Balázs Juhász 1, Dániel Kuti 2, Zsuzsanna Winkler 2, Krisztina Kovács 1
1,2 Laboratory of Molecular Neuroendocrinology, Institute of Experimental Medicine,Hungarian Academy of Sciences, Budapest
The hypothalamus plays a major role in feeding behaviour and energy homeostasis. Several regions of the hypothalamus such as the nucleus arcuate, ventromedial nucleus and paraventricular nucleus get involved in this regulation to integrate peripheral and paracrine signals to modulate food intake and energy expenditure.
Our purpose was to observe the energy homeostasis regulation during short-term fasting. How can the food deprivation affect the neuroinflammation in the hypothalamus at the gene expression level and investigate how can the microglia and ketone bodies influence these changes?
The C57Bl6 mice were exposed to overnight (18h) starvation. Mice were group housed and maintained under controlled conditions with food and water available ad libitum unless otherwise stated. Plasma corticosterone was measured by direct RIA. Moreover, the gene expression changes were investigated in the hypothalamus by quantitative real-time PCR.
The Agrp and the NPY neurons of the arcuate nucleus showed a significantly elevated gene expression in the starved animals. Otherwise, the POMC gene expression was significantly reduced. Furthermore, the CRH mRNA level was significantly increased, but it did not elevate significant the plasma CORT level in the starved animals. The gene expression changes of the proinflammatory cytokines did not show any changes. Even though the IκB gene expression level was increased.
First, we could investigate a high mRNA level of the Agrp and NPY, which implies that the regulation of the food intake was increased and the energy expenditure was reduced. On the other hand, these orexin neurons and the paraventricular CRH neurons blocked the unorexin pathway that’s why the POMC gene expression level was reduced. The elevated IκB level which inhibits NF-κB implies that the main proinflammatory TF perhaps could not regulate the proinflammatory cytokines gene transcription which can be seen at the mRNA level of these genes.
Doctoral School: Neurosciences of János Szentágothai, University of Semmelweis
Supervisor: Dr. Krisztina Kovács
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