Endurance exercise training increases APPL1 expression and improves insulin signaling in the hepatic tissue of diet-induced obese mice, independently of weight loss

Endurance exercise training increases APPL1 expression and improves insulin signaling in the hepatic tissue of diet-induced obese mice, independently of weight loss

Author Marinho, Rodolfo Autor UNIFESP Google Scholar
Ropelle, Eduardo Rochete Google Scholar
Cintra, Dennys Esper Google Scholar
De Souza, Cláudio Teodoro Google Scholar
Da Silva, Adelino Sanchez Ramos Google Scholar
Bertoli, Flávia Cronéis Autor UNIFESP Google Scholar
Colantonio, Emilson Autor UNIFESP Google Scholar
D'Almeida, Vânia Autor UNIFESP Google Scholar
Pauli, José Rodrigo Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Universidade Estadual de Campinas (UNICAMP)
Univ Extremo Sul Catarinense
Universidade de São Paulo (USP)
Abstract Hepatic insulin resistance is the major contributor to fasting hyperglycemia in type 2 diabetes. the protein kinase Akt plays a central role in the suppression of gluconeogenesis involving forkhead box O1 (Foxo1) and peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1a), and in the control of glycogen synthesis involving the glycogen synthase kinase beta (GSK3 beta) in the liver. It has been demonstrated that endosomal adaptor protein APPL1 interacts with Akt and blocks the association of Akt with its endogenous inhibitor, tribbles-related protein 3 (TRB3), improving the action of insulin in the liver. Here, we demonstrated that chronic exercise increased the basal levels and insulin-induced Akt serine phosphorylation in the liver of diet-induced obese mice. Endurance training was able to increase APPL1 expression and the interaction between APPL1 and Akt. Conversely, training reduced both TRB3 expression and TRB3 and Akt association. the positive effects of exercise on insulin action are reinforced by our findings that showed that trained mice presented an increase in Foxo1 phosphorylation and Foxo1/PGC-1a association, which was accompanied by a reduction in gluconeogenic gene expressions (PEPCK and G6Pase). Finally, exercised animals demonstrated increased at basal and insulin-induced GSK3 beta phosphorylation levels and glycogen content at 24?h after the last session of exercise. Our findings demonstrate that exercise increases insulin action, at least in part, through the enhancement of APPL1 and the reduction of TRB3 expression in the liver of obese mice, independently of weight loss. J. Cell. Physiol. 227: 29172926, 2012. (C) 2011 Wiley Periodicals, Inc.
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number FAPESP: 2010/04290-5
Date 2012-07-01
Published in Journal of Cellular Physiology. Malden: Wiley-Blackwell, v. 227, n. 7, p. 2917-2926, 2012.
ISSN 0021-9541 (Sherpa/Romeo, impact factor)
Publisher Wiley-Blackwell
Extent 2917-2926
Origin http://dx.doi.org/10.1002/jcp.23037
Access rights Closed access
Type Article
Web of Science ID WOS:000301709700015
URI http://repositorio.unifesp.br/handle/11600/35036

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