Knocking down amygdalar PTP1B in diet-induced obese rats improves insulin signaling/action, decreases adiposity and may alter anxiety behavior

Autor(es)

Mendes, Natalia Ferreira ; Castro, Gisele ; Guadagnini, Dioze ; Tobar, Natalia ; Cognuck, Susana Quiros ; Kagohara Elias, Lucila Leico ; Boer, Patricia Aline ; Prada, Patricia Oliveira

• Tipo de documento: Artigo Científico
• Fonte: METABOLISM-CLINICAL AND EXPERIMENTAL; v. 70, p. 1-11, MAY 2017.
• Citações Web of Science: 7

Resumo

Objective. Protein tyrosine phosphatase 1B (PTP1B) has been extensively implicated in the regulation of body weight, food intake, and energy. expenditure. The role of PTP1B appears to be cell and brain region dependent. Results. Herein, we demonstrated that chronic high-fat feeding enhanced PTP1B expression in the central nucleus of the amygdala (CeA) of rats compared to rats on chow: Knocking down PTP1B with oligonucleotide antisense (ASO) decreased its expression and was sufficient to improve the anorexigenic effect of insulin through IR/Akt signaling in the CeA. ASO treatment reduces body weight, fat mass, serum leptin levels, and food intake and also increases energy expenditure, without altering ambulatory activity. These changes were explained, at least in part, by the improvement of insulin sensitivity in the CeA, decreasing NPY and enhancing oxytocin expression. There was a slight decline in fasting blood glucose and serum insulin levels possibly due to leanness in rats treated with ASO. Surprisingly, the elevated plus maze test revealed an anxiolytic behavior after reduction of PTP1B in the CeA. Conclusions. Thus, the present study highlights the deleterious role that the amygdalar PTP1B has on energy homeostasis in obesity states. The reduction of PTP1B in the CeA may be a strategy for the treatment of obesity, insulin resistance and anxiety disorders. (C) 2017 Elsevier Inc. All rights reserved. (AU)

• Processo FAPESP: 15/00343-0 - Efeito da obesidade na regulação da AMPK em amígdala: implicações no metabolismo energético
• Beneficiário: Patrícia de Oliveira Prada
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/07607-8 - CMPO - Centro Multidisciplinar de Pesquisa em Obesidade e Doenças Associadas
• Beneficiário: Licio Augusto Velloso
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs