GM-CSF action in the CNS decreases food intake and body weight

Many proinflammatory cytokines, such as leptin, play key roles in dynamic regulation of energy expenditure and food intake. The present work tested a role for the proinflammatory cytokine GM-CSF. Central but not peripheral administration of GM-CSF to adult rats significantly decreased food intake and body weight for at least 48 hours. Similar results were observed following central administration of GM-CSF in mice. GM-CSF receptor immunoreactivity was found on neurons within the paraventricular and arcuate nuclei of the hypothalamus. GM-CSF-deficient (GM(-/-)) mice weighed more and had significantly higher total body fat than wildtype (GM(+/+)) mice. Energy expenditure in GM-/- mice was decreased compared with that in GM(+/+) mice. Taken together, these findings demonstrate that GM-CSF signaling in the CNS can regulate energy homeostasis.