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Marco Koch | Principle Investigator
Foto: AKR Anna Rowedder


NEUROBIOLOGY OF METABOLISM

Marco Koch


The hypothalamus is a part of the forebrain that is predominately supervising elementary vegetative body functions, such as reproduction, water and food intake. In this, the hypothalamic arcuate nucleus represents the master feeding centre, being responsible for control of homeostatic feeding behaviour and regulation of energy metabolism. The arcuate nucleus harbours specific groups of neurons: the orexigenic AgRP/NPY neurons, which when activated promote hunger and decrease energy expenditure, and the anorexigenic POMC neurons that are driving gradual onset of satiety and increase energy expenditure. The activity of these two functionally opposing groups of neurons is reciprocally controlled by diverse humoral factors derived from the blood stream (e.g. leptin or ghrelin) and by local synaptic input organization, the latter presumably involving local glial cells, such as tanyctes, astrocytes and microglia. With regard to patients suffering from overeating or anorexia, better mechanistic insights into the respective neural hypothalamic network that is controlling feeding and energy expenditure is of substantial clinical relevance today. Thus, we want to understand the mechanisms behind central regulation of feeding behaviour and energy metabolism.


Data

PD Dr. phil. nat Marco Koch

Email : marco.koch@medizin.uni-leipzig.de

Phone : +49 341 9722047

Address : Institute of Anatomy | Eilenburger Str. 13-15 | D-04317 Leipzig


Project_1

Dissect the precise mechanisms behind endocannabinoid signalling in hypothalamic feeding centres.

funded by DFG-SFB 1052/A07

Endocannabinoids are lipid messengers within the brain that generally transmit the same biological effects via cannabinoid receptor type 1 (CB1) when compared to well-known exogenous cannabinoids, such as THC. Moreover, endocannabinoids are able to induce physiological and pathological effects independently from CB1 activation. Cannabinoids were generally addressed as important metabolic messengers within the body, however the precise mechanisms behind endocannabinoid signalling in central hypothalamic feeding centers is not well investigated. Thus, our research will focus on novel mechanistic insights on how endocannabinoids in the hypothalamic arcuate nucleus will contribute to orchestration of whole-body energy homeostasis. In this context, preliminary work to our project demonstrated that endocannabinoids are present in the arcuate nucleus and thus might affect POMC and AgRP/NPY neurons (see Figure 1).

Figure 1: Enzymes of endocannabinoid biosynthesis (upper panel, red: NAPE-PLD; lower panel, red: DAGL) are present in POMC neurons (green). Bar = 25 μm.

Beatrice Schützelt MSc, PhD Student


Project_2

Investigate the role of microglia in physiological control of feeding behaviour

Funded by DFG KO 4267/2-1

POMC neurons drive gradual onset of satiety and increase in energy expenditure. Impaired POMC neuronal function in the cause of diet-induced obesity is associated with increase in local hypothalamic inflammatory markers and reactive microglia found in the hypothalamic arcuate nucleus of obese individuals. As resident macrophages, microglia predominantly function as an integral part of the immune defence in the brain. However, microglia were also addressed to actively contribute to synaptic pruning during brain development and in the cause of synaptic plasticity. Since local synaptic input organization is a fundamental prerequisite for AgRP/NPY and POMC neurons in order to adequately adapt their activity upon physiological metabolic shifts, e.g. from caloric restriction to chronic overeating, we want to investigate the active role of local microglia in synaptic input organization of the neural network in the arcuate nucleus responsible for physiological maintenance of whole-body energy metabolism.

Figure 2:


Project_3

Analyse the metabolic function of local dopaminergic neurons in the hypothalamic arcuate nucleus in maintenance of energy homeostasis

Local dopaminergic neurons in the arcuate nucleus were recently identified as orexigenic neurons that directly contribute to maintenance of energy homeostasis. In this, it was described that the gut derived orexigenic hormone ghrelin excites dopaminergic neurons in the arcuate nucleus in order to evoke an acute feeding response. We aim to analyse whether other metabolic relevant humoral factors (e.g. leptin) or local hypothalamic messengers (e.g. endocannabinoids) may contribute to control of local dopaminergic neurons in the arcuate nucleus for maintenance of energy homeostasis.

Figure 3: The hypothalamic arcuate nucleus contains AgRP/NPY neurons (blue), dopamine neurons (red) and POMC (green) neurons.

Laura Dietrich MD Student