PPARβ/δ Agonism with GW501516 Increases Myotube PGC-1α Content and Reduces BCAA Media Content Independent of Changes in BCAA Catabolic Enzyme Expression

Figure 10

Effect of GW501516 with and without insulin resistance on insulin sensitivity, BCAA catabolism, and extracellular BCAA accumulation. (a, b, c, and d) Effect of GW501516 (GW) at 1 μM for 24 hours both with and without GSK3787 at 10 μM both with and without insulin resistance on (a) insulin sensitivity indicated by pAkt (Ser473):Akt, (b) BCAT2, (c) BCKDHa, and (d) pBCKDHa expression. (e and f) Effect of GW with and without GSK3787 at 10 μM both with and without insulin resistance on (e) individual and cumulative extracellular BCAA normalized to nuclei content (DAPI) or (f) normalized within each independent experiment. Notes: Data were analyzed using factorial ANOVA followed by pair-wise comparisons with Bonferroni’s correction for multiple comparisons. Western blots were performed using three replicates per group across two independent experiments with each target quantified in duplicate for each sample, with for the final analysis. Media analytes were analyzed using three replicates per group across two independent experiments with each metabolite quantified in triplicate for each sample, with for the final analysis. Data with dissimilar letters indicate . When significant simple main effects for GW were not observed, exact values are displayed.

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