Interleukin-7, a New Cytokine Targeting the Mouse Hypothalamic Arcuate Nucleus: Role in Body Weight and Food Intake Regulation |
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Authors: | Laurence Macia Odile Viltart Myriam Delacre Christelle Sachot Laurent Héliot James P Di Santo Isabelle Wolowczuk |
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Institution: | 1. Univ Lille Nord de France, Lille, France.; 2. Laboratory of Neuroimmunoendocrinology and IFR 142, Institut Pasteur de Lille, BP 447, Lille, France.; 3. USTL, Inserm U837, JPARC, Development and Plasticity of Postnatal Brain, Lille, France.; 4. USTL, Interdisciplinary Research Institute, CNRS USR 3078, Villeneuve d''Ascq, France.; 5. Cytokines and Lymphoid Development Unit, Institut Pasteur, Paris, France.; 6. Inserm U668, Paris, France.;University of Camerino, Italy |
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Abstract: | Body weight is controlled through peripheral (white adipose tissue) and central (mainly hypothalamus) mechanisms. We have recently obtained evidence that overexpression of interleukin (IL)-7, a critical cytokine involved in lymphopoiesis, can protect against the development of diet-induced obesity in mice. Here we assessed whether IL-7 mediated its effects by modulating hypothalamic function. Acute subcutaneous injection of IL-7 prevented monosodium glutamate-induced obesity, this being correlated with partial protection against cell death in the hypothalamic arcuate nucleus (ARC). Moreover, we showed that IL-7 activated hypothalamic areas involved in regulation of feeding behavior, as indicated by induction of the activation marker c-Fos in neural cells located in the ventromedial part of the ARC and by inhibition of food intake after fasting. Both chains of the IL-7 receptor (IL-7Rα and γc) were expressed in the ARC and IL-7 injection induced STAT-3 phosphorylation in this area. Finally, we established that IL-7 modulated the expression of neuropeptides that tune food intake, with a stimulatory effect on the expression of pro-opiomelanocortin and an inhibitory effect on agouti-related peptide expression in accordance with IL-7 promoting anorectic effects. These results suggest that the immunomodulatory cytokine IL-7 plays an important and unappreciated role in hypothalamic body weight regulation. |
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