Given the important role of the hypothalamus in regulating feeding and metabolism, there has been considerable interest in a possible function for hypothalamic stem cells in modulating body weight in health and disease. Mice given a high-fat diet develop inflammation in the hypothalamus and lose key types of neurons. It now appears that another effect of a high-fat diet is to reduce neural stem cell numbers, as well as their ability to make new neurons — effects that are associated with activation of the IKKβ/NF-κB pathway — thereby exacerbating the primary loss of neurons and resulting in altered feeding behaviour and obesity.