Quercetin attenuates adipogenesis and fibrosis in human skeletal muscle

Age-associated increase in ectopic fat degeneration and fibrosis in the skeletal muscle contribute to muscle degradation and weakness. Quercetin is a bioactive flavonoid with anti-inflammatory and anti-obesity effects. Thus, we aimed to investigate the effects of quercetin on adipogenesis and fibrosis in the human skeletal muscle, which have not yet been elucidated. Human muscle-derived PDGFRα⁺/CD201⁺ cells (mesenchymal progenitors) were incubated with various concentrations of quercetin (0, 0.3, 1, and 3 μM) under adipogenic or fibrogenic conditions. Lipid accumulation was visualized via Oil Red O staining. The expression of genes implicated in adipocyte or fibroblast differentiation and activation of signaling pathways was analyzed. The quercetin-treated PDGFRα⁺/CD201⁺ cells showed attenuated lipid accumulation and adipogenic gene expression (CEBPA and ADIPOQ) via the inhibition of CREB phosphorylation under adipocyte differentiation conditions. Additionally, quercetin treatment significantly attenuated the expression of fibrogenic genes (TIMP1, ACTA2, COL1A1 and COL3A1) by inhibiting Smad2 phosphorylation. Quercetin suppressed the differentiation of muscle-derived PDGFRα⁺/CD201⁺ cells to adipocytes and fibroblasts at concentrations achievable by dietary and dietary supplement intake, which indicated its preventive or therapeutic effect against the loss of muscle quality.