Background. The global obesity problem supports the urgent need for research that aims to understand the basic mechanisms that regulate food intake, appetite and body weight: 1) Over-nutrition: the most urgent public health issue in the Western world. It increases the prevalence of multiple chronic diseases via the metabolic consequences of obesity. In the obese population, the mean age of death is now falling, reversing decades of progressively increased longevity for all citizens. However, the mean age of the total population is rising. 2) Malnutrition. In contrast to obesity, malnutrition is one of the greatest threats to the health and well being, especially of older adults. Age related weight loss is driven by reductions in energy intake and appetite, which are only partly balanced by decreases in energy expenditure. The information available for the biochemical processes that control hunger and satiety is still insufficient. The accurate matching of calorie consumption to calorie expenditure involves a complex interplay among a number of organ systems. There is new evidence that fuel sensing occurs in a number of peripheral cell types, which include specific taste receptors in the gut. Some of these cells can produce neural or humoral signals that act on the brain to impact energy balance. In addition to these peripheral sensor systems, specialized neurons within the CNS can also directly sense fuel status. There is ample evidence documenting that links levels of glucose to specific populations of neurons in the CNS that are likely to modulate appetite and energy balance. Finally, there is increasing evidence that links these fuel sensors to key signals of stored energy in the adipose tissue (example: leptin). Thus a critical question is to identify the mechanisms by which signals of fuel are integrated in the CNS.