Obesity represents one of the main health challenges of the 21st century. Its high incidence and adverse impact on health poses a heavy socioeconomic burden in most European countries. Current treatment modalities are limited and bariatric surgery is often the only option. Energy homeostasis is a complex process that critically depends on the regulated communication between the gastrointestinal tract and the brain. Specific signals inform the brain about nutrient stores as well as the ingestive status, thereby influencing meal initiation and termination. In this context, scientists on the EU- funded 'European obesity consortium studying the hypothalamus and its interaction with peripheral organs' (EUROCHIP) project proposed that devising new treatments for obesity requires in-depth investigation of the signals from the gut to the brain. Researchers performed extensive gene expression analysis to identify the effector systems in the hypothalamus and brainstem, which are regulated by gut peptides such as ghrelin. They discovered that chronic ghrelin administration increased food intake and that a high fat diet rendered certain parts of the brain resistant to the activity of ghrelin. Also they found that ghrelin regulated metabolic homeostasis through the activation of genes involved in the oxidative phosphorylation pathway. Leptin, the satiety hormone and insulin signalling in neurons were critical for regulating blood glucose levels and body weight. Simultaneous blocking of these two parameters was proposed as a potential strategy for altering blood glucose levels. Team members studied obese families and discovered gene variants associated with appetitive behaviour. Four new obesity susceptibility loci were identified while the majority of mutations were associated with loss of function of nerve growth factor-mediated signalling. Project outcomes have revealed critical factors affecting food intake and body weight control. These could be used to develop novel obesity interventions to treat even childhood obesity.
Obesity, energy homeostasis, hypothalamus, ghrelin, leptin, insulin, appetitive, gene variants