coenzyme-q10 and Non-alcoholic-Fatty-Liver-Disease

Non-alcoholic fatty liver disease (NAFLD) is a clinical condition characterized by lipid infiltration of the liver, highly prevalent in the general population affecting 25% of adults, with a doubled prevalence in diabetic and obese patients. Almost 1/3 of NAFLD evolves in Non-Alcoholic SteatoHepatitis (NASH), and this can lead to fibrosis and cirrhosis of the liver. However, the main causes of mortality of patients with NAFLD are cardiovascular diseases. At present, there are no specific drugs approved on the market for the treatment of NAFLD, and the treatment is essentially based on optimization of lifestyle. However, some nutraceuticals could contribute to the improvement of lipid infiltration of the liver and of the related anthropometric, haemodynamic, and/or biochemical parameters. The aim of this paper is to review the available clinical data on the effect of nutraceuticals on NAFLD and NAFLD-related parameters. Relatively few nutraceutical molecules have been adequately studied for their effects on NAFLD. Among these, we have analysed in detail the effects of silymarin, vitamin E, vitamin D, polyunsaturated fatty acids of the omega-3 series, astaxanthin, coenzyme Q10, berberine, curcumin, resveratrol, extracts of

Topics: Antioxidants; Berberine; Curcumin; Dietary Supplements; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Humans; Meta-Analysis as Topic; Non-alcoholic Fatty Liver Disease; Obesity; Observational Studies as Topic; Plant Extracts; Probiotics; Randomized Controlled Trials as Topic; Resveratrol; Salvia miltiorrhiza; Silymarin; Ubiquinone; Vitamin D; Vitamin E; Xanthophylls

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver injury. Chronic exposure to oxidative stress leads to depletion of liver antioxidants and abnormal cytokine production; antioxidant therapy is one of the main therapeutic lines in NAFLD. In the current study we aimed to investigate the effect of coenzyme Q10 (coQ10) therapy on several adipocytokines and insulin resistance in patients with NAFLD.. In the current randomized double-blind placebo controlled trial 44 NAFLD patients were enrolled. After randomization into two groups, 22 patients received 100 mg/day coQ10 capsules and 22 patients received placebo daily for 4 weeks. BMI and WHR were calculated for patients at the beginning and end of the study and blood samples were obtained from the patients to measure serum concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), fasting serum glucose (FSG), insulin resistance (IR), vaspin, chemerin, pentraxin 3 (PTX3) and markers of oxidative stress including total antioxidant capacity (TAC) and malondialdehyde (MDA).. After 4 weeks of coQ10 supplementation, waist circumference (WC) and serum AST and TAC concentrations significantly decreased in intervention group (p <0.05) but no significant changes occurred in placebo-treated group. In stepwise multivariate linear regression model, change in serum FSG was a significant predictor of changes in serum vaspin, chemerin and pentraxin 3 (p <0.001).. The present study showed a potential for coQ10 therapy in improving several anthropometric and biochemical variables in NAFLD. Longer studies with higher doses of coQ10 are required to further evaluate this potential benefit.

Topics: Adipokines; Adult; Alanine Transaminase; Antioxidants; Aspartate Aminotransferases; Biomarkers; Blood Glucose; C-Reactive Protein; Chemokines; Dietary Supplements; Double-Blind Method; Female; Humans; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Oxidative Stress; Serpins; Serum Amyloid P-Component; Ubiquinone; Waist Circumference; Young Adult

Topics: Ascorbic Acid; Diet, Reducing; Humans; Lipids; Liver; Non-alcoholic Fatty Liver Disease; Obesity; Selenomethionine; Silymarin; Ubiquinone; Vitamin E

Coenzyme Q10 (CoQ10) is a well-known anti-adipogenic factor that possesses the capability to regulate non-alcoholic fatty liver disease (NAFLD). However, the mechanism by which CoQ10 acts on NAFLD is still unclear. In this study, the role of CoQ10 in the prevention of NAFLD was investigated in vivo and in vitro. C57BL/6J mice were fed a normal diet, high-fat diet (HFD) or HFD supplemented with CoQ10 (1800 mg kg-1 HFD) for 24 weeks. HepG2 cells were treated with sodium palmitate for investigating the mechanism of action of CoQ10 on NAFLD. The results showed that CoQ10 alleviated HFD-induced weight gain and NAFLD, accompanied by an anti-hyperlipidaemia effect, by reducing the serum triglycerides, total cholesterol, and low-density lipoprotein cholesterol levels. Importantly, CoQ10 could downregulate the expression of sterol regulatory element-binding protein-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS), which are related to lipid synthesis, and upregulate the expression of peroxisome proliferator-activated receptors α (PPARα) and carnitine palmitoyltransferase-1 (CPT-1) associated with fatty acid oxidation. Similar to the results from mice, treatment with CoQ10 alleviated sodium palmitate-induced hepatocyte steatosis via the inhibition of lipogenesis and promotion of fatty acid oxidation. However, Compound C, as an AMPK inhibitor, could significantly block the benefits derived from CoQ10 treatment. In conclusion, CoQ10 could serve as an AMPK activator and regulate the hepatic lipid metabolism to inhibit the abnormal accumulation of hepatic lipids and prevent NAFLD progression.

Topics: AMP-Activated Protein Kinases; Animals; Cell Proliferation; Diet, High-Fat; Gene Expression Regulation; Hep G2 Cells; Humans; Lipid Peroxidation; Lipids; Male; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Ubiquinone

Current peroxisome proliferator-activated receptor (PPAR)-targeted drugs, such as the PPARγ-directed diabetes drug rosiglitazone, are associated with undesirable side effects due to robust agonist activity in non-target tissues. To find new PPAR ligands with fewer toxic effects, we generated transgenic zebrafish that can be screened in high throughput for new tissue-selective PPAR partial agonists. A structural analog of coenzyme Q

Topics: 3T3-L1 Cells; Animals; Animals, Genetically Modified; Benzoquinones; Drug Evaluation, Preclinical; HEK293 Cells; Humans; Ligands; Lipid Metabolism; Liver; Male; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; PPAR alpha; PPAR gamma; Ubiquinone; Zebrafish

Topics: Alanine Transaminase; Alkaline Phosphatase; Ammonia; Animals; Aspartate Aminotransferases; Bilirubin; Biomarkers; Brain-Derived Neurotrophic Factor; Choline; Choline Deficiency; Diet; Dose-Response Relationship, Drug; gamma-Glutamyltransferase; Interleukin-6; Liver; Male; Methionine; Neuroprotective Agents; Nitric Oxide; Non-alcoholic Fatty Liver Disease; Rats; Rats, Wistar; Serum Albumin; Ubiquinone

Oxidative stress is believed to be a major contributory factor in the development of non alcoholic fatty liver disease (NAFLD), the most common liver disorder worldwide. In this study, the effects of high fat diet-induced NAFLD on Coenzyme Q (CoQ) metabolism and plasma oxidative stress markers in rats were investigated. Rats were fed a standard low fat diet (control) or a high fat diet (57% metabolizable energy as fat) for 18 weeks. The concentrations of total (reduced + oxidized) CoQ9 were increased by >2 fold in the plasma of animals fed the high fat diet, while those of total CoQ10 were unchanged. Reduced CoQ levels were raised, but oxidized CoQ levels were not, thus the proportion in the reduced form was increased by about 75%. A higher percentage of plasma CoQ9 as compared to CoQ10 was in the reduced form in both control and high fat fed rats. Plasma protein thiol (SH) levels were decreased in the high fat-fed rats as compared to the control group, but concentrations of lipid hydroperoxides and low density lipoprotein (LDL) conjugated dienes were unchanged. These results indicate that high fat diet-induced NAFLD in rats is associated with altered CoQ metabolism and increased protein, but not lipid, oxidative stress.

Topics: Animals; Dietary Fats; Lipoproteins, LDL; Male; Non-alcoholic Fatty Liver Disease; Oxidation-Reduction; Oxidative Stress; Rats; Rats, Wistar; Sulfhydryl Compounds; Ubiquinone