Modulation of hypothalamic PTP1B in the TNF-alpha-induced insulin and leptin resistance.
We have associated functional and molecular studies of insulin and leptin to investigate the effect of TNF-alpha on central insulin and leptin signaling in rats pre-treated with PTP1B-ASO. The icv infusion of TNF-alpha-induced an increase in PTP1B protein expression and activity, and attenuated insulin and leptin sensitivity and signaling in the hypothalamus. However, TNF-alpha was able to completely blunt the leptin and insulin effect in rats treated with PTP1B-ASO, suggesting that TNF-alpha does not require PTP1B to fully attenuate the leptin and insulin effects. In addition, our data also show that other mechanisms of insulin and leptin resistance are activated in the hypothalamus by TNF-alpha.
Picardi
Paty Karoll
PK
Departamento de Clínica Médica, FCM, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil.
Caricilli
Andrea Moro
AM
de Abreu
Lélia Lelis Ferreira
LL
Carvalheira
José Barreto Campello
JB
Velloso
Lício Augusto
LA
Saad
Mário José Abdalla
MJ
D000818:Animals; D006728:Hormones / Q000378:metabolism / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D007155:Immunologic Factors / Q000378:metabolism / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D020738:Leptin / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology*
D006728:Hormones; D007155:Immunologic Factors; D007328:Insulin; D020738:Leptin; D014409:Tumor Necrosis Factor-alpha