Dietary oleanolic acid mediates circadian clock gene expression in liver independently of diet and animal model but requires apolipoprotein A1

Oleanolic acid is present in virgin olive oil at a concentration of 57 mg/kg.

• Long-term administration of oleanolic acid in Apoe-deficient mice increased the hepatic area occupied by lipid droplets without altering oxidative stress.
• Significant increases in the expression of Bmal1, Clock, Elovl3, Tubb2a, and Cldn1 were observed, while Amy2a5, Usp2, Per3, and Thrsp expressions significantly decreased.
• Bmal1 and Cldn1 expression levels were positively associated with the presence of lipid droplets in the liver.
• Increased expressions of Clock and Bmal1 were also noted in rats but not in Apoa1-deficient mice.
• Oleanolic acid appears to target core liver clock components independently of the diets provided, requiring APOA1-containing high-density lipoproteins for its hepatic effect.

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