Metabolism Regulated Epigenetics
Obesity is currently a worldwide epidemic affecting 11% of the global population that leads to associated pathologies such as diabetes, cardiovascular diseases, non-alcoholic fatty liver disease (NFALD) and some types of cancer. This is particularly alarming in Western societies, where obesity rates are about 20% and being overweight is in the area of 40-50%. These figures have dramatically increased over the last decades because of a shift from active to more sedentary modes of life and increased consumption of high caloric diets. Moreover, genetic factors also contribute to obesity.
Millions of years of mammalian evolution have shaped robust and intricate mechanisms of energy balance maintenance. Energy intake represents the daily intake of food, which is highly controlled by the central nervous system. On the other hand, the energy expenditure covers all the chemical reactions that consume energy necessary for basic vital functions or situations of increased energetic demand such as exercise. At the cellular level, these bioenergetic processes take place mainly in mitochondria.
Excess of energy is primarily stored as triglycerides in the white adipose tissue. However, brown adipose tissue (BAT) converts the chemical energy into heat due to uncoupling of oxidative phosphorylation, a phenomenon known as thermogenesis. The role of BAT for cold protection in neonates, small mammals and hibernating animals has been known for many years. However, BAT was thought to disappear throughout adult life in humans until a few years ago, when it has also been shown to be present and able to be activated in adults. Interestingly, the amount of BAT inversely correlates wit body mass index.
Understanding the molecular and cellular mechanisms of BAT activation might lead to the development of novel therapeutic strategies to shift the energy balance towards increased energy expenditure.
Over the past several years, I have uncovered a crucial role of the transcription factor Yin Yang 1 (YY1) in the control of metabolic pathways and energy balance in liver, skeletal muscle and adipose tissue. YY1 controls chromatin function by recruiting cofactors that affect histone modification.
Many chromatin factors use intermediary metabolites as cofactors or donors used for histone modifications. AcetylCoA, for example, a key metabolic intermediate is also a donor for histone acetylation. Therefore, the metabolic state of the cell could have a direct influence on chromatin function and the control of gene expression.
The main goal of our research is therefore to understand how an excess of dietary nutrients and energy-related environmental stimuli modulate the chromatin and epigenetic landscape, which in turn affects the physiological regulation of energy expenditure.
If you are interested in joining our group to study the role of epigenetic modifications in gene regulation, then please consider the following:
PhD students will be recruited through the Life Science Zurich Graduate School. Deadlines are twice a year (June/December). Please see the LSZGS website for further information: