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Inducible‐NOS but not neuronal‐NOS participate in the acute effect of TNF‐α on hypothalamic insulin‐dependent inhibition of food intake
Author(s) -
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.
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.07.042
Subject(s) - hypothalamus , endocrinology , medicine , nitric oxide synthase , tumor necrosis factor alpha , signal transduction , chemistry , insulin , premovement neuronal activity , biology , nitric oxide , microbiology and biotechnology , neuroscience
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.