How to Ameliorate Metabolic Balance Using Rythmic GnRH in Eating disorderRS – HAMBURGERS

The overall objective of this proposal is to study the causal link between brain GnRH signaling and the regulation of food intake and energy metabolism, and to explore the therapeutic potential of pulsatile GnRH therapy for the treatment of eating disorders at the preclinical level. To this end, the HAMBURGERS project brings together leading experts in GnRH physiology and the control of energy homeostasis by the brain (Partner 1) along with a team with world-unique expertise in ultra-high field 17.4T magnetic resonance imaging, which enables the longitudinal follow-up of brain structure and function at high resolution in mice (Partner 2), and a team expert in engineering radiotracers and PET imaging to bring to scrutiny brain GnRH receptor bioavailability (Partner 3) with the following aims.
Aim 1. To strengthen the rationale for pulsatile GnRH treatment in eating disorders
Aim 2. To evaluate the impact of the absence of GnRH secretion and its restoration on structural and functional brain components in the mouse model
Aim 3. To determine whether GnRH neuronal dysfunction could lead to eating-disorder-related behaviors through its role in the activity of functional circuitry in the neuroendocrine-cognitive network
Aim 4. To develop and evaluate a new PET radiotracer to visualize brain GnRH receptors in vivo