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 4alpha expression.
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 alpha and coactivator peroxisome proliferator-activated receptor-gamma coactivator 1alpha proteins was found in the hepatic nucleus between the HF and HF+I groups, but the expression of hepatocyte nuclear factor alpha (HNF4alpha) 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 HNF4alpha.
Sugatani
Junko
J
Department of Pharmaco-Biochemistry and COE21, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka City, Shizuoka 422-8526, Japan.
Wada
Tadashi
T
Osabe
Makoto
M
Yamakawa
Kasumi
K
Yoshinari
Kouichi
K
Miwa
Masao
M
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D000090702:Constitutive Androstane Receptor; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D003907:Dexamethasone / Q000008:administration & dosage / Q000633:toxicity; D004041:Dietary Fats / Q000008:administration & dosage / Q000633:toxicity; D019422:Dietary Sucrose / Q000008:administration & dosage / Q000633:toxicity; D005234:Fatty Liver / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D015870:Gene Expression / Q000187:drug effects; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics* / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015151:Immunoblotting; D007444:Inulin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D047493:PPAR alpha / Q000378:metabolism; D010634:Phenobarbital / Q000008:administration & dosage / Q000633:toxicity; D000077297:Pregnane X Receptor; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism; D047488:Retinoid X Receptors / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015262:Xenobiotics / Q000008:administration & dosage / Q000633:toxicity*
D000090702:Constitutive Androstane Receptor; D004041:Dietary Fats; D019422:Dietary Sucrose; D051557:Hepatocyte Nuclear Factor 4; D047493:PPAR alpha; D000077297:Pregnane X Receptor; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D015262:Xenobiotics; D003907:Dexamethasone; D007444:Inulin; D003577:Cytochrome P-450 Enzyme System; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D010634:Phenobarbital