Control of obesity and glucose intolerance via building neural stem cells in the hypothalamus

Neural stem cells (NSCs) were recently revealed to exist in the hypothalamus of adult mice. Here, following our observation showing that a partial loss of hypothalamic NSCs caused weight gain and glucose intolerance, we studied if NSCs-based cell therapy could be developed to control these disorders. While hypothalamus-implanted NSCs failed to survive in mice with obesity, NF-κB inhibition induced survival and neurogenesis of these cells, leading to effects in counteracting obesity and glucose intolerance. To generate an alternative cell source, we revealed that iPS-derived NSCs were converted into htNSCs by neuropeptide treatment. Of note, obesity condition potentiated the transfer of carotid artery-injected NSCs into the hypothalamus. These iPS-derived cells when engineered with NF-κB inhibition were also effective in reducing obesity and glucose intolerance, and neurogenesis towards POMCergic and GABAergic lineages was accountable. In conclusion, building NSCs in the hypothalamus represents a strategy for controlling obesity and glucose disorders.