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.