RESUMO
The present study tested the hypothesis that acute metformin would increase peak power measured during a Wingate test. Fourteen men (24 ± 6 years; 75.8 ± 10.2 kg; 177 ± 7 cm) participated in four test sessions, conducted in a crossover, counterbalanced, double-blind model. The first and second sessions consisted of anthropometric measurements and one Wingate test per day to assess test-retest reliability. In the last two sessions, the Wingate tests were performed on metformin (500 mg capsule, 1 hour before) or placebo (cellulose capsule, 1 hour before) condition. No differences were found between the placebo and metformin for peak power (1056.8 ± 215.8 W vs. 1095.2 ± 199.3 W, respectively; p = 0.24). Mean power (630.9 ± 87.8 W vs. 613.1 ± 94.8 W, respectively; p=0.01) and total work (18928 ± 2633 kJ vs. 18393 ± 2845 kJ, respectively; p = 0.01) in the metformin condition were higher than the placebo. The power were greater in metformin when compared to the placebo in moments 3 (p = 0.01), 4 (p = 0.01), 5 (p = 0.04), 6 (p = 0.04), 7 (p = 0.02), 8 (p = 0.03) and 9 (p = 0.01) seconds. There were no differences between conditions for the peak lactate (p = 0.08) and the rating of perceived exertion (p = 0.84). Acute metformin administration increased the early power phase and the mean power of a Wingate test.
Assuntos
Teste de Esforço , Metformina , Força Muscular , Adulto , Estudos Cross-Over , Voluntários Saudáveis , Humanos , Ácido Láctico/sangue , Masculino , Metformina/administração & dosagem , Esforço Físico , Reprodutibilidade dos Testes , Adulto JovemRESUMO
Objectives: Mesenchymal Stem/Stromal Cells (MSC) are promising therapeutic tools for inflammatory diseases due to their potent immunoregulatory capacities. Their suppressive activity mainly depends on inflammatory cues that have been recently associated with changes in MSC bioenergetic status towards a glycolytic metabolism. However, the molecular mechanisms behind this metabolic reprogramming and its impact on MSC therapeutic properties have not been investigated. Methods: Human and murine-derived MSC were metabolically reprogramed using pro-inflammatory cytokines, an inhibitor of ATP synthase (oligomycin), or 2-deoxy-D-glucose (2DG). The immunosuppressive activity of these cells was tested in vitro using co-culture experiments with pro-inflammatory T cells and in vivo with the Delayed-Type Hypersensitivity (DTH) and the Graph versus Host Disease (GVHD) murine models. Results: We found that the oligomycin-mediated pro-glycolytic switch of MSC significantly enhanced their immunosuppressive properties in vitro. Conversely, glycolysis inhibition using 2DG significantly reduced MSC immunoregulatory effects. Moreover, in vivo, MSC glycolytic reprogramming significantly increased their therapeutic benefit in the DTH and GVHD mouse models. Finally, we demonstrated that the MSC glycolytic switch effect partly depends on the activation of the AMPK signaling pathway. Conclusion: Altogether, our findings show that AMPK-dependent glycolytic reprogramming of MSC using an ATP synthase inhibitor contributes to their immunosuppressive and therapeutic functions, and suggest that pro-glycolytic drugs might be used to improve MSC-based therapy.