Brain-derived neurotrophic factor (BDNF) suppresses food intake by acting on neurons in thehypothalamus. Here we show that BDNF-producing haematopoietic cells control appetite andenergy balance by migrating to the hypothalamic paraventricular nucleus. These haematopoietic-derived paraventricular nucleus cells produce microglial markers and make directcontacts with neurons in response to feeding status. Mice with congenital BDNF deficiency,specifically in haematopoietic cells, develop hyperphagia, obesity and insulin resistance.These abnormalities are ameliorated by bone marrow transplantation with wild-type bonemarrow cells. Furthermore, when injected into the third ventricle, wild-type bone marrowmononuclear cells home to the paraventricular nucleus and reverse the hyperphagia of BDNFdeficientmice. Our results suggest a novel mechanism of feeding control based on theproduction of BDNF by haematopoietic cells and highlight a potential new therapeutic routefor the treatment of obesity.
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