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Chunk #19 — Results — Hepatocyte PPARα activity is context-specific

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Liver PPARα is crucial for whole-body fatty acid homeostasis and is protective against NAFLD.
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Next we evaluated the hepatic transcriptome expression pattern using microarrays. We performed hierarchical clustering (figure 3D). Most PPARα-dependent changes were observed in fasted mouse livers. Venn diagrams were used to show nutritional status-related PPARα-dependent changes (figure 3E). Among the significant DEGs, 3048 were related to fasting, 390 to ad libitum-fed animals and 156 to refed mice, suggesting context-specific PPARα activity. The results further highlighted that fasting, rather than feeding or refeeding, triggered the broader PPARα-dependent hepatocytic response, with most upregulated genes related to metabolism (figure 3E). However, the expression of several genes was identified as PPARα dependent regardless of the nutritional condition tested (fasting, but also feeding and refeeding). These genes are mostly downregulated in the absence of PPARα and pathway analysis highlights their involvement in mitochondrial fatty acid catabolism (see online supplementary file 3).