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 hepatocyte nuclear factor 4α expression

Junko Sugatani, Tadashi Wada, Makoto Osabe, Kasumi Yamakawa, Kouichi Yoshinari, Masao Miwa

Research output: Contribution to journalArticle

56 Citations (Scopus)

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-cytochrome P450 (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 P450s in response to PB was affected by the nutritional status of the rats; mRNA levels of CYP2B1 and CYP3A1 after PB treatment, as assessed by quantitative real-time polymerase chain reaction 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 constitutive androstane receptor, pregnane X receptor, and retinoid X receptor α and coactivator peroxisome proliferator-activated receptor-γ coactivator 1α proteins was found in the hepatic nucleus between the HF and HF+I groups, but the expression of hepatocyte nuclear factor α (HNF4α) 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 HNF4α.

Original languageEnglish
Pages (from-to)1677-1687
Number of pages11
JournalDrug Metabolism and Disposition
Volume34
Issue number10
DOIs
Publication statusPublished - 2006 Sep 27

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Fingerprint Dive into the research topics of '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 hepatocyte nuclear factor 4α expression'. Together they form a unique fingerprint.

  • Cite this