Exploring the adipose tissue
The adipose tissue is a central tissue in the regulation of energy and glucose homeostasis. It acts as an energy depot but also as an endocrine organ, sending signals to the brain to inform about the energy status of the body. It responds to insulin and therefore is fundamental in regulating glucose levels. A dysfunctional adipose tissue leads to metabolic impairment. We focus on molecular mechanisms of adipose tissue dysfunction and drugs that affect adipose tissue metabolic capability.
Project description
We employ the groundbreaking CRISPR-Cas9 technology in human adipocytes to functionally characterize genes implicated in development of metabolic diseases, with focus on type 2 diabetes and obesity. We aim to elucidate disease mechanisms and identify potential drug targets for disease treatment. By gene-editing human preadipocytes and differentiating them into mature adipocytes in vitro, we can functionally assess the impact of genes of interest on relevant metabolic and molecular measures, such as glucose uptake, insulin signalling, adipogenesis, lipolysis and gene and protein expression.
We use an advanced automated imaging system which allows us for quick and unbiased image analysis of large experimental set-ups for assesments such as adipogenesis, protein expression and gene-editing efficiency. We work with both human primary cells, obtained from our clinic, and cell lines. Also, we explore pharmacological effects of drug known to induce insulin resistance, such as glucocorticoids, on fat cells metabolism. Together with transcriptomics analysis, we can find new target genes for our CRISPR pipeline.
Chosen publications
Kamble PG, Hetty S, Vranic M, Almby K, Castillejo-López C, Abalo XM, Pereira MJ, & Eriksson JW. Proof-of-concept for CRISPR/Cas9 gene editing in human preadipocytes: Deletion of FKBP5 and PPARG and effects on adipocyte differentiation and metabolism. Scientific Reports 2020 10 10565.
Pereira MJ, Vranic M, Kamble PG, Jernow H, Kristófi R, Holbikova E, Skrtic S, Kullberg J, Svensson MK, Hetty S, & Eriksson JW. CDKN2C expression in adipose tissue is reduced in type 2 diabetes and central obesity: impact on adipocyte differentiation and lipid storage? Translational Research 2021.