Skeletal muscle and adipose cross talk identifying novel mediators of insulin sensitivity
Lead Research Organisation:
University of Birmingham
Department Name: Institute of Inflammation and Ageing
Abstract
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
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
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/N504002/1 | 01/11/2015 | 31/10/2019 | |||
| 1733068 | Studentship | BB/N504002/1 | 02/11/2015 | 01/11/2019 | Thomas Nicholson |
| Description | We have characterised, for the first time in humans, a new substance produce by fat cells, that can improve how muscles handle sugar which may in the future may lead to improved treatments to manage blood sugar levels in conditions such as type II diabetes. We have also grown cells from human muscle samples in the lab and identified that muscle from obese people is different to muscle from lean people and doesn't seem to function as well. Therefore these differences may be able to be targeted to improve the muscle from obese people. We have also started to investigate and characteristic small packages that cells secrete, called vesicles, our data may show that this is a way fat cells communicate with other cells, such as muscle cells and this may be a mechanism that becomes altered with obesity |
| Exploitation Route | Future studies may be able to take forward the findings from this study to lead to new therapeutics aimed to help manage blood sugar levels in conditions such as type II diabetes. The differentially expressed and secreted proteins by fat cells may also be studied in other disease areas that are known to function through similar intracellular signalling pathways. |
| Sectors | Healthcare,Pharmaceuticals and Medical Biotechnology |