Inducible-NOS but not neuronal-NOS participate in the acute effect of TNF-α on hypothalamic insulin-dependent inhibition of food intake

• Published in: FEBS letters 2006-08, Vol.580 (19), p.4625-4631
• Main Authors: Moraes, Juliana C., Amaral, Maria E., Picardi, Paty K., Calegari, Vivian C., Romanatto, Talita, Bermúdez-Echeverry, Marcela, Chiavegatto, Silvana, Saad, Mario J., Velloso, Licio A.
• Format: Article
• Language: English
• Subjects: Animals; Cytokine; Dose-Response Relationship, Drug; Feeding Behavior - physiology; Food intake; Hypothalamus - drug effects; Hypothalamus - physiology; inducible nitric oxide synthase; Injections, Intraventricular; iNOS; Insulin; Insulin - physiology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; neuronal nitric oxide synthase; Nitric oxide; Nitric oxide synthase; Nitric Oxide Synthase Type I - metabolism; Nitric Oxide Synthase Type II - genetics; Nitric Oxide Synthase Type II - metabolism; nNOS; NOS; Rats; Rats, Wistar; TNF-α; Tumor necrosis factor; tumor necrosis factor-alpha; Tumor Necrosis Factor-alpha - administration & dosage; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2006.07.042

TNF-α acts on the hypothalamus modulating food intake and energy expenditure through mechanisms incompletely elucidated. Here, we explore the hypothesis that, to modulate insulin-induced anorexigenic signaling in hypothalamus, TNF-α requires the synthesis of NO. TNF-α activates signal transduction through JNK and p38 in hypothalamus, peaking at 10 −8 M. This is accompanied by the induction of expression of the inducible and neuronal forms of NOS, in both cases peaking at 10 −12 M. In addition, TNF-α stimulates NOS catalytic activity. Pre-treatment with TNF-α at a low dose (10 −12 M) inhibits insulin-dependent anorexigenic signaling, and this effect is abolished in iNOS but not in nNOS knockout mice.