Acute physical exercise increases APPL1/PI3K signaling in the hypothalamus of lean mice

急性体力锻炼可增强瘦小鼠下丘脑中的 APPL1/PI3K 信号

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作者:Rafael Calais Gaspar, Vitor Rosetto Muñoz, Gabriel Keine Kuga, Susana Castelo Branco Ramos Nakandakari, Barbara Moreira Crisol, Luciene Lenhare, Leonardo Breda, José Diego Botezelli, Marcella Ramos Sant'Ana, Adelino S R da Silva, Dennys Esper Cintra, Leandro Pereira de Moura, Eduardo Rochete Ropelle

Abstract

Adiponectin is an adipokine that acts in the control of energy homeostasis. The adaptor protein containing the pleckstrin homology domain, phosphotyrosine-binding domain, and leucine zipper motif 1 (APPL1) is a key protein in the adiponectin signaling. The APPL1 mediates a positive effect on the insulin signaling through the interaction with the phosphoinositide 3-kinase (PI3K). Thus, the present study aimed to explore the effects of an acute physical exercise session on the hypothalamic adiponectin signaling. Firstly, using bioinformatics analysis, we found a negative correlation between hypothalamic APPL1 mRNA levels and food consumption in several strains of genetically diverse BXD mice. Also, the mice and the human database revealed a positive correlation between the levels of APPL1 mRNA and PI3K mRNA. At the molecular level, the exercised mice showed increased APPL1 and PI3K (p110) protein contents in the hypothalamus of Swiss mice. Furthermore, the exercise increases co-localization between APPL1 and PI3K p110 predominantly in neurons of the arcuate nucleus of hypothalamus (ARC). Finally, we found an acute exercise session reduced the food intake 5 hr after the end of fasting. In conclusion, our results indicate that physical exercise reduces the food intake and increases some proteins related to adiponectin pathway in the hypothalamus of lean mice.

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