Figure 4

PPARα binds extensively near genes involved in gluconeogenesis/glycolysis in CR and HFD livers and activation by fenofibrate enhances anaerobic glycolysis in primary hepatocytes. (A) Canonical gluconeogenesis/glycolysis pathway highlighting genes bound by PPARα (purple outline boxes) and genes both bound by PPARα in our dataset and sensitive to fibrate in Kane et al.²⁰ (blue outline boxes). The two-element color bars near the bound genes represent the log₂ fold-changes in mRNA expression (by RNA-Seq) for these genes in HFD and CR livers, respectively, versus CD. *Indicates statistically significant changes (q < 0.05). (B) Lactate production in mouse primary hepatocytes following vehicle (black line) or fenofibrate (red line) treatment in the presence of glucose. (C) Glucose production in the presence of lactate/pyruvate as a gluconeogenic source following vehicle (black line) or fenofibrate (red line) treatment. (D) Oxygen consumption rate (OCR) assessed in the presence of glucose following vehicle (black line) or fenofibrate (red line) treatment. OCR also assessed following oligomycin, FCCP, and rotenone drug treatments. (E–G) Assessment of basal OCR (E), respiratory capacity (F), and ATP turnover (G) in primary hepatocytes following vehicle or fenofibrate treatment.