Cell Models

Type 2 diabetes is a complex disease and obesity and physical inactivity represent strong risk factors for disease progression. Several tissues are deregulated and become dysfunctional including the main units for energy disposal and storage: skeletal muscle and fat tissue. Balancing the level of muscle usage with the amounts of lipids stored in the fat cells is crucial for metabolic homeostasis and is regulated at several levels.

We isolate muscle stem cells (satellite cells) from human skeletal muscle and grow and differentiate them in culture. This allows us to investigate if this early myocyte stage is affected by lifestyle-related factors such as physical inactivity, obesity and type 2 diabetes.

In addition to myocytes, we also isolate and study adipocytes from humans, in particular brown adipocytes. Recently, brown adipocytes were identified in adult humans. We find brown adipose tissue particularly interesting, because in addition to storing energy as “normal” white fat, it is also able to consume fat by producing heat as a physiological response to cold. Several studies have demonstrated that a brown fat-like-phenotype can be induced in white fat in mice e.g. in response to exercise, a process called “browning”. Although exercise to date has not proven to induce a brown fat phenotype in white fat of humans, certain disease conditions imply that browning of white fat could also occur in humans. We are currently addressing this question from different angles, previously not investigated. Our over-all hypothesis is that induction of brown fat depots as well as browning of white fat depots in obese humans will counteract obesity and type 2 diabetes.

We utilize a translational approach to study the mechanism of brown fat activation and induction of browning in white fat. By isolating stem cells from brown and white fat biopsies derived from people with a broad metabolic profile or from human subjects exposed to cold, we hope to identify specific regulators of brown fat and browning.

Non-coding RNAs are increasingly recognized as important regulators of cell identity and function. These molecules are not coding for any proteins but represent functional units that control gene expression and protein function at several levels in the cell. We have developed various methods to study the role of non-coding RNAs in brown fat activation and white fat browning. We perform these studies in isolated fat precursor cells that we are able to study during in vitro differentiation into mature fat.