Figure 11.Possible mechanisms of NR1D1 and PPARα modulation of hepatic lipid metabolism in aging and CR. NR1D1 and PPARα competitively bind to PPRE. Upregulation of NR1D1 during aging represses the expression of genes involved in β-oxidation, such as Cpt2, Acox1, Acaa1a, and Cyp4a1 and further induces the expression of lipogenic genes, such as Acaca, Scd1, and Fasn. These transcriptomic changes lead to hepatic lipid accumulation, which aggravates hepatic aging. However, CR may protect against the deterioration of lipid metabolism in the liver by modulating NR1D1 and PPARα.
