Effects of dietary inulin, statin, and their co-treatment on hyperlipidemia, hepatic steatosis and changes in drug-metabolizing enzymes in rats fed a high-fat and high-sucrose diet

Abstract

BackgroundRats fed a high-fat and high-sucrose (HF) diet develop hepatic steatosis and hyperlipidemia. There are several reports that a change in nutritional status affects hepatic levels of drug-metabolizing enzymes. Synthetic inulin is a dietary component that completely evades glucide digestion. Supplementing a HF diet with inulin ameliorates hypertriglycemia and hepatic steatosis, but not hypercholesterolemia. This study aimed at distinguishing the effects of synthetic inulin and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin), which inhibit cholesterol biosynthesis.MethodsWe examined effects of co-treatment with synthetic inulin (5%) and fluvastatin (0, 4, and 8 mg/kg, per os) on body weight, epidydimal white adipose tissue weight, serum and hepatic lipid profiles, and hepatic cytochrome P450 (CYP) mRNA and protein profiles in rats fed a standard diet or a HF diet for 3 weeks.ResultsTreatment with the synthetic inulin (5%) or fluvastatin at 4 mg/kg (lethal dose in rats fed the HF diet, 8 mg/kg) ameliorated the elevation in hepatic triacylglycerol and total cholesterol levels in rats fed the HF diet. Whereas co-treatment with the inulin (5%) and fluvastatin (4 mg/kg) had a tendency to more strongly suppress the elevation in serum levels of very low density lipoprotein triacylglycerol than either treatment alone, no additive or synergistic effect was found in decrease in hepatic lipid levels. Hepatic levels of CYP1A1/2 and CYP2E1 mRNA and protein and methoxyresorufin O-demethylase and ethoxyresorufin O-deethylase activities were reduced in rats fed the HF diet. The synthetic inulin alleviated the reduction in hepatic levels of CYP1A1/2 and CYP2E1 mRNA and protein more strongly than fluvastatin, and no synergistic effects were observed on co-treatment. Furthermore, hepatic levels of aryl hydrocarbon receptor mRNA were decreased in rats fed the HF diet and recovered to near normal values with the intake of dietary inulin, which correlated with change in CYP1A1/2.ConclusionsDietary inulin alone was effective to prevent the development of hepatic steatosis, ameliorate nutritional effects, and alleviate the hepatic change in the expression of CYP1A1/2 and CYP2E1, while co-treatment with statin did not have additive or synergistic effects and statin may cause adverse effects in rats fed the HF diet.

Effects of orally applied butyrate bolus on histone acetylation and cytochrome P450 enzyme activity in the liver of chicken – a randomized controlled trial

“…It is also not clear, whether under special dietary conditions or simultaneously applied with other agents, such as xenobiotics, butyrate may modify the liver enzymes of biotransformation. For example, dietary supplementation of inulin, a precursor of colonic butyrate production, in rats, suffering from high-fat-diet-induced hyperlipidaemia and hepatic steatosis, counteracted the decrease in the expression and activity of hepatic CYP1A1/2 and CYP2E1 enzymes [28]. …”

“…For instance, the HDAC inhibitor trichostatin A was shown to influence the in vitro expression of the CYP3A subfamily [27]. Alimentary added inulin, which is fermented by the colonic bacteria to SCFA, alleviates the reduction in the expression and activity of hepatic CYP1A1/2 and CYP2E1 enzymes in rats kept on a high-fat diet [28], possibly due to the epigenetic effects of the absorbed SCFA. On the basis of these findings, the enteral microbiome-produced or the orally added butyrate may also alter the activity of CYP enzymes, have an impact on hepatic detoxification capacity and drug metabolism, defined as possible pharmacoepigenetic influences.…”

Jerusalem artichoke and chungkookjang additively improve insulin secretion and sensitivity in diabetic rats

“…Fructan is a non-digestible fiber with health benefits [23-25]. It selectively stimulates the growth and/or activity of some beneficial bacteria in the colon and represses the growth of pathogens [8].…”

Effect of tetrahydrocurcumin on the profiles of drug-metabolizing enzymes induced by a high fat and high fructose diet in mice

“…An elevation in the expression of Cyp3a was also observed in a rat model of alcohol-and high fat-induced liver injury [54]. In contrast, in patients with severe stages of NAFLD, a tendency for CYP3A4 expression to decrease with the progression of NAFLD was noted [24]. In addition, CYP3A4 activity in the patients with cirrhosis was significantly reduced, whereas the levels in patients with obstructive jaundice were unchanged [55].…”

“…The concept of dietary imbalance, such as excessive consumption of high saturated fat and high fructose, has been revealed to be a contributing factor to the increased visceral adiposity and lipids associated with metabolic syndromes, which may subsequently progress into NAFLD [23,24]. Extensive studies have indicated that liver diseases cause the modifications in the expression of CYPs [25][26][27].…”