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The Anorectic Actions of the TGFbeta Cytokine MIC-1/GDF15 Require an Intact Brainstem Area Postrema and Nucleus of the Solitary Tract

Abstract

Macrophage inhibitory cytokine-1 (MIC-1/GDF15) modulates food intake and body weight under physiological and pathological conditions by acting on the hypothalamus and brainstem. When overexpressed in disease, such as in advanced cancer, elevated serum MIC-1/GDF15 levels lead to an anorexia/cachexia syndrome. To gain a better understanding of its actions in the brainstem we studied MIC-1/GDF15 induced neuronal activation identified by induction of Fos protein. Intraperitoneal injection of human MIC-1/GDF15 in mice activated brainstem neurons in the area postrema (AP) and the medial (m) portion of the nucleus of the solitary tract (NTS), which did not stain with tyrosine hydroxylase (TH). To determine the importance of these brainstem nuclei in the anorexigenic effect of MIC-1/GDF15, we ablated the AP alone or the AP and the NTS. The latter combined lesion completely reversed the anorexigenic effects of MIC-1/GDF15. Altogether, this study identified neurons in the AP and/or NTS, as being critical for the regulation of food intake and body weight by MIC-1/GDF15.

Type Journal
ISBN 1932-6203 (Electronic) 1932-6203 (Linking)
Authors Tsai, V. W.; Manandhar, R.; Jorgensen, S. B.; Lee-Ng, K. K.; Zhang, H. P.; Marquis, C. P.; Jiang, L.; Husaini, Y.; Lin, S.; Sainsbury, A.; Sawchenko, P. E.; Brown, D. A.; Breit, S. N.;
Publisher Name PLoS ONE
Published Date 2014-01-01 00:00:00
Published Volume 9
Published Issue 6
Published Pages e100370
URL http://www.ncbi.nlm.nih.gov/pubmed/24971956
Status Published In-print
OpenAccess Link https://publications.gimr.garvan.org.au/download.php?12466_12798/pone.0100370.pdf