Tumor necrosis factor-alpha activates signal transduction in hypothalamus and modulates the expression of pro-inflammatory proteins and orexigenic/anorexigenic neurotransmitters.
Tumor necrosis factor-alpha (TNF-alpha) is known to participate in the wastage syndrome that accompanies cancer and severe infectious diseases. More recently, a role for TNF-alpha in the pathogenesis of type 2 diabetes mellitus and obesity has been shown. Much of the regulatory action exerted by TNF-alpha upon the control of energy stores depends on its action on the hypothalamus. In this study, we show that TNF-alpha activates canonical pro-inflammatory signal transduction pathways in the hypothalamus of rats. These signaling events lead to the transcriptional activation of an early responsive gene and to the induction of expression of cytokines and a cytokine responsive protein such as interleukin-1beta, interleukin-6, interleukin-10 and suppressor of cytokine signalling-3, respectively. In addition, TNF-alpha induces the expression of neurotransmitters involved in the control of feeding and thermogenesis. Thus, TNF-alpha may act directly in the hypothalamus inducing a pro-inflammatory response and the modulation of expression of neurotransmitters involved in energy homeostasis.
Amaral
Maria E
ME
Department of Internal Medicine, State University of Campinas, Sao Paulo, Brazil.
Barbuio
Raquel
R
Milanski
Marciane
M
Romanatto
Talita
T
Barbosa
Helena C
HC
Nadruz
Wilson
W
Bertolo
Manoel B
MB
Boschero
Antonio C
AC
Saad
Mario J A
MJ
Franchini
Kleber G
KG
Velloso
Licio A
LA
D000818:Animals; D001522:Behavior, Animal; D015153:Blotting, Western / Q000379:methods; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004347:Drug Interactions / Q000502:physiology; D004435:Eating / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D017930:Genes, Reporter / Q000502:physiology; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D007276:Injections, Intraventricular / Q000379:methods; D007328:Insulin / Q000494:pharmacology; D008297:Male; D018377:Neurotransmitter Agents / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction / Q000187:drug effects*; D014162:Transfection / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage*
D016207:Cytokines; D007328:Insulin; D018377:Neurotransmitter Agents; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha