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FEBS Lett. 2006 Aug 21;580(19):4625-31. Epub 2006 Jul 21.

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

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  • 1Department of Internal Medicine, State University of Campinas, DCM-FCM, UNICAMP, 13084-970 Campinas, SP, Brazil.


TNF-alpha 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-alpha requires the synthesis of NO. TNF-alpha 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-alpha stimulates NOS catalytic activity. Pre-treatment with TNF-alpha 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.

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