantly been performed using murine cells (e.g C2C12 cell line), which are not suitable for target identification studies due to their different metabolic phenotype. Importantly, for this study we have a substantial and growing collection of human muscle and patient-matched adipose samples from both lean and obese individuals. Furthermore, in vitro cellular cross-talk studies will be conducted using primary human myotubes and patient-matched adipocytes. We will then back-translate these findings into appropriate animal models in order to perform in vivo target validation studies. The objectives of this project are therefore as follows. 1. To identify novel adipose/muscle cross-talk mediators through lipidomic and proteomic mass-spectroscopy analysis of human adipose tissue from both normal weight and obese individuals 2. Establish bespoke ex vivo models of human adipose/muscle cross-talk 3. Validate using appropriate models novel mediators of adipose/muscle cross-talk in regulating cellular metabolic phenotype and insulin sensitivity

候选脂肪/肌肉串扰介质在人体组织中介导细胞代谢和胰岛素信号活动中的作用尚未很好地确定。为了确定关键的串扰介质并验证其在调节细胞代谢和胰岛素信号通路中的作用，关键是首先使用人源性原代细胞进行此类研究，然后将这些发现反向转化为适当的体内模型。本研究的目的是研究肌肉/脂肪细胞串扰的作用及其对骨骼肌代谢表型和胰岛素信号传导的影响，以便在临床前模型中识别和验证介导胰岛素敏感性和细胞代谢的新靶点。机械脂肪和肌肉细胞串扰研究主要使用小鼠细胞（例如C2C12细胞系）进行，由于其不同的代谢表型，不适合用于靶标鉴定研究。重要的是，在这项研究中，我们收集了大量和不断增长的人体肌肉和患者匹配的脂肪样本，这些样本来自瘦肉和肥胖个体。此外，体外细胞串扰研究将使用原代人肌管和患者匹配的脂肪细胞进行。然后，我们将把这些发现转化为适当的动物模型，以便进行体内靶标验证研究。因此，本项目的目标如下。1. 通过对正常体重和肥胖人群脂肪组织的脂质组学和蛋白质组学质谱分析，鉴定新的脂肪/肌肉串扰介质2。建立人体脂肪/肌肉串扰的定制离体模型使用适当的模型验证脂肪/肌肉串扰调节细胞代谢表型和胰岛素敏感性的新介质

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

IL-6 secretion in osteoarthritis patients is mediated by chondrocyte-synovial fibroblast cross-talk and is enhanced by obesity.

DOI：
10.1038/s41598-017-03759-w
发表时间：
2017-06-14
期刊：
Scientific reports
影响因子：
4.6
作者：
Pearson MJ;Herndler-Brandstetter D;Tariq MA;Nicholson TA;Philp AM;Smith HL;Davis ET;Jones SW;Lord JM
通讯作者：
Lord JM

The role of adipokines in skeletal muscle inflammation and insulin sensitivity.