Interleukin-7, a new cytokine targeting the mouse hypothalamic arcuate nucleus: role in body weight and food intake regulation.
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.
Macia
Laurence
L
Univ Lille Nord de France, Lille, France.
Viltart
Odile
O
Delacre
Myriam
M
Sachot
Christelle
C
Héliot
Laurent
L
Di Santo
James P
JP
Wolowczuk
Isabelle
I
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
D015851:Interleukin-7; D020395:Receptors, Interleukin-7; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse