Overexpression of Mitogen-activated protein kinase phosphatase-3 (MKP-3)reduces FoxO1 phosphorylation in mice hypothalamus

Author(s):Show less -

Rodrigues, Barbara de Almeida ^[1] ; Kuga, Gabriel Keine ^[2] ; Munoz, Vitor Rosetto ^[1] ; Gaspar, Rafael Calais ^[1] ; Tavares, Mariana Rosolen ^[1] ; Botezelli, Jose Diego ^[1] ; Ramos da Silva, Adelino Sanchez ^[3] ; Cintra, Dennys Esper ^[1] ; de Moura, Leandro Pereira ^[1] ; Simabuco, Fernando Moreira ^[1] ; Ropelle, Eduardo Rochete ^[1] ; Pauli, Jose Rodrigo ^[1]

Affiliation

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

^[2] Sao Paulo State Univ Unesp, Postgrad Program Movement Sci, Inst Biosci, Rio Claro, SP - Brazil

^[3] Univ Sao Paulo, Sch Phys Educ & Sport Ribeirao Preto, Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: Neuroscience Letters; v. 659, p. 14-17, OCT 17 2017.
• Web of Science Citations: 1

Abstract

The mitogen-activated kinase phosphatase-3 (MKP-3) has gained great importance in the scientific community by acting as a regulator of the cell cycle through dephosphorylation of FoxO1, an important transcription factor involved in the insulin intracellular signaling cascade. When dephosphorylated and translocated to the nuclei, FoxO1 can promote the transcription of orexigenic neuropeptides (NPY/AgRP) in the hypothalamus, whereas insulin signaling is responsible for the disruption of this process. However, it is not understood if the hypothalamic activation of MKP-3 affects FoxO1 phosphorylation, and we hypothesized that MKP-3 overexpression reduces the capacity of the insulin signal to phosphorylate FoxO1. In the present study, we overexpressed the DUSP6 gene through an injection of adenovirus directly into the hypothalamic third ventricle of Swiss mice. The colocalization of the adenovirus was confirmed by the immunofluorescence assay. Then, MKP-3 overexpression resulted in a significant reduction of hypothalamic FoxO1 phosphorylation after insulin stimulation. This effect was independent of changes in Akt phosphorylation. Thus, the role of MKP-3 in the hypothalamus is closely associated with FoxO1 dephosphorylation and may provide a potential therapeutic target against hypothalamic disorders related to obesity and unbalanced food intake control. (AU)

• FAPESP's process: 16/18488-8 - The role of physical exercise on molecular pathways of glucose uptake in GLUT-4 knockout mice
• Grantee: José Rodrigo Pauli
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/25512-4 - Role of physical exercise in the regulation of MKP-3 protein in the hypothalamus of obese rats: effects on insulin signaling.
• Grantee: Barbara de Almeida Rodrigues
• Support Opportunities: Scholarships in Brazil - Doctorate