Interleukin-7, a New Cytokine Targeting the Mouse Hypothalamic Arcuate Nucleus: Role in Body Weight and Food Intake Regulation

University of Camerino, Italy
PLoS ONE (Impact Factor: 3.23). 04/2010; 5(4):e9953. DOI: 10.1371/journal.pone.0009953
Source: PubMed


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-7Ralpha and gamma(c)) 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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Available from: Isabelle Wolowczuk,
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    • "At that stage of our work, we hypothesized that IL-7 might impact on WAT mass increase and metabolic dysfunctions associated with the development of obesity, such as insulin and glucose intolerance. A protective role of IL-7 against obesity and insulin resistance has been suggested in IL-7-treated mice after pharmacological destruction of hypothalamus by monosodium glutamate [24] or gold thioglucose (IW, unpublished observation). Thus we assessed the consequences of a single subcutaneous injection of recombinant murine IL-7 in the more pathophysiological model of high-fat diet (HFD)-induced obesity. "
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