GM-CSF action in the CNS decreases food intake and body weight
Jacquelyn A. Reed, … , Lara S. Picard, Randy J. Seeley
Jacquelyn A. Reed, … , Lara S. Picard, Randy J. Seeley
Published November 1, 2005
Citation Information: J Clin Invest. 2005;115(11):3035-3044. https://doi.org/10.1172/JCI25681.
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Research Article Metabolism

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

Abstract

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 wild-type (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.

Authors

Jacquelyn A. Reed, Deborah J. Clegg, Kathleen Blake Smith, Emeline G. Tolod-Richer, Emily K. Matter, Lara S. Picard, Randy J. Seeley

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GM-CSF receptor immunohistochemistry. Synaptophysin (red) and GMRα immun...
GM-CSF receptor immunohistochemistry. Synaptophysin (red) and GMRα immunofluorescence (green) were localized on neurons throughout mouse brain, including ARC and PVN. (A) Only synaptophysin immunofluorescence was observed in sections when antibody serum was preincubated with the immunizing peptide to block GMRα antibody binding. (B) A section stained with GMRα immunofluorescence alone. (C) GMRα immunofluorescence was colocalized with synaptophysin immunofluorescence in the ARC (low-magnification view). (D) High-magnification view of several synaptophysin-immunoreactive neurons that did not contain GMRα. (E) High-magnification view of GMRα-positive cells surrounded by synaptophysin immunofluorescence contacts in the ARC. (F) GMRα immunofluorescence was colocalized with synaptophysin immunofluorescence in the PVN (low-magnification view). (G) High-magnification 3-dimensional reconstruction of confocal images of a single neuron from the PVN, showing colocalization of GMRα and synaptophysin immunofluorescence. Sections are representative of 5 animals in which staining was examined.