Received for publication April 17, 2006.
Revised June 24, 2006.
Accepted for publication June 27, 2006.

Dietary inulin alleviates hepatic steatosis and xenobiotics-induced liver injury in rats fed a high-fat and high-sucrose diet: Association with the suppression of hepatic cytochrome P450 and HNF4 expression

Abstract

Inulin enzymatically synthesized from sucrose is a dietary component that completely escapes glucide digestion. Supplementing inulin to a high-fat and high-sucrose diet (HF) ameliorated hypertriglycemia and hepatic steatosis in 8-week-fed rats by suppressing elevated levels of serum triacylglycerols, fatty acids and glucose, and the accumulation of hepatic triacylglycerols and fatty acids. Inulin intake prevented phenobarbital (PB)- and dexamethasone-induced liver injuries in the HF group. No significant alteration in the baseline expression of CYP2B, CYP2C11, CYP3A and NADPH P450 reductase mRNAs and proteins was found. In contrast, baseline and PB-treated expressions of CYP2E1 mRNA were reduced in HF-fed rats. The induction of CYPs in response to PB was affected by their nutritional status; mRNA levels of CYP2B1 and CYP3A1 after PB treatment as assessed by quantitative real-time PCR analysis were reduced in the inulin-supplemented HF (HF+I) group, compared with those in the HF group. Western-blot analysis detected the corresponding changes of CYP2B and CYP3A proteins. These alterations were correlated with changes in hepatic thiobarbituric acid-reactive substances. Furthermore, no significant difference in the expression of nuclear receptors CAR, PXR, and RXR and coactivator PGC1 proteins was found in the hepatic nucleus between HF and HF+I groups, but the expression of HNF4 protein was significantly reduced in the HF+I group. Taken together, these results indicate that inulin intake ameliorates PB-induced liver injury, associated with a decline in lipid accumulation and PB-induced expression of CYP2B and CYP3A, which may be related by a reduction in the nuclear expression of HNF4.

Key words: CAR, CYP expression, CYP gene regulation, CYP induction, CYP2B, CYP3A, drug-induced hepatotoxicity, enzyme induction, nuclear receptors

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