Targeting Adipose Senescence for Treatment of Diabetes
- Reference number
- ID19-0009
- Project leader
- Boucher, Jeremie
- Start and end dates
- 200101-241231
- Amount granted
- 2 500 000 SEK
- Administrative organization
- Göteborg University
- Research area
- Life Sciences
Summary
Cellular senescence (aging of cells) is a major factor behind deteriorated tissue function in the elderly. Impaired adipose tissue capacity to store lipids is closely associated with type 2 diabetes (T2D) and cardiovascular disease (CVD). Our preliminary results indicate that senescence of adipose tissue cells promotes local and systemic inflammation and insulin resistance by impairing adipogenesis and adipose tissue expansion. We propose to 1) characterize senescence markers in human adipose tissue in several large cross-sectional patient cohorts and investigate their relation to clinical phenotype. We will perform RNAseq from adipose tissue from individuals with a wide range in body mass index and adipose tissue morphology, with corresponding information on established T2D, family history of T2D and data on lipids, inflammation, insulin sensitivity, and CVD. 2) identify senescence-associated secreted factors from adipose tissue, and their associations with clinical phenotype. 3) determine the effect of the senescence-associated factors on preadipocyte, adipocyte and endothelial cell function, lipid transport and overall metabolism. Overall, we anticipate that this project will be able to identify the key drivers of adipose tissue senescence, and identify new adipose tissue senescence-associated factors which could be novel therapeutic targets for the treatment of cardiometabolic diseases.
Popular science description
Aging of cells or cellular senescence is a major factor behind tissue and organ function in the elderly. Impaired adipose tissue capacity to store lipids is closely associated with diabetes and cardiovascular diseases, at least in part due to fat accumulating in non-fat tissues causing detrimental effects. Our preliminary results indicate that cellular aging of adipose tissue cells plays a major role in this process, by secreting factors which promote inflammation and insulin resistance and impairing adipose tissue expansion. We propose to 1) characterize aging markers in human adipose tissue in several large human patient cohorts and investigate their relation to disease. We will perform gene expression analyses from adipose tissue from individuals with a wide range in body body weight and adipose tissue morphology, with corresponding information on established diabetes, family history of diabetes and data on lipids, inflammation, insulin sensitivity, and cardiovascular disease 2) identify senescence-associated secreted factors from adipose tissue, and their associations with diseases. We will measure secretion from adipose tissue of key factors identified, and their levels in blood from healthy non-obese, obese, and diabetic subjects, with or without cardiovascular complications 3) determine the effect of the senescence-associated factors on adipose tissue cell function, lipid transport and overall metabolism. Overall, we anticipate that this project will be able to identify the key drivers of adipose tissue aging, and identify factors which could be novel therapeutic targets for the treatment of cardiometabolic diseases.