Aerobic training improves NAFLD markers and insulin resistance through AMPK-PPAR-α signaling in obese mice
| Autor: | Camila Oliveira de Souza, José Cesar Rosa Neto, Tiego A. Diniz, Lucas Ariel Fernandes da Rocha, Iuri Cordeiro Valadão, Alexandre Abilio de Souza Teixeira, Luana A Biondo, Loreana Sanches Silveira, Carol Cabral-Santos, Edson Alves de Lima Junior |
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| Přispěvatelé: | Universidade de São Paulo (USP), University of the State of Sao Paulo |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Hepatic steatosis AMPK and inflammation CD36 Peroxisome proliferator-activated receptor Mice Obese Inflammation AMP-Activated Protein Kinases 030226 pharmacology & pharmacy General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Liver disease Mice 0302 clinical medicine Insulin resistance Downregulation and upregulation Non-alcoholic Fatty Liver Disease Internal medicine Physical Conditioning Animal NAFLD medicine Aerobic exercise Animals PPAR alpha Obesity General Pharmacology Toxicology and Pharmaceutics Exercise chemistry.chemical_classification biology business.industry AMPK EXPRESSÃO GÊNICA General Medicine medicine.disease Mice Inbred C57BL 030104 developmental biology Endocrinology chemistry Liver biology.protein Cytokines medicine.symptom Insulin Resistance business Biomarkers Signal Transduction |
| Zdroj: | Scopus Repositório Institucional da UNESP Universidade Estadual Paulista (UNESP) instacron:UNESP Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| Popis: | Made available in DSpace on 2022-04-28T19:29:51Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-02-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) 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. Immunometabolism Research Group Department of Cell and Developmental Biology University of São Paulo, Avenida Prof Lineu Prestes, 1524 Institute of Biomedical Sciences University of Sao Paulo Exercise and Immunometabolism Research Group Department of Physical Education University of the State of Sao Paulo, Rua Roberto Simonsen, 305 FAPESP: 2016/02696-0 FAPESP: 2019/09854-9 |
| Databáze: | OpenAIRE |
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