Fig. 4.

Pharmacological treatment with the PPAR agonist bezafibrate and the CPT1 inhibitor etomoxir followed by palmitate loading. Representative acylcarnitine products of short- (C4:0), medium- (C8:0), and long-chain (C16:0) species are depicted. Three independent experiments were performed in triplicates each. Results are presented as mean ± SEM. Statistically significant differences of pharmacological treatments relative to the untreated control are indicated by an asterisk (P < 0.05). For each metabolite, values not sharing a common letter indicate statistically significant differences in metabolite abundance between concentrations (P < 0.05). A: Stimulation of FA β-oxidation following pretreatment with the PPAR agonist bezafibrate and subsequent palmitate loading (100 µM, 120 min). Bezafibrate was dissolved in DMSO; the final concentration of DMSO per well was 0.05%. Primary human fibroblasts (10⁵ cells/well) were incubated with increasing bezafibrate concentrations (10, 30, 100, 300 µM) for 48 h (38) in DMEM (1 g/l glucose) and 0.25% FA-free BSA. Results are expressed as fold increase in metabolite abundance compared with the untreated control (0.05% DMSO). B: Inhibition of FA β-oxidation following pretreatment with the CPT1 inhibitor etomoxir and subsequent palmitate loading (100 µM, 120 min). Etomoxir was dissolved in H₂O. Prior to permeabilization, fibroblasts (10⁵ cells/well) were pretreated with different etomoxir concentrations (10, 20, 50, 100 µM) for 30 min (42) in DMEM (1 g/l glucose) and 0.25% FA-free BSA. Results are expressed as fold decrease in metabolite abundance compared with the untreated control (H₂O; indicated by the dotted line).