Characterization of hypothalamic PTP1B activity in obese rodents submited to physical exercise

Author(s)

Eloize Cristina Chiarreotto Ropelle

• Document type: Master's Dissertation
• Press: Limeira, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Aplicadas
• Defense date: 2013-07-29

Examining board members

José Rodrigo Pauli; Fúlvia de Barros Manchado Gobatto; Claudio Teodoro de Souza

• Advisor: José Rodrigo Pauli

Abstract

The food intake and energy expenditure are regulated by specific neurons in the hypothalamus. The proper functioning of this complex neuronal network is crucial to the maintenance of energy homeostasis in mammals. However, hypothalamic inflammation is associated with insulin and leptin resistance, hyperphagia and obesity. In this scenario, hypothalamic protein tyrosine phosphatase 1B (PTP1B) has emerged as the key phosphatase induced by inflammation responsible for the central insulin and leptin resistance. The aim of this study was evaluate the effects of exercise on PTP1B activity in the hypothalamus of obese rodents. Here, we demonstrated that acute exercise reduced inflammation and PTP1B protein level/activity in the hypothalamus of obese rodents. Exercise disrupted the interaction between PTP1B with proteins involved in the early steps of insulin (IRbeta and IRS1) and leptin (Jak2) signaling, increased the anorexigenic effects of insulin and leptin in obese rats. Interestingly, the anti-inflammatory action and the reduction of PTP1B activity mediated by exercise occurred in an Interleukin-6 (IL-6)-dependent manner, because exercise failed to reduce inflammation and PTP1B protein level after the disruption of hypothalamic-specific IL-6 action in obese rats. Conversely, intracerebroventricular (ICV) administration of recombinant IL-6 reproduced the effects of exercise, improving hypothalamic insulin and leptin action by reducing the inflammatory signaling and PTP1B activity in obese rats at rest. Taken together, our study reports that physical exercise restores insulin and leptin signaling, at least in part, by reducing hypothalamic PTP1B protein level through the central anti-inflammatory response mediate by IL-6 (AU)

• FAPESP's process: 11/14727-4 - Characterization of hypothalamic PTP1B activity in obese rodents submited to physical exercise.
• Grantee: Eloize Cristina Chiarreotto Ropelle
• Support Opportunities: Scholarships in Brazil - Master