The role of nesfatin-1 in energy homeostasis

The crosstalk between adipocytes and the hypothalamus plays an impotent role in the regulation of food intake and energy homoeostasis. Largely unknown players in this crosstalk are so-called tanycytes. The cell bodies of these specialized ependymal glial cells contact the cerebrospinal fluid in the wall of the 3rd ventricle and send processes into the hypothalamic nuclei and the median eminence where they ensheath capillaries. Recent findings indicate that tanycytes are chemosensors responding with intracellular calcium waves to a number of stimuli such as glucose, ATP and histamine. Furthermore, tanycytes seem to be an important component of the hypothalamic stem cell population, which were associated with a regulation of the body weight. However, the detailed physiological functions of tanycytes are still unclear.

Based on the location as well as the function as chemosensors we postulate an important role of tanycytes in the regulation of food intake and energy homoeostasis. The focus of this research project is the clarification of a possible crosstalk of adipocytes and tanycytes via adipokines, such as leptin and nesfatin-1, as well as the impact of this crosstalk in metabolic regulation.

Topics for a PhD thesis are:

• Impact of peripheral nesfatin-1 in the adipocytic-tanycytic crosstalk and metabolic regulation
• Chemosensing of adipokines via tanycytes in the hypothalamic area

The doctoral researcher will generate AAV vectors for gene transfer in vivo. In addition to standard techniques of cell and molecular biology he/she will employ ex vivo techniques to study cellular effects of adipokines (e.g., [Ca2+]i measurements) and mouse models for the investigation of food intake and energy expenditure by using indirect calorimetry.

Publications

Müller-Fielitz, H., Stahr, M., Bernau, M., Richter, M., Abele, S., Krajka, V., Benzin, A., Wenzel, J., Kalies, K., Mittag, J., Heuer, H., Offermanns, S., and Schwaninger, M.: Tanycytes control the hormonal output of the hypothalamic-pituitary-thyroid axis. Nat Commun., vol. 8(1), , 2017, doi: 10.1038/s41467-017-00604-6