title: Interleukin-7, a new cytokine targeting the mouse hypothalamic arcuate nucleus: role in body weight and food intake regulation.
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-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.
authors.affiliation: Univ Lille Nord de France, Lille, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Macia
authors.forename: Odile
authors.initials: O
authors.lastname: Viltart
authors.forename: Myriam
authors.initials: M
authors.lastname: Delacre
authors.forename: Christelle
authors.initials: C
authors.lastname: Sachot
authors.forename: Laurent
authors.initials: L
authors.lastname: Héliot
authors.forename: James P
authors.initials: JP
authors.lastname: Di Santo
authors.forename: Isabelle
authors.initials: I
authors.lastname: Wolowczuk
mesh_terms: D000818:Animals; D001069:Appetite Regulation / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D015851:Interleukin-7 / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D009474:Neurons / Q000737:chemistry / Q000187:drug effects; D009765:Obesity / Q000139:chemically induced / Q000517:prevention & control; D010766:Phosphorylation / Q000187:drug effects; D020395:Receptors, Interleukin-7 / Q000032:analysis; D050796:STAT3 Transcription Factor / Q000378:metabolism
chemical_list: D015851:Interleukin-7; D020395:Receptors, Interleukin-7; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse