Muscle atrophy often occurs in type 2 diabetes (T2D)
and leads
to an increase in physical disability and insulin resistance. However,
there are very few studies that have investigated potential natural
products used for this condition. In this study, we demonstrated that FYGL (Fudan-Yueyang-G. lucidum), a proteoglycan extracted from Ganoderma lucidum, ameliorated muscle atrophy in rat and mouse models of diabetes.
Histopathological analysis of muscle revealed that oral administration
of FYGL significantly prevented reduction of the
cross-sectional area of muscle fibers and overexpression of muscle
atrophic factors in diabetic rats and mice. Muscle RNA-seq analysis
in vivo indicated that FYGL regulated genes related
to myogenesis, muscle atrophy, and oxidative phosphorylation. Also, FYGL activated AMPK in vivo. Furthermore, the underlying
molecular mechanisms were studied in palmitate-induced C2C12 muscle
cells using immunofluorescence staining and Western blotting, which
revealed that FYGL inhibited muscle atrophy by stimulating
ATP production and activating the AMPK/SIRT1 pathway, thus promoting
oxidative metabolism. This result rationalized the in vivo findings.
These results suggest FYGL as a promising functional
food ingredient for the prevention of T2D-induced muscle atrophy.