Young apple polyphenols improve skeletal muscle function via modulating mitochondrial homeostasis in diabetic mice

A dual-phase approach was employed: (1) Population-based metabolic profiling comparing diabetic individuals with normal versus impaired muscle function; (2) Preclinical validation using diabetic murine models subjected to a 12-week YAPs intervention. Post-intervention analyses included quantification of gastrocnemius muscle myosin isoform dynamics, mitochondrial functional biomarkers, AMPK pathway activation, and tricarboxylic acid (TCA) cycle metabolites to delineate mechanistic links between YAPs and metabolic restoration.ResultsIn diabetic patients, impaired muscle strength correlated with disrupted TCA cycle metabolites (isocitrate, α-ketoglutarate).

In mice, compared to the control group, the experimental group mice showed a significant decrease in fasting blood glucose, serum insulin, and HOMA-IR index, along with a noticeable increase in grip strength. YAPs improved skeletal muscle function in diabetic mice by promoting the expression of Myosin Heavy Chain 7 and Myosin Heavy Chain 2a, and lowers the expression of Fbxo32 and Myostatin. Furthermore, YAPs improved mitochondrial function, as evidenced by increased ATP (Adenosine triphosphate) contents, mtDNA copy number, enzyme activity of SDH (Succinate dehydrogenase) and MDH (Malate dehydrogenase), and the expression of SDHB (Succinate dehydrogenase complex iron sulfur subunit B) and Complex II (Mitochondrial respiratory chain complex II).

Meanwhile, YAPs reduced succinate and malate concentrations in the gastrocnemius muscle of diabetic mice.ConclusionsThe decline in muscle function associated with diabetes is related to the TCA cycle. Supplementation of YAPs improved skeletal muscle function in diabetic mice by regulating mitochondrial function.