Promotie: Molecular profiling and targeting of brain cells and circuits related to energy balance and food reward

Summary

Obesity and other eating disorders are major health issues that affect a large number of people. In 2019, half of adults in the Netherlands were overweight and 1 out of 7 were obese. In order to better understand obesity and develop treatments we need to more deeply investigate the brain cells and mechanisms underlying metabolic diseases. In this thesis, we aimed to better classify brain cells that are involved in food reward and energy balance and developed tools to better understand their function. First, we investigated cells in the hypothalamus of the brain that respond to leptin, a hormone that signals to increase energy expenditure and decrease food intake. By simultaneously measuring the activity of all genes, we showed that leptin-responsive cells are highly heterogeneous, which is reflected in their response to energy deficit. This information underlines the importance and diversity of leptin’s actions. Secondly, we developed genetic tools that allow us to investigate the function of brain cells. We defined criteria for specific parameters of dosing of these tools to more precisely target specific brain cells and developed a novel technique to alter the activity of brain cells and is used to dissect their role in diverse behavioral and pathological paradigms. Overall, the findings of this thesis build a basis to utilize knowledge of brain cells for the development of treatments for obesity and related metabolic diseases.