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. 2022 Sep 11;65:101598. doi: 10.1016/j.molmet.2022.101598

Figure 7.

Figure 7

MSDC-0602K decreases adipocyte differentiation in hBM-MSC and differently changes cellular metabolism compared to classical TZDs. hBM-MSCs were treated for 10 days with 1 μM and 10 μM concentrations of different TZDs (rosiglitazone-ROSI, pioglitazone-PIO) or TZD analog (MSDC-0602K) together with differentiation cocktail for OB and AD differentiation. Vehicle (DMSO) was used as a control (A) OB differentiation of hBM-MSCs: gene expression of ALPL, MPC1, MPC2 following OB differentiation (D10) in treatment with 1uM PIO, ROSI and MSDC and vehicle (DMSO) as a control; (B) AD differentiation of hBM-MSCs: quantification of Nile Red staining of mature adipocytes normalized to cell viability following AD differentiation in treatment with 1 μM PIO, ROSI and MSDC and vehicle (DMSO) as a control; Data are presented as mean ± SEM from two independent experiments. One-way ANOVA, Tukey's multiple comparison test, a: Vehicle vs other groups; b: PIO vs other groups. (C-D) hBM-MSCs were acutely treated with 30 μM concentration of different TZDs (rosiglitazone-ROSI, pioglitazone-PIO) and TZD analog (MSDC-0602), and MPC inhibitor (UK5099) and their effect on mitochondrial respiration was analyzed. (C-D) Changes in oxygen consumption rate (OCR) of hBM-MSCs in response to treatment with TZDs, TZD analog and UK5099 and corresponding calculations of basal respiration, maximal respiration and spare capacity; Data are presented as mean ± SEM from at least two independent experiments with five replicates per condition; one-way ANOVA, Tukey's multiple comparison test, a: Veh vs other groups; b: PIO vs other groups, c: ROSI vs other groups, d: MSDC vs other groups. (E) Measurement of glucose uptake in hBM-MSC cells after 1.5-hour incubation with 1 μM INS, 30 μM PIO/ROSI/MSDC and 2 μM UK5099. Data are presented as the fold change of normalized relative light unit (RLU) value/protein of stimulated cells over non-stimulated cells. Data are presented as mean ± SEM (n = 7–11 per group); ordinary one-way ANOVA, Tukey's multiple comparison test, a: INS vs other groups; b: PIO vs other groups. Measurement of intracellular glutamate (F) and glutamine (G) in hBM-MSC cells after 3 h incubation with 1 μM INS, 30 μM PIO/MSDC and 2 μM UK5099. Data are presented as the fold change of normalized RLU value/protein of stimulated cells over non-stimulated cells. Data are presented as mean ± SEM (n = 7–11 per group); ordinary one-way ANOVA, Tukey's multiple comparison test, a: ND vs other groups.