Inducible-NOS but not neuronal-NOS participate in the acute effect of TNF-alpha on hypothalamic insulin-dependent inhibition of food intake.
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.
Moraes
Juliana C
JC
Department of Internal Medicine, State University of Campinas, DCM-FCM, UNICAMP, 13084-970 Campinas, SP, Brazil.
Amaral
Maria E
ME
Picardi
Paty K
PK
Calegari
Vivian C
VC
Romanatto
Talita
T
Bermúdez-Echeverry
Marcela
M
Chiavegatto
Silvana
S
Saad
Mario J
MJ
Velloso
Licio A
LA
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005247:Feeding Behavior / Q000502:physiology*; D007031:Hypothalamus / Q000187:drug effects* / Q000502:physiology; D007276:Injections, Intraventricular; D007328:Insulin / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology*
D007328:Insulin; D014409:Tumor Necrosis Factor-alpha; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II