Citrus hassaku Extract Powder Increases Mitochondrial Content and Oxidative Muscle Fibers by Upregulation of PGC-1α in Skeletal Muscle

Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) is expressed in skeletal muscles and regulates systemic metabolism. Thus, nutraceuticals targeting skeletal muscle PGC-1 alpha have attracted attention to modulate systemic metabolism. As auraptene contained in citrus fruits promotes lipid metabolism and improves mitochondrial respiration, it could increase mitochondrial function through PGC-1 alpha. Therefore, we hypothesized that PGC-1 alpha is activated by auraptene and investigated its effect using Citrus hassaku extract powder (CHEP) containing >80% of auraptene. C2C12 myotubes were incubated with vehicle or CHEP for 24 h; C57BL/6J mice were fed a control diet or a 0.25% (w/w) CHEP-containing diet for 5 weeks. PGC-1 alpha protein level and mitochondrial content increased following CHEP treatment in cultured myotubes and skeletal muscles. In addition, the number of oxidative fibers increased in CHEP-fed mice. These findings suggest that CHEP-mediated PGC-1 alpha upregulation induced mitochondrial biogenesis and fiber transformation to oxidative fibers. Furthermore, as CHEP increased the expression of the protein sirtuin 3 and of phosphorylated AMP-activated protein kinase (AMPK) and the transcriptional activity of PGC-1 alpha, these molecules might be involved in CHEP-induced effects in skeletal muscles. Collectively, our findings indicate that CHEP mediates PGC-1 alpha expression in skeletal muscles and may serve as a dietary supplement to prevent metabolic disorders.

Automated summary

The study showed that Citrus hassaku extract powder can upregulate PGC-1 alpha expression in skeletal muscles, leading to increased mitochondrial biogenesis and transformation of muscle fibers into oxidative fibers. This suggests that CHEP may serve as a dietary supplement to prevent metabolic disorders.