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

Author(s)

Diniz, Tiego Aparecido ^[1] ; de Lima Junior, Edson Alves ^[1] ; Teixeira, Alexandre Abilio ^[1] ; Biondo, Luana Amorim ^[1] ; Fernandes Rocha, Lucas Ariel ^[2] ; Valadao, Iuri Cordeiro ^[2] ; Silveira, Loreana Sanches ^[1] ; Cabral-Santos, Carol ^[3] ; de Souza, Camila Oliveira ^[1] ; Rosa Neto, Jose Cesar ^[1]

Affiliation

^[1] Univ Sao Paulo, Dept Cell & Dev Biol, Immunometab Res Grp, Ave Prof Lineu Prestes 1524, BR-05508900 Butanta, SP - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Sao Paulo, SP - Brazil

^[3] Univ State Sao Paulo, Dept Phys Educ, Exercise & Immunometab Res Grp, Rua Roberto Simonsen 305, BR-19060900 Presidente Prudente, SP - Brazil

• Document type: Journal article
• Source: Life Sciences; v. 266, FEB 1 2021.
• Web of Science Citations: 1

Abstract

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 nonesterified 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-alpha protein expression. Moreover, although no effects of intervention in PPAR-gamma protein concentration were observed, we found increased levels of its target genes Cd36 and Scdl in exercised group, demonstrating augmented transcriptional activity. AT reduced liver cytokines concentrations, such as TNF-alpha, IL-10, MCP-1 and IL-6, regardless of increased 5er536 NF-kappa B phosphorylation. In fact, none of the interventions regulated NF-kappa B 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-alpha signaling and PPAR-gamma activation, respectively, improving insulin resistance in obese mice. (AU)

• FAPESP's process: 19/09854-9 - Effect of doxorubicin upon the adipose tissue: elucidation the role of PPARs family
• Grantee: José Cesar Rosa Neto
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/02696-0 - Assessment of the anti-inflammatory effects of endurance training in adipose tissue: the possible mediating role of adiponectin
• Grantee: Tiego Aparecido Diniz
• Support Opportunities: Scholarships in Brazil - Doctorate