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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Body fat is increased in GM–/– mice. GM–/– and control GM+/+ male and fe...
Body fat is increased in GM–/– mice. GM–/– and control GM+/+ male and female mice were monitored from 12 to 33 weeks of age. GM–/– mice gained significantly more body weight than did age- and sex-matched GM+/+ mice (A), and GM–/– mice had increased body fat as a percentage of total body weight (B). n = 7–11; mean ± SEM. (C) Visceral and s.c. fat were visibly increased in male GM–/– mice, compared with GM+/+ control mice. (D) Weights of epididymal (EP), retroperitoneal (RE), and mesenteric (ME) fat were increased in male GM–/– mice compared with GM+/+ control mice. *P < 0.05; n = 5; mean ± SEM. Inset: M-CSF expression was decreased in GM–/– mice. M-CSF mRNA was measured by Q-PCR in mesenteric fat from GM–/– and GM+/+ male mice. M-CSF expression was reduced in GM–/– mice, compared with GM+/+ mice. (E) NPY, AgRP, POMC, and insulin receptor (IR) mRNA expression were similar in both groups, but LepR expression was increased in GM–/– hypothalamus. n = 10–11; mean ± SEM. *P < 0.05.