Figure 5.

MSDC-0602K increases glycolytic activity along with decreased senescence of mBM-MSCs in comparison to pioglitazone in obese mice. (A) Glycolysis, glycolytic capacity and glycolytic reserve measured from extracellular acidification rate (ECAR) of mBM-MSCs (n = 2 independent experiments with five replicates per group). (B) Basal respiration, maximal respiration and spare capacity measured from oxygen consumption rate (OCR) of primary mBM-MSCs isolated from treated mice with different dietary interventions (n = 2 independent experiments with five replicates per group). Data are presented as mean ± SEM (n = 7–11 per group), one-way ANOVA, Tukey's multiple comparison test, a: ND vs other groups, b: HFD vs other groups, c: HFD + P vs other groups, d: HFD + M vs other groups. (C) ROS production (%) of cultivated primary mBM-MSCs isolated after 8 weeks on HFD or HFD supplemented with TZD and TZD analog. (D) Expression of genes associated with cell senescence (Sod2, Hmox1, p53, p16, Vcam, Tnfα) measured in differentiated mBM-MSCs (n = 2 per group from pooled samples). (E) Gene expression of SASP markers in primary mBM-MSCs obtained from treated mice exposed to 50uM H₂O₂ for 6h (Fas, Fasgl, Il1b, Vegfa, Il10, Il1rn) (n = 2 per group from pooled samples); (F) Gene expression profile of basic mitochondrial genes such as Pdk4, Pc, Mpc1 and Mpc2 in mBM-MSC differentiated towards osteoblasts. Data are presented as mean fold change (F.C.) of gene expression normalized to ND group ± SEM (n = 2 per group from pooled samples); one-way ANOVA, Tukey's multiple comparison test, a: ND vs other groups, b: HFD vs other groups, c: HFD + P vs other groups, d: HFD + M vs other groups.