Acute exercise suppresses hypothalamic PTP1B protein level and improves insulin and leptin signaling in obese rats

Author(s):Show less -

Chiarreotto-Ropelle, Eloize C. ^[1] ; Pauli, Luciana S. S. ^[1] ; Katashima, Carlos K. ^[2] ; Pimentel, Gustavo D. ^[2] ; Picardi, Paty K. ^[2] ; Silva, Vagner R. R. ^[1] ; de Souza, Claudio T. ^[3] ; Prada, Patricia O. ^[1] ; Cintra, Dennys E. ^[1] ; Carvalheira, Jose B. C. ^[2] ; Ropelle, Eduardo R. ^{[2, 1]} ; Pauli, Jose R. ^[1]

Affiliation

^[1] Univ Estadual Campinas, UNICAMP, Sch Appl Sci, Limeira, SP - Brazil

^[2] Univ Estadual Campinas, Fac Med Sci, Dept Internal Med, Campinas, SP - Brazil

^[3] Univ Southern Santa Catarina, Criciuma, SC - Brazil

• Document type: Journal article
• Source: AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM; v. 305, n. 5, p. E649-E659, SEP 2013.
• Web of Science Citations: 24

Abstract

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 that is responsible for the central insulin and leptin resistance. 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 (IR beta and IRS-1) and leptin (JAK2) signaling, increased the tyrosine phosphorylation of these molecules, and restored 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 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. (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
• FAPESP's process: 11/13779-0 - Effects of physical exercise on the MKP-3/FoxO1 association in liver of obese and diabetic mice
• Grantee: Luciana Santos Souza Pauli
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 10/12091-2 - Effects of physical training on inflammatory and apoptotic process in hypothalamic neurons of hungry control in high-fat diet-induced obese mice
• Grantee: José Rodrigo Pauli
• Support Opportunities: Regular Research Grants