Fig. 6

Cisd2-dependent and Cisd2-independent DEGs in the skeletal muscles of WT and Cisd2 mcKO mice after hesperetin treatment for 4 months. A The 3-month old WT and Cisd2 mcKO mice, which carry a Cisd2KO background specifically in the skeletal and cardiac muscles, were treated with dietary hesperetin (Hes) (100 mg/kg/day provided in food) or Veh control food (3.04% propylene glycol, w/w) for 4 months and sacrificed at 7-month old. The transcriptome of skeletal. muscle (gastrocnemius) were analyzed for the following four groups of mice: WT-hesperetin, WT-Veh, Cisd2 mcKO-hesperetin and Cisd2 mcKO-Veh. B Principal component analysis (PCA, EZinfo 3.0.3 software) of all the genes affected by hesperetin in the skeletal muscle of WT mice (91 DEGs, WT-hesperetin vs WT-Veh, FDR < 0.2). C Heatmap illustrating that the 91 DEGs (62 up-regulated and 29 down-regulated genes) can be divided into two groups: Cisd2-dependent (72/91; 79%) and Cisd2-independent (19/91; 21%). Cisd2-dependent DEGs: mcKO-hesperetin vs mcKO-Veh; p > 0.05. Cisd2-independent DEGs: mcKO-hesperetin vs mcKO-Veh; p < 0.05. D Pathway analysis of the Cisd2-dependent DEGs. Metabolism, which is the number one pathway, is sub-divided into four pathways, namely protein metabolism, nitrogen metabolism, nucleotide and nucleic acid metabolism, and lipid metabolism. E Pathway analysis of the Cisd2-independent DEGs. Metabolism, which is again the main pathway affected by hesperetin, is sub-divided into three pathways, namely nitrogen metabolism, nucleotide and nucleic acid metabolism, and lipid metabolism. The grouping of the pathways was carried out by MGI GO term finder (pathway p < 0.05)