Our current project aims at elucidating the hypothalamic neuronal circuitries and chemical mediators that participate in regulation of food intake and body weight. Food intake is controlled by specific neurons located in the hypothalamus. The hypothalamic neuronal networks and the transmitters/mediators regulating ingestive behaviour are poorly understood. A series of experiments have been designed, which aim at determining the neuronal circuitries, hypothalamic mediators and signal transduction mechanisms by which peripheral hormones such as leptin and ghrelin control food intake and energy expenditure. Novel proteins and transmitter mediators in the hypothalamus that are involved in regulation of body weight will be investigated in murine models of genetic obesity, including the ob/ob (= leptin-deficient), db/db (long leptin receptor-deficient; Ob-Rb), agouti (A/A) or tubby tub/tub (= tubby protein-deficient) mouse. The expression and regulation of protein mediators and receptors will be studied using immunohistochemistry (confocal microscopy), Western blotting, RT-PCR and in situ hybridization. The effect of proteins and transmitters will be investigated in vivo using an a food intake monitoring system.
The project combines the unique competence of two laboratories and is highly multidisciplinary. It will give the student opportunities to learn state-of-the-art methods for the study of protein localization, gene expression/regulation, and ingestive behaviour in genetic animal models of obesity. Obesity is a major contributing risk factor to leading causes of death, including cardiovascular disease, diabetes and certain cancers. The brain's critical role in regulating energy and fat balance has in the context of body weight regulation never been more apparent. The present research project is timely right and 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 new pharmaceutical approaches for the treatment of the increasing population of obese individuals.