Energyhomeostatic neurons of the mouse hypothalamus

The ability to take up and metabolize nutrients is vitally important for the survival of every living organism. Higher organisms need to control their energy uptake and expenditure, as a positive energy balance over time can lead to obesity and even early death. The regulation of energy homeostasis, according to the neurocentric model, is performed by a small neuronal subnetwork in the hypothalamus. This network comprises, among others, satiety mediating, pro-opiomelanocortin (POMC) expressing neurons and hunger mediating, agouti-related protein (AgRP) expressing neurons. They integrate signals from the periphery about the nutritional status of the organism and relay this information onto second order neurons (e.g. SIM1 neurons in the paraventricular nucleus of the hypothalamus). Diet-induced obese mice that have received a high-fat diet can be used to investigate the effects of a prolonged positive energy balance on this network. In this thesis, the effects of a high-fat diet on the calcium homeostasis of POMC neurons were investigated. In addition, candidates for putative second order neurons to POMC neurons (SIM1 neurons) and their cellular properties were characterized.

Autorentext

Moritz Paehler was born in 1980 in Bonn, growing up inMeckenheim. He finished school in 2000 and moved on to studybiology in Cologne 2000 - 2009. He enjoys reading, writing,running and surfing.

Klappentext

The ability to take up and metabolize nutrients isvitally important for the survival of every livingorganism. Higher organisms need to control theirenergy uptake and expenditure, as a positive energybalance over time can lead to obesity and even earlydeath. The regulation of energy homeostasis,according to the neurocentric model, is performed bya small neuronal subnetwork in the hypothalamus. Thisnetwork comprises, among others, satiety mediating,pro-opiomelanocortin (POMC) expressing neurons andhunger mediating, agouti-related protein (AgRP)expressing neurons. They integrate signals from theperiphery about the nutritional status of theorganism and relay this information onto second orderneurons (e.g. SIM1 neurons in the paraventricularnucleus of the hypothalamus). Diet-induced obese micethat have received a high-fat diet can be used toinvestigate the effects of a prolonged positiveenergy balance on this network. In this thesis, theeffects of a high-fat diet on the calcium homeostasisof POMC neurons were investigated. In addition,candidates for putative second order neurons to POMCneurons (SIM1 neurons) and their cellular propertieswere characterized.