Brain control of food intake and body weight – Identification of targets for the treatment of obesity
Food intake is controlled by specific neurons located in the hypothalamus. The hypothalamic neuronal networks and the transmitters/
mediators regulating ingestive behavior and energy balance are poorly understood.
The research aims at investigating and clarifying the neuronal circuitries and hypothalamic mechanisms that control food intake. The expression of protein and transmitter mediators and microRNAs (miRNAs) is investigated in the hypothalamus of normal animals and mouse models of genetic obesity by immunohistochemistry (confocal microscopy), Western blotting, in situ hybridization and RT-PCR. Using laser microdissection microscopy and microarray technology, we try to find novel genes in selected hypothalamic neuronal populations that participate in the regulation of food intake. Since some hypothalamic neuronal populations are under the influence of circulating hormones, such as leptin and ghrelin, special interest is focussed on molecular components of the blood-brain barrier (BBB) in relation to neurons that control energy balance.
Obesity is a major contributing risk factor to leading causes of death, including cardiovascular disease, diabetes and certain cancers. The present research project will provide new important information on how the hypothalamus regulates food intake and weight homeostasis. The information gained from this project may be used to develop pharmaceutical approaches for the treatment of the increasing population of obese individuals.
Section of the mouse brain stained with cresyl violet (left) illustrating the hypothalamus (in rectangle).
Image to the right shows the hypothalamus after locked nucleic acid-based in situ hybridization to detect cells expressing microRNA-7a (miR-7a).
Arc = arcuate nucleus; DMH = dorsomedial hypothalamic nucleus; ME = median eminence; VMH = ventromedial hypothalamic nucleus; 3V = third ventricle.
MicroRNAs in the hypothalamus.
Neuroendocrinology 2013 ;98(4):243-53
Delta-like 1 homologue is a hypothalamus-enriched protein that is present in orexin-containing neurones of the lateral hypothalamic area.
J. Neuroendocrinol. 2013 Jul;25(7):617-25
Locked nucleic acid-based in situ hybridisation reveals miR-7a as a hypothalamus-enriched microRNA with a distinct expression pattern.
J. Neuroendocrinol. 2012 Dec;24(12):1492-504
P2X2 purinoreceptor protein in hypothalamic neurons associated with the regulation of food intake.
Neuroscience 2010 Nov;171(1):62-78
Neurotransmitters in key neurons of the hypothalamus that regulate feeding behavior and body weight.
Physiol. Behav. 2007 Sep;92(1-2):263-71