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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Figure 1

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i3vt injection of rat GM-CSF in rats. (A) Rats received a single injecti...
i3vt injection of rat GM-CSF in rats. (A) Rats received a single injection of 0.03, 0.06, or 0.6 μg recombinant rat GM-CSF, or vehicle (Veh) alone. Twenty-four-hour food intake was significantly decreased in rats receiving 0.6 μg GM-CSF. (B) Change in body weight at 24 hours after injection was significantly greater in rats receiving 0.6 μg GM-CSF. (C) Rats were injected with 0.6 μg GM-CSF or vehicle. GM-CSF treatment significantly suppressed food intake at 4 hours, compared with vehicle treatment. (D) Rats were injected with 0.6 μg rat GM-CSF or recombinant human GM-CSF (hGM). While 24-hour food intake was suppressed with rat GM-CSF, human GM-CSF–treated rats did not differ from vehicle-treated rats. (E) Rats were injected with 0.6 μg GM-CSF or vehicle, followed by a 24-hour fast (day 1). Weight loss at 24 hours after injection was greater in rats injected with GM-CSF compared with vehicle. (F) When food was returned, anorexia persisted for an additional 24 hours (day 2). For all rat studies, n = 7–9; error bars show mean ± SEM. Twenty-four-hour food intake (G) and body weight (H) were decreased in mice receiving 1 μg mouse GM-CSF, compared with those receiving vehicle. n = 5–6; mean ± SEM. *P < 0.05.