Evaluation of acute and chronic effects of physical exercise on skeletal muscle and liver in mice submitted to standard and high-fat diet: the role of AMPK.

Author(s)

Tiego Aparecido Diniz

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2021-12-10

Examining board members

José Cesar Rosa Neto; Érico Chagas Caperuto; Daniela Caetano Gonçalves; Lila Missae Oyama

• Advisor: José Cesar Rosa Neto

Abstract

The AMP-activated protein kinase (AMPK) has been identified as one of the main links between physical exercise and metabolic health, however, its role during acute and chronic physical exercise still not fully elucidated. Thus, the objectives of the present study were: i) to evaluate the participation of AMPK in the absence and presence of adiponectin after an acute exercise session and; ii) to evaluate the role of AMPK in improving fatty liver parameters after 8 weeks of aerobic training. For this, C57BL/6 mice (WT) and adiponectin knockout (AdKO) were used in two different experimental designs. In the first, WT and AdKO animals were divided into exercise and sedentary groups. Subsequently, the groups were subdivided into 2 and 24 hours after acute physical exercise, along with their sedentary peers. For the second experimental design, WT animals were divided into three groups, standard diet (SD), high-fat diet (HFD) and high-fat diet associated with 8 weeks of aerobic training (HFD+T). For the first experimental design, the glycogen content was increased in AdKO animals (p value = 0.005). In the WT group, an increase in AMPK phosphorylation was found 2 hours after exercise, returning to the basal level 24 hours later. Confirming AMPK activation, acetyl-CoA carboxylase (Ser79) phosphorylation was increased 2 hours after exercise and returned to baseline 24 hours later, outcomes that were not observed in AdKO mice. In the WT group, IL-10 and 1L-6 concentrations were increased 2 hours (p-value <0.01) and 24 hours (p-value <0.001) after exercise when compared to the AdKO group. For the second experimental design, the HFD+T group showed improvement in plasma lipid levels and insulin resistance. Regarding non-alcoholic fatty liver disease markers, it was found that the progression of macrovesicular steatosis and inflammation was decreased in the HFD+T group, concomitantly with the increase in AMPK phosphorylation (Thr172) and PPAR- protein expression, as well as its target genes Acox and Cpt1a. Furthermore, an increase in the gene expression of PPAR- target genes was found, such as Cd36 and Scd1. In the HFD+T group, the concentration of hepatic cytokines such as TNF-, IL-10, MCP-1 and IL-6 was reduced, regardless the increase in NF-B phosphorylation (Ser536). In fact, none of the interventions regulated NF-B target genes (Il1b and Ccl2), demonstrating low transcriptional activity. Taken together, it can be concluded that: i) adiponectin influences muscle metabolism, mainly by decreasing exercise-induced AMPK phosphorylation, inflammatory profile and IL-6 release in skeletal muscle, and ii) aerobic training attenuates progression of macrovesicular steatosis and liver inflammation through AMPK-PPAR- signaling and PPAR- activation, respectively, improving insulin resistance in obese mice. (AU)

• 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