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. 2021 Dec 2;12:7031. doi: 10.1038/s41467-021-27133-7

Fig. 5. PPARα antagonism reduces fatty acid uptake and villi length in human intestinal biopsies.

Fig. 5

a Graphical representation of the human epithelial biopsy culture. b, c Basolateral (b) and apical radioactivity (c) of dipeptide [3H]GlySar, n = 7 per group of epithelial biopsy insets cultured seven days with PPARα antagonist 5 μM GW-6471 or DMSO. d, e Apical concentration of free fatty acids (d) and calculated palmitate absorption between 2 and 4 h, n = 7 (vehicle), 6 (GW-6471) biopsy insets (e). f Trans-epithelial electrical resistance at the end of the experiment, n = 7 (vehicle), six (GW-6471) biopsy insets. g, h Full villi lengths n = 88 (vehicle), 63 (GW-6471), pooled from n = 5 (vehicle), four (GW-6471) biopsy insets after nine days of treatment (g) and representative H&E staining with villi tracing (h). i, j Full villi lengths after nine days of incubation with PPARα antagonist 5 μM NXT-629 (n = 70 villi), or vehicle (n = 38 villi), pooled from four cell culture insets per group (i) and representative H&E staining of villi (j). k Palmitate absorption in 4 h, from n = 6 (vehicle) and four (NXT-629) insets per group, calculated from apical FFA concentration measurements. l Graphical representation of the mechanism of pharmacological PPARα agonism (Wy-14643) and antagonism (GW-6471), and of the fatty acid oxidation inhibitor etomoxir. m Fatty acid oxidation in human epithelial samples measured by scintillation counting of [14C]CO2 that is released by in vitro β-oxidation of [14C]-palmitate, n = 2 (DMSO, etomoxir), three (Wy-14643, Wy-14643+etomoxir). np Basolateral radioactivity of dipeptide [3H]GlySar after 4 h of transport (n), palmitate absorption in 4 h, calculated from apical FFA measurements (o) and relative qPCR gene expression in epithelial biopsies, normalized to Tbp (p) after 10-day inhibition with DMSO, 4 μM Wy-14643, 50 μM etomoxir, and Wy-14643 + etomoxir, n = 6 biopsy insets per group. q Relative qPCR gene expression after GW-6471 treatment, n = 7 (vehicle), eight (GW-6471) insets per group. bh and q are pools from two independent experiments. All data represent mean ± S.D, *P ≤ 0.05, **P < 0.01, ***P < 0.001 of t-test confidence level 95%. Source data are provided as a Source Data file.