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

FEBS Lett. 2006 Aug 21;580(19):4625-31. doi: 10.1016/j.febslet.2006.07.042. Epub 2006 Jul 21.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Feeding Behavior / physiology*
  • Hypothalamus / drug effects*
  • Hypothalamus / physiology
  • Injections, Intraventricular
  • Insulin / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nitric Oxide Synthase Type I / metabolism*
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism*
  • Rats
  • Rats, Wistar
  • Tumor Necrosis Factor-alpha / administration & dosage
  • Tumor Necrosis Factor-alpha / pharmacology*


  • Insulin
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide Synthase Type I
  • Nitric Oxide Synthase Type II