Interleukin-7, a new cytokine targeting the mouse hypothalamic arcuate nucleus: role in body weight and food intake regulation

• Published in: PloS one 2010-04, Vol.5 (4), p.e9953
• Main Authors: Macia, Laurence, Viltart, Odile, Delacre, Myriam, Sachot, Christelle, Héliot, Laurent, Di Santo, James P, Wolowczuk, Isabelle
• Format: Article
• Language: English
• Subjects: Adipose tissue; Animals; Appetite Regulation - drug effects; Arcuate nucleus; Body weight; Body Weight - drug effects; Brain; Brain Chemistry - drug effects; Brain research; c-Fos protein; Cell death; Cognitive science; Cytokines; Diabetes and Endocrinology/Endocrinology; Diabetes and Endocrinology/Neuroendocrinology and Pituitary; Diabetes and Endocrinology/Obesity; Evaluation; Feeding behavior; Food; Food intake; Fos protein; Gene expression; Glutamate; Histology; Homeostasis; Hypothalamus; Hypothalamus - cytology; Hypothalamus - drug effects; Hypothalamus - physiology; Immunomodulation; Injection; Insulin resistance; Interleukin 7; Interleukin-7 - administration & dosage; Interleukin-7 - pharmacology; Interleukins; Kinases; Laboratories; Lymphocytes; Lymphopoiesis; Melanocyte stimulating hormone; Metabolism; Mice; Monosodium glutamate; Nervous system; Neurons - chemistry; Neurons - drug effects; Neuropeptides; Neurosciences; Nuclei (cytology); Obesity; Obesity - chemically induced; Obesity - prevention & control; Phosphorylation; Phosphorylation - drug effects; Physiology; Proopiomelanocortin; Proteins; Receptors, Interleukin-7 - analysis; Rodents; Skin; Skin diseases; Stat3 protein; STAT3 Transcription Factor - metabolism; Tumor necrosis factor-TNF; Weight control
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0009953

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.