The Emerging Role of Disturbed CoQ Metabolism in Nonalcoholic Fatty Liver Disease Development and Progression

Although non-alcoholic fatty liver disease (NAFLD), characterised by the accumulation of triacylglycerol in the liver, is the most common liver disorder, the causes of its development and progression to the more serious non-alcoholic steatohepatitis (NASH) remain incompletely understood. Oxidative stress has been implicated as a key factor in both these processes, and mitochondrial dysfunction and inflammation are also believed to play a part. Coenzyme Q (CoQ) is a powerful antioxidant found in all cell membranes which has an essential role in mitochondrial respiration and also has anti-inflammatory properties. NAFLD has been shown to be associated with disturbances in plasma and liver CoQ concentrations, but the relationship between these changes and disease development and progression is not yet clear. Dietary supplementation with CoQ has been found to be hepatoprotective and to reduce oxidative stress and inflammation as well as improving mitochondrial dysfunction, suggesting that it may be beneficial in NAFLD. However, studies using animal models or patients with NAFLD have given inconclusive results. Overall, evidence is now emerging to indicate that disturbances in CoQ metabolism are involved in NAFLD development and progression to NASH, and this highlights the need for further studies with human subjects to fully clarify its role

The role of lipid and lipoprotein metabolism in non-alcoholic fatty liver disease

Due to the epidemic of obesity across the world, nonalcoholic fatty liver disease (NAFLD) has become one of the most prevalent chronic liver disorders in children and adolescents. NAFLD comprises a spectrum of fat-associated liver conditions that can result in end-stage liver disease and the need for liver transplantation. Simple steatosis, or fatty liver, occurs early in NAFLD and may progress to nonalcoholic steatohepatitis, fibrosis and cirrhosis with increased risk of hepatocellular carcinoma. The mechanism of the liver injury in NAFLD is currently thought to be a multiple-hit process where the first hit is an increase in liver fat, followed by multiple additional factors that trigger the inflammatory activity. At the onset of disease, NAFLD is characterized by hepatic triglyceride accumulation and insulin resistance. Liver fat accumulation is associated with increased lipotoxicity from high levels of free fatty acids, free cholesterol and other lipid metabolites. As a consequence, mitochondrial dysfunction with oxidative stress and production of reactive oxygen species and endoplasmic reticulum stress-associated mechanisms, are activated. The present review focuses on the relationship between intra-cellular lipid accumulation and insulin resistance, as well as on lipid and lipoprotein metabolism in NAFLD

Lipoprotein(a) Lowering-From Lipoprotein Apheresis to Antisense Oligonucleotide Approach

It is well-known that elevated lipoprotein(a)-Lp(a)-levels are associated with a higher risk of cardiovascular (CV) mortality and all-cause mortality, although a standard pharmacotherapeutic approach is still undefined for patients with high CV risk dependent on hyperlipoproteinemia(a). Combined with high Lp(a) levels, familial hypercholesterolemia (FH) leads to a greater CVD risk. In suspected FH patients, the proportion of cases explained by a rise of Lp(a) levels ranges between 5% and 20%. In the absence of a specific pharmacological approach able to lower Lp(a) to the extent required to achieve CV benefits, the most effective strategy today is lipoprotein apheresis (LA). Although limited, a clear effect on Lp(a) is exerted by PCSK9 antagonists, with apparently different mechanisms when given with statins (raised catabolism) or as monotherapy (reduced production). In the era of RNA-based therapies, a new dawn is represented by the use of antisense oligonucleotides APO(a)Lrx, able to reduce Lp(a) from 35% to over 80%, with generally modest injection site reactions. The improved knowledge of Lp(a) atherogenicity and possible prevention will be of benefit for patients with residual CV risk remaining after the most effective available lipid-lowering agents

Assessment of Apolipoprotein(a) Isoform Size Using Phenotypic and Genotypic Methods

Apolipoprotein(a) (apo(a)) is the protein component that defines lipoprotein(a) (Lp(a)) particles and is encoded by the LPA gene. The apo(a) is extremely heterogeneous in size due to the copy number variations in the kringle-IV type 2 (KIV2) domains. In this review, we aim to discuss the role of genetics in establishing Lp(a) as a risk factor for coronary heart disease (CHD) by examining a series of molecular biology techniques aimed at identifying the best strategy for a possible application in clinical research and practice, according to the current gold standard

Coenzyme Q10 and Cardiovascular Diseases

Coenzyme Q10 (CoQ10), which plays a key role in the electron transport chain by providing an adequate, efficient supply of energy, has another relevant function as an antioxidant, acting in mitochondria, other cell compartments, and plasma lipoproteins. CoQ10 deficiency is present in chronic and age-related diseases. In particular, in cardiovascular diseases (CVDs), there is a reduced bioavailability of CoQ10 since statins, one of the most common lipid-lowering drugs, inhibit the common pathway shared by CoQ10 endogenous biosynthesis and cholesterol biosynthesis. Different clinical trials have analyzed the effect of CoQ10 supplementation as a treatment to ameliorate these deficiencies in the context of CVDs. In this review, we focus on recent advances in CoQ10 supplementation and the clinical implications in the reduction of cardiovascular risk factors (such as lipid and lipoprotein levels, blood pressure, or endothelial function) as well as in a therapeutic approach for the reduction of the clinical complications of CVD

RELATIONSHIP BETWEEN WAIST-HIP RATIO (WHR) AND TOTAL CHOLESTEROL LEVELS OF EMPLOYEES IN STIKES BINA SEHAT PPNI

Introduction: Waist-Hip Ratio (WHR) is an anthropometric indicator which accurate enough to describe the composition of body fat associated with central obesity. Waist circumference illustrates the high deposits of dangerous fat in the body, while the hip circumference is a protective factor in cardiovascular disease events. Method: This research was used correlation analysis with cross sectional approach. There were two research variables, WHR as independent variable and total cholesterol levels as dependent variable. Population this study were all employees of STIKES Bina Sehat PPNI Mojokerto, 79 respondents. Sampling technique used in this study was purposive sampling. The sample of this study were all employees of STIKES Bina Sehat PPNI Mojokerto who are accordance with the inclusion criteria as many as 35 people. Data were collected using meter line to measure waist-hip circumference and use cholesterol test kit to measure total cholesterol levels. Result: The results of Spearman Rho Test showed there was no correlation between WHR and total cholesterol levels, p = 0,688 ( p > 0,05 ) and r = 0.06. Conclusion: This result research showed there was no significant correlation between WHR and total cholesterol levels of employees in STIKES Bina Sehat PPNI Mojokerto. So that, not all people who have excessive WHR will have excessive total cholesterol levels too. Keywords: Antropometri, Waist Hip Ratio, Total Cholestero

Challenges and opportunities on lipid metabolism disorders diagnosis and therapy: Novel insights and future perspective

Dyslipidemia has been globally recognized, for almost seven decades, as one of the most important risk factors for the development and complications of atherosclerotic cardiovascular disease (ASCVD) [...]

Decreased VLDL-Apo B 100 fractional synthesis rate despite hypertriglyceridemia in subjects with type 2 diabetes and nephropathy

Subjects with Type 2 Diabetes Mellitus (T2DM) and diabetic nephropathy (DN) often exhibit hypertriglyceridemia. The mechanism(s) of such an increase are poorly known. OBJECTIVE: We investigated VLDL-Apo B 100 kinetics in T2DM subjects with and without DN, and in healthy controls. DESIGN: Stable isotope 13C-leucine infusion, and modelling analysis of tracer-to-tracee ratio dynamics in the protein product pool in the 6-8 hr period following tracer infusion, were employed. SETTING: Male subjects affected by T2DM, either with (n=9) or without (n=5) DN, and healthy male controls (n=6), were studied under spontaneous glycemic levels in the post-absorptive state. RESULTS: In the T2DM patients with DN, plasma triglyceride (TG) (2.2\ub10.8 mmol/L, Mean\ub1SD) and VLDL-Apo B 100 (17.4\ub110.4 mg/dl) concentrations, and VLDL-Apo B 100 pool (0.56\ub10.29 g), were 3e60-80% greater (p<0.05 or less) than those of the T2DM subjects without DN (TG: 1.4\ub10.5 mmol/L; VLDL-Apo B 100: 9.9\ub12.5 mg/dl; VLDL-Apo B 100 pool: 0.36\ub10.09 g), and 3e80-110% greater (p<0.04 or less) than those of nondiabetic controls (TG: 1.2\ub10.4 mmol/L; VLDL-Apo B 100: 8.2\ub11.7 mg/dl; VLDL-Apo B 100: 0.32\ub10.09 g). In sharp contrast however, in the subjects with T2DM and DN, VLDL-Apo B 100 FSR was 6550% lower (4.8\ub12.2 pools/day) than that of either the T2DM subjects without DN (9.9\ub14.3 pools/day, p<0.025) or the control subjects (12.5\ub19.1 pools/day, p<0.04). CONCLUSIONS: The hypertriglyceridemia of T2DM patients with DN is not due to hepatic VLDL-Apo B 100 overproduction, which is decreased, but it should be attributed to decreased apolipoprotein removal

Comparison of the neuroprotective effects of aspirin, atorvastatin, captopril and metformin in diabetes mellitus

Objective: The aim of this study was to investigate the effect of combined intake of a high dose of aspirin, atorvastatin, captopril and metformin on oxidative stress in the brain cortex and hippocampus of streptozotocin (STZ)-induced diabetic rats. Material and methods: Rats were randomly divided into the following 11 groups: control and diabetic (D), as well as 9 groups that were treated with metformin (M, 300 mg/kg) or aspirin (ASA, 120 mg/kg) alone or in different combinations with captopril (C, 50 mg/kg) and/or atorvastatin (AT, 40 mg/kg) as follows: (D + M), (D + ASA), (D + M + ASA), (D + M + C), (D + M + AT), (D + M + C + ASA), (D + M + C + AT), (D + M + AT + ASA) and (D + M + C + AT + ASA). The rats in treatment groups received drugs by gavage daily for six weeks. Serum lipid profile and levels of oxidative markers in the brain cortex and hippocampus tissues were evaluated. Results: The levels of malondialdehyde in the brain cortex and hippocampus in all the treated groups decreased significantly (p < 0.05). There was a significant increase in the total thiol concentration as well as catalase activity in treated rats in (M + AT), (M + C + ASA), (M + C + AT), (M + AT + ASA) and (M + C + AT + ASA) groups in cortex and hippocampus in comparison with the diabetic rats (p < 0.05). Also, the superoxide dismutase activity in all treated rats with medications was significantly increased compared to the diabetic rats (p < 0.05–0.01). Conclusion: Our findings showed that the combined use of high-dose aspirin, metformin, captopril and atorvastatin potentiated their antioxidant effects on the brain, and hence could potentially improve cognitive function with their neuroprotective effects on hippocampus