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. © 2006 Federation of European Biochemical Societies.
Moraes, J. C., Amaral, M. E., Picardi, P. K., Calegari, V. C., Romanatto, T., Bermúdez-Echeverry, M., … Velloso, L. A. (2006). Inducible-NOS but not neuronal-NOS participate in the acute effect of TNF-α on hypothalamic insulin-dependent inhibition of food intake. FEBS Letters, 580(19), 4625–4631. https://doi.org/10.1016/j.febslet.2006.07.042