Figure 8. RNA-Seq showing Cpt1a^CKO kidneys with upregulated PPAR gene expression.

Bulk RNA-Seq on aged Cpt1a^fl/fl and Cpt1a^CKO kidneys and gene ontology overrepresentation analysis (ORA) were performed using enrichGO from clusterProfiler. Gene networks and pathways significantly altered between genotypes are shown (A and B), with the pathways and genes specifically related to fatty acid metabolism listed (C). Significant changes in Fabp1, a known transcriptional target of PPARα, expression, that were identified by RNA-Seq were confirmed with qPCR (n = 5–6) (D). Pdk4, another target involved in glycolysis, was significantly upregulated in aged Cpt1a^CKO murine kidneys in RNA-Seq (E) and confirmed by qPCR (n = 5–6) and protein expression (n = 3) (F and G). Scale bar: 50 μm. Primary PT cells with or without PPARα inhibitor (GW6371) had OCR responses to palmitate measured by Seahorse with a representative tracing shown (H) and quantified (I). Data are shown as the mean ± SD. *P < 0.05, **P < 0.01. Statistical significance between the 2 genotypes was determined by unpaired t test for D–F. One-way ANOVA was performed followed by Šidák’s multiple comparisons test for H.