The anorectic actions of the TGFβ cytokine MIC-1/GDF15 require an intact brainstem area postrema and nucleus of the solitary tract

Vicky Wang Wei Tsai, Rakesh Manandhar, Sebastian Beck Jrøgensen, Ka Ki Michelle Lee-Ng, Hong Ping Zhang, Christopher Peter Marquis, Lele Jiang, Yasmin Husaini, Shu Lin, Amanda Sainsbury, Paul E. Sawchenko, David A. Brown, Samuel N. Breit

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88 Citations (Scopus)

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.

Original languageEnglish
Article numbere100370
JournalPLoS One
Volume9
Issue number6
DOIs
Publication statusPublished - 27 Jun 2014
Externally publishedYes

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