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Updated: Jun 12, 2026

Differentiated Mouse Adipocytes in Primary Culture: A Model of Insulin Resistance
Published on: February 17, 2023
Modulation of hypothalamic PTP1B in the TNF-alpha-induced insulin and leptin resistance
Paty Karoll Picardi1, Andrea Moro Caricilli, Lélia Lelis Ferreira de Abreu
1Departamento de Clínica Médica, FCM, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil.
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.
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.
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