Activity and mRNA levels of enzymes involved in hepatic fatty acid oxidation in mice fed citrus flavonoids

Abstract Objective We investigated the physiologic activity of citrus flavonoids, naringenin, and hesperetin in affecting the activity and mRNA levels of enzymes involved in hepatic fatty acid oxidation and serum and liver lipid levels in male ICR mice. Methods Six-week-old male ICR mice were fed experimental diets containing 1% naringenin or hesperetin and a control diet free of citrus flavonoids for 21 d. Results Naringenin caused a significant 56.1% increase in the hepatic cyanide-insensitive palmitoyl–coenzyme A oxidation rate. This compound also caused significant increases ranging from 9.8% to 55.6% in activity levels of various enzymes involved in hepatic fatty acid oxidation. These increases were accompanied by upregulation of gene expression of enzymes involved in peroxisomal fatty acid oxidation including increases of 46.8% to 88.7% of carnitine octanoyltransferase, acyl–coenzyme A oxidase, bifunctional enzyme, and 3-ketoacyl–coenzyme A thiolase. Messenger RNA levels of mitochondrial proteins involved in fatty acid oxidation except for trifunctional enzyme subunit-β were not affected by naringenin. Naringenin also significantly increased more than five-fold the mRNA level of microsomal cytochrome P-450 IV A1 involved in ω-oxidation of fatty acids. However, hesperetin did not affect any parameter of hepatic fatty acid oxidation. Naringenin, but not hesperetin, significantly lowered serum levels of triacylglycerol, cholesterol, phospholipids, and free fatty acid. Conclusion We demonstrated that naringenin has the physiologic effect of increasing hepatic fatty acid oxidation through upregulation of gene expression of enzymes involved in peroxisomal β-oxidation in mice. The change may account for the propensity of this compound to lower serum lipid levels.