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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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| Author |
Juliana C Moraes, Maria E Amaral, Paty K Picardi, Vivian C Calegari, Talita Romanatto, Marcela Bermúdez-Echeverry, Silvana Chiavegatto, Mario J Saad, Licio A Velloso |
| Citation Information |
FEBS letters, 580:4625-31 (2006) |
| Related Products |
05-736 |
| Pub Med ID |
16876161 |
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Abstract
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.
