Proteoglycan Extracted from Ganoderma lucidum Ameliorated Diabetes-Induced Muscle Atrophy via the AMPK/SIRT1 Pathway In Vivo and In Vitro

Abstract

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.