Aerobic training improves NAFLD markers and insulin resistance through AMPK-PPAR-α signaling in obese mice.

Autor: Diniz TA; Immunometabolism Research Group, Department of Cell and Developmental Biology, University of São Paulo, Avenida Prof Lineu Prestes, 1524, CEP 05508-900 Butantã, São Paulo, Brazil., de Lima Junior EA; Immunometabolism Research Group, Department of Cell and Developmental Biology, University of São Paulo, Avenida Prof Lineu Prestes, 1524, CEP 05508-900 Butantã, São Paulo, Brazil., Teixeira AA; Immunometabolism Research Group, Department of Cell and Developmental Biology, University of São Paulo, Avenida Prof Lineu Prestes, 1524, CEP 05508-900 Butantã, São Paulo, Brazil., Biondo LA; Immunometabolism Research Group, Department of Cell and Developmental Biology, University of São Paulo, Avenida Prof Lineu Prestes, 1524, CEP 05508-900 Butantã, São Paulo, Brazil., da Rocha LAF; Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil., Valadão IC; Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil., Silveira LS; Immunometabolism Research Group, Department of Cell and Developmental Biology, University of São Paulo, Avenida Prof Lineu Prestes, 1524, CEP 05508-900 Butantã, São Paulo, Brazil., Cabral-Santos C; Exercise and Immunometabolism Research Group, Department of Physical Education, University of the State of Sao Paulo, Rua Roberto Simonsen, 305, 19060-900 Presidente Prudente, SP, Brazil., de Souza CO; Immunometabolism Research Group, Department of Cell and Developmental Biology, University of São Paulo, Avenida Prof Lineu Prestes, 1524, CEP 05508-900 Butantã, São Paulo, Brazil., Rosa Neto JC; Immunometabolism Research Group, Department of Cell and Developmental Biology, University of São Paulo, Avenida Prof Lineu Prestes, 1524, CEP 05508-900 Butantã, São Paulo, Brazil. Electronic address: jrosaneto@usp.br.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2021 Feb 01; Vol. 266, pp. 118868. Date of Electronic Publication: 2020 Dec 10.
DOI: 10.1016/j.lfs.2020.118868
Abstrakt: Liver steatosis is one of the main drivers for the development of whole-body insulin resistance. Conversely, aerobic training (AT) has been suggested as non-pharmacological tool to improve liver steatosis, however, the underlying molecular mechanism remains unclear. Therefore, the aim of this study was to analyze the effect of 8-weeks AT in non-alcoholic liver disease (NAFLD) outcomes in obese mice. Male C57BL/6 J wild type (WT) were fed with standard (SD) or high-fat diet (HFD) for 12-weeks. Another group fed with HFD underwent 8-weeks of AT (60% of maximum velocity), initiated at the 5th week of experimental protocol. We measured metabolic, body composition parameters, protein and gene expression inflammatory and metabolic mediators. We found that AT attenuates the weight gain, but not body fat accumulation. AT improved triacylglycerol and non-esterified fatty acid plasma concentrations, and also whole-body insulin resistance. Regarding NAFLD, AT decreased the progression of macrovesicular steatosis and inflammation through the upregulation of AMPK Thr172 phosphorylation and PPAR-α protein expression. Moreover, although no effects of intervention in PPAR-γ protein concentration were observed, we found increased levels of its target genes Cd36 and Scd1 in exercised group, demonstrating augmented transcriptional activity. AT reduced liver cytokines concentrations, such as TNF-α, IL-10, MCP-1 and IL-6, regardless of increased Ser536 NF-κB phosphorylation. In fact, none of the interventions regulated NF-κB target genes Il1b and Cccl2, demonstrating its low transcriptional activity. Therefore, we conclude that AT attenuates the progression of liver macrovesicular steatosis and inflammation through AMPK-PPAR-α signaling and PPAR-γ activation, respectively, improving insulin resistance in obese mice.
(Copyright © 2020. Published by Elsevier Inc.)
Databáze: MEDLINE
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