phytosterols and Fatty-Liver

Increased blood cholesterol is an independent risk factor for atherosclerotic cardiovascular disease. Cholesterol homeostasis in the body is controlled mainly by endogenous synthesis, intestinal absorption, and hepatic excretion. Niemann-Pick C1-Like 1 (NPC1L1) is a polytopic transmembrane protein localized at the apical membrane of enterocytes and the canalicular membrane of hepatocytes. It functions as a sterol transporter to mediate intestinal cholesterol absorption and counter-balances hepatobiliary cholesterol excretion. NPC1L1 is the molecular target of ezetimibe, a potent cholesterol absorption inhibitor that is widely used in treating hypercholesterolemia. Recent findings suggest that NPC1L1 deficiency or ezetimibe treatment also prevents diet-induced hepatic steatosis and obesity in addition to reducing blood cholesterol. Future studies should focus on molecular mechanisms underlying NPC1L1-dependent cholesterol transport and elucidation of how a cholesterol transporter modulates the pathogenesis of metabolic diseases.

Topics: Animals; Anticholesteremic Agents; Atherosclerosis; Azetidines; Biliary Tract; Biological Transport; Carrier Proteins; Cholesterol; Endocytosis; Ezetimibe; Fatty Liver; Humans; Intestinal Absorption; Intestinal Mucosa; Intestines; Liver; Membrane Proteins; Membrane Transport Proteins; Mice; Obesity; Phytosterols; Primates

This paper reviews phytonutrients from rice bran that have shown promising disease-preventing and health-related benefits in experimental research studies. Candidate products studied and under investigation include: inositol and related compounds, inositol hexaphosphate (IP6 or phytate), rice oil, ferulic acid, gamma-oryzanol, plant sterols, tocotrienols and RICEO, a new rice-bran-derived product. Diseases in which preventive and/or nutraceutical effects have been detected include: cancer, hyperlipidemia, fatty liver, hypercalciuria, kidney stones, and heart disease. In addition, rice-bran products may have potential applications as nutritional ingredients in the context of their utility in functional foods.

Topics: Animals; Anticholesteremic Agents; Coumaric Acids; Dietary Fiber; Fatty Liver; Free Radical Scavengers; Heart Diseases; Hyperlipidemias; Inositol; Kidney Calculi; Neoplasms; Oryza; Phytosterols; Plant Extracts; Plant Oils; Rice Bran Oil; Triterpenes; Vitamin E

Intestinal failure-associated liver disease (IFALD) is a risk of parenteral nutrition (PN)-dependence. Intravenous soybean oil-based parenteral fat can exacerbate the risk of IFALD while intravenous fish oil can minimize its progression, yet the mechanisms by which soybean oil harms and fish oil protects the liver are uncertain. Properties that differentiate soybean and fish oils include α-tocopherol and phytosterol content. Soybean oil is rich in phytosterols and contains little α-tocopherol. Fish oil contains abundant α-tocopherol and little phytosterols. This study tested whether α-tocopherol confers hepatoprotective properties while phytosterols confer hepatotoxicity to intravenous fat emulsions. Utilizing emulsions formulated in the laboratory, a soybean oil emulsion (SO) failed to protect from hepatosteatosis in mice administered a PN solution enterally. An emulsion of soybean oil containing α-tocopherol (SO+AT) preserved normal hepatic architecture. A fish oil emulsion (FO) and an emulsion of fish oil containing phytosterols (FO+P) protected from steatosis in this model. Expression of hepatic acetyl CoA carboxylase (ACC) and peroxisome proliferator-activated receptor gamma (PPARγ), was increased in animals administered SO. ACC and PPARγ levels were comparable to chow-fed controls in animals receiving SO+AT, FO, and FO+P. This study suggests a hepatoprotective role for α-tocopherol in liver injury induced by the enteral administration of a parenteral nutrition solution. Phytosterols do not appear to compromise the hepatoprotective effects of fish oil.

Topics: alpha-Tocopherol; Animals; Disease Models, Animal; Fat Emulsions, Intravenous; Fatty Liver; Fish Oils; Mice, Inbred C57BL; Parenteral Nutrition; Phytosterols; Protective Agents; Soybean Oil

Pistachios contain beneficial substances such as unsaturated fatty acids, phytosterols, and polyphenols. In the present study, we investigated if pistachio consumption is able to prevent or to revert hyperglycemia, dyslipidemia, hepatic steatosis, and adipose tissue morphological alterations caused by high fat diet (HFD) in the mouse. Moreover, the impact of pistachio intake on the mRNA expression of peroxisome proliferator-activated receptor γ (

Topics: Adipose Tissue; Animals; Cholesterol; Diet; Diet, High-Fat; Dyslipidemias; Fatty Acid Synthases; Fatty Liver; Hypertriglyceridemia; Lipid Metabolism; Liver; Male; Mice, Inbred C57BL; Mice, Obese; Nuts; Obesity; Phytosterols; Pistacia; Plant Extracts; Polyphenols; PPAR gamma; RNA, Messenger; Stearoyl-CoA Desaturase; Sterol Regulatory Element Binding Protein 1

Rice bran is a by-product of rice milling and is rich in bioactive molecules such as γ-oryzanol, phytosterols, and tocotrienols. The rice bran enzymatic extract (RBEE) previously showed vessel remodeling prevention and lipid-lowering, antioxidant, anti-inflammatory, and antiapoptotic activities. The aim of this study was to identify RBEE hypolipidemic mechanisms and to study the effects of RBEE on the progression of atherosclerosis disease and linked vascular dysfunction and liver steatosis in apolipoprotein E-knockout (ApoE-/-) mice fed low- or high-fat (LFD, HFD, respectively) and cholesterol diets.. ApoE-/- mice were fed LFD (13% kcal) or HFD (42% kcal) supplemented or not supplemented with 1 or 5% RBEE (w/w) for 23 wk. Then, serum, aorta, liver, and feces were collected and flash frozen for further analysis.. RBEE supplementation of HFD improved serum values by augmenting high-density lipoprotein cholesterol and preventing total cholesterol and aspartate aminotransferase increase. 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity was attenuated (1 and 5% RBEE) and cholesterol excretion increased (5% RBEE). Diet supplementation with 5% RBEE reduced plaque development regardless of the diet. In HFD-fed mice, both doses of RBEE reduced lipid deposition and macrophage infiltration in the aortic sinus and downregulated intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression. None of these effects was observed in mice fed LFD. Liver steatosis was reduced by RBEE supplementation of LFD (1% RBEE) and HFD (1 and 5% RBEE) and nuclear peroxisome proliferator-activated receptor-α expression upregulated in the HDF 5% RBEE group.. Regular consumption of RBEE-supplemented HFD reduced plaque development and liver steatosis by decreasing inflammation and hyperlipidemia through an HMG-CoA reductase activity and lipid excretion-related mechanism.

Topics: Acyl Coenzyme A; Animals; Antioxidants; Aspartate Aminotransferases; Cholesterol, Dietary; Diet, High-Fat; Dietary Fiber; Dietary Supplements; Dose-Response Relationship, Drug; Fatty Liver; Inflammation; Intercellular Adhesion Molecule-1; Lipids; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Phenylpropionates; Phytosterols; Plant Extracts; Plaque, Atherosclerotic; PPAR alpha; Tocotrienols; Vascular Cell Adhesion Molecule-1

Certain lipid-lowering drugs increase bile lithogenicity. Here we investigated whether long-term administration of ezetimibe, a new class of hypocholesterolemic agents designed to inhibit intestinal cholesterol absorption by inhibiting Niemann-Pick C1-like 1, alters bile lithogenicity in patients with hepatobiliary diseases.. Eleven dyslipidemic patients with gallstones and/or fatty liver diseases were treated with ezetimibe (10 mg/day) for 12 months. Bile samples were collected by nasal endoscopy before and after 3 and 12 months of treatment. Serum and bile lipids and serum metabolic parameters were analyzed.. Serum levels of campesterol, total cholesterol, and low-density lipoprotein cholesterol were significantly decreased after 3 and 12 months of treatment. In contrast, serum lathosterol levels increased gradually. The lithogenic index of bile was unsaturated and unchanged in patients who were previously and concomitantly receiving ursodeoxycholic acid (UDCA). In patients who were not receiving UDCA, bile was initially supersaturated, but eventually was unsaturated. However, ezetimibe tended to elevate bile lithogenicity in cholecystectomy patients.. Long-term treatment with ezetimibe improves lipid metabolism without significantly altering the bile lithogenicity. Therefore, inhibiting intestinal cholesterol absorption in dyslipidemic patients with hepatobiliary diseases is a safe therapeutic strategy without worsening biliary physiology.

Topics: Anticholesteremic Agents; Bile; Cholesterol; Dyslipidemias; Ezetimibe; Fatty Liver; Female; Gallstones; Humans; Lipid Metabolism; Lipoproteins; Male; Middle Aged; Phytosterols; Ursodeoxycholic Acid

Various human trials and pre-clinical studies have suggested that dietary plant sterols possess hypotriacylglycerolaemic properties apart from their cholesterol-lowering properties. We hypothesised that phytosterols (PS) might attenuate triacylglycerolaemia by interfering with the deleterious effects of cholesterol overload in the liver. In the present study, twenty hamsters (Mesocricetus auratus) with diet-induced combined hyperlipidaemia were fed a high-fat diet (HFD, n 10) or a HFD supplemented with soyabean PS (n 10) for 40 d. In parallel, a healthy group was fed a standard diet (n 10). PS normalised fasting plasma cholesterol concentrations completely after 20 d and were also able to normalise serum TAG and NEFA concentrations after 40 d. HFD feeding caused microvesicular steatosis and impaired the expression of key genes related to fatty acid oxidation such as PPARA, carnitine palmitoyltransferase-Iα (CPT1A) and phosphoenolpyruvate carboxykinase 1 (PCK1) in the liver. PS treatment completely protected against HFD-induced steatosis and resulted in a normalised hepatic gene expression profile. The protection of the hepatic function by PS was paralleled by increased faecal cholesterol excretion along with a 2-fold increase in the biliary bile acid (BA):cholesterol ratio. The present study supports the conclusion that long-term consumption of PS can reduce serum TAG and NEFA concentrations and can protect against the development of fatty liver via different mechanisms, including the enhancement of BA synthesis. The results of the present study place these compounds as promising hepatoprotective agents against fatty liver and its derived pathologies.

Topics: Animals; Bile Acids and Salts; Carnitine O-Palmitoyltransferase; Cholesterol; Cricetinae; Diet, High-Fat; Dyslipidemias; Fatty Acids, Nonesterified; Fatty Liver; Gene Expression; Glycine max; Lipogenesis; Liver; Male; Mesocricetus; Non-alcoholic Fatty Liver Disease; Phosphoenolpyruvate Carboxykinase (GTP); Phytosterols; PPAR alpha; Triglycerides

ABCG5 and ABCG8 form a complex (G5G8) that opposes the absorption of plant sterols but is also expressed in liver where it promotes the excretion of cholesterol into bile. Hepatic G5G8 is transcriptionally regulated by a number of factors implicated in the development of insulin resistance and nonalcoholic fatty liver disease. Therefore, we hypothesized that G5G8 may influence the development of diet-induced obesity phenotypes independently of its role in opposing phytosterol absorption. G5G8 knock-out (KO) mice and their wild type (WT) littermates were challenged with a plant sterol-free low fat or high fat (HF) diet. Weight gain and the rise in fasting glucose were accelerated in G5G8 KO mice following HF feeding. HF-fed G5G8 KO mice had increased liver weight, hepatic lipids, and plasma alanine aminotransferase compared with WT controls. Consistent with the development of nonalcoholic fatty liver disease, macrophage infiltration, the number of TUNEL-positive cells, and the expression of proinflammatory cytokines were also increased in G5G8 KO mice. Hepatic lipid accumulation was associated with increased peroxisome proliferator activated receptor γ, CD36, and fatty acid uptake. Phosphorylation of eukaryotic translation initiation factor 2α (eiF2α) and expression of activating transcription factor 4 and tribbles 3 were elevated in HF-fed G5G8 KO mice, a pathway that links the unfolded protein response to the development of insulin resistance through inhibition of protein kinase B (Akt) phosphorylation. Phosphorylation of Akt and insulin receptor was reduced, whereas serine phosphorylation of insulin receptor substrate 1 was elevated.

Topics: Alanine Transaminase; Animals; ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; ATP-Binding Cassette Transporters; CD36 Antigens; Dietary Fats; Eukaryotic Initiation Factor-2; Fatty Liver; Insulin Receptor Substrate Proteins; Insulin Resistance; Lipoproteins; Mice; Mice, Knockout; Multiprotein Complexes; Organ Size; Phosphorylation; Phytosterols; PPAR gamma; Proto-Oncogene Proteins c-akt; Unfolded Protein Response

We investigated how liver fat content (LFC) influences cholesterol metabolism by quantifying liver fat using proton magnetic resonance spectroscopy and by measuring the serum concentrations of lathosterol, a marker of cholesterol synthesis, and sitosterol and campesterol, two markers of cholesterol absorption. We also evaluated whether this relationship could be modified by statin therapy. The study was conducted in 263 patients with type 2 diabetes, 137 of whom (52.0%) received statin therapy.. One hundred and sixty-five patients (62.7%) had steatosis (LFC>5.5%). We performed specific analyses in patients without statin therapy and in patients treated with statin therapy. In both groups, the lathosterol to cholesterol ratio correlated positively with LFC, and in multivariate analysis, the lathosterol to cholesterol ratio was associated with LFC independently of age, gender and BMI. Sitosterol and campesterol concentrations were not associated with LFC.. Our study suggests that in patients with type 2 diabetes, LFC is associated with an increase in cholesterol synthesis that is independent of obesity or diabetes mellitus. Statin therapy does not modify this relationship.

Topics: Aged; Biomarkers; Cholesterol; Diabetes Mellitus, Type 2; Dyslipidemias; Fatty Liver; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Linear Models; Liver; Magnetic Resonance Spectroscopy; Male; Middle Aged; Multivariate Analysis; Non-alcoholic Fatty Liver Disease; Phytosterols; Risk Factors; Sitosterols; Treatment Outcome

Atherosclerosis and its related complications are the leading causes of death in the West and in many developed countries. This study aims to investigate the hypolipidemic effect of bamboo shoot oil (BSO) in Sprague-Dawley rats. A group of rats had induced hyperlipidemia, hypercholesterolemia, and fatty liver by being fed with a high-fat, high-cholesterol diet for 4 wk. The control group was administered 10 mL distilled water per kg body weight, while the other groups were, respectively, administered 250 mg beta-sitosterol, 250 mg BSO, 500 mg BSO, and 1000 mg BSO per kg body weight by oral gavage. The results demonstrated that BSO could significantly decrease the levels of total cholesterol, triacylglycerol, low-density lipoprotein-cholesterol, phytosterol, lipoprotein lipase, hepatic lipase, and atherogenic index in serum, and increase the levels of cholesterol in feces. It could also significantly decrease the level of relative liver weight and liver lipids. The pronounced hypolipidemic effects of BSO might be attributed to its ability to inhibit cholesterol absorption and increase cholesterol excretion. These results suggest that consuming BSO may provide benefits in managing hypercholesterolemia. Therefore, BSO may be a good candidate for development as a functional food and nutraceutical.

Topics: Animals; Cholesterol; Diet, Atherogenic; Dose-Response Relationship, Drug; Fatty Liver; Feces; Hyperlipidemias; Hypolipidemic Agents; Lipids; Liver; Male; Organ Size; Phytosterols; Phytotherapy; Plant Oils; Plant Shoots; Poaceae; Random Allocation; Rats; Rats, Sprague-Dawley

Topics: Diet; Diet Therapy; Fatty Liver; Humans; Hypertriglyceridemia; Hypolipidemic Agents; Lipid Metabolism; Meta-Analysis as Topic; Non-alcoholic Fatty Liver Disease; Phytosterols; Risk Factors; Triglycerides