The effect of rosuvastatin alone or in combination with fenofibrate or omega-3 fatty acids on lipoprotein(a) levels in patients with mixed hyperlipidemia.

Introduction: Lipoprotein(a) [Lp(a)] is a strong, genetically determined, pathogenetic factor of atherosclerotic cardiovascular disease (ASCVD). The aim of this post-hoc analysis was to compare the effect of hypolipidemic treatment on Lp(a) levels of patients with mixed hyperlipidemia. Material and methods: We previously randomized patients with mixed hyperlipidemia (low-density lipoprotein [LDL-C] > 160 mg/dl and triglycerides > 200 mg/dl) to rosuvastatin monotherapy 40 mg/day (R group, n = 30) or rosuvastatin 10 mg/day combined with fenofibrate 200 mg/day (RF group, n = 30) or omega-3 fatty acids 2 g/day (RΩ group, n = 30). In the present post-hoc analysis, we included only the patients whose Lp(a) levels were assessed (16, 16 and 15 in the R, RF and RΩ groups, respectively). Lipid profile and Lp(a) were measured at baseline and after 3 months of treatment. Results: Significant reductions in total cholesterol, LDL-C, non-high-density lipoprotein-cholesterol (non-HDL-C) and triglyceride levels were observed in all groups. A significant increase in Lp(a) levels was noted in the R (p = 0.017) and RF (p = 0.029) groups, while no significant difference was seen in the RΩ group (p = NS). Regarding Lp(a) elevations, no differences were found between groups. In the R group, a strong negative correlation between the changes in Lp(a) and LDL-C (r = -0.500, p = 0.049) was observed, while a significant negative correlation between the changes in Lp(a) and triglycerides (r = -0.531, p = 0.034) was noted in the RF group. Conclusions: Rosuvastatin and/or fenofibrate treatment increases Lp(a) levels in patients with mixed hyperlipidemia. Novel therapies should target Lp(a) level reduction to decrease the residual ASCVD risk in patients with mixed hyperlipidemia.

NMR-based metabolomic signature: An important tool for the diagnosis and study of pathogenesis of autoimmune hepatitis.

BACKGROUND AND AIMS: Metabolomics is used to predict, diagnose, and monitor metabolic disorders but altered metabolomic signatures have also been reported in diverse diseases, including autoimmune disorders. However, the metabolomic profile in autoimmune hepatitis (AIH) has not been investigated in depth. Therefore, we investigated the metabolomic signature of AIH and its significance as a diagnostic and pathogenetic tool. APPROACH AND RESULTS: Metabolites in plasma samples from 50 patients with AIH at diagnosis, 43 healthy controls, 72 patients with primary biliary cholangitis (PBC), 26 patients with metabolic dysfunction-associated liver disease, and 101 patients with chronic viral hepatitis were determined by 1 H NMR (nuclear magnetic resonance) spectroscopy. Fifty-two metabolites were quantified, and metabolic pathway analysis was performed. Multivariate analysis revealed that AIH could be differentiated from healthy controls and each of the disease controls ( p <0.001). Fifteen metabolites differentiated AIH from disease controls (PBC+chronic viral hepatitis+metabolic dysfunction-associated liver disease) (95% sensitivity and 92% specificity). Ten distinct metabolic pathways were altered in AIH compared to disease controls. The metabolic pathway of branched-chain amino acids (lower valine, leucine, and isoleucine levels and their catabolic intermediates in PBC), methionine (lower methionine, 2-aminobutyrate, and 2-hydroxybutyrate levels in PBC), alanine-aspartate-glutamate (lower metabolites in PBC), and that of metabolites associated with gut microbiota (lower choline, betaine, and dimethylamine levels in PBC) were significantly different between AIH and PBC ( p <0.01). CONCLUSIONS: 1 H NMR spectroscopy could be a promising novel tool to diagnose and study AIH pathogenesis as there is no need for much sample handling, is highly reproducible with high sensitivity and specificity, and low cost.

Insulin resistance and cardiovascular disease.

Insulin resistance (IR) and cardiovascular disease (CVD) represent two universal public health hazards, especially in today's Western societies. A causal-effect relationship has been established that links IR with CVD. The mediating mechanisms are perplexing, under ongoing, rigorous investigation and remain to be fully elucidated. IR is a condition encompassing hyperglycemia and compensatory hyperinsulinemia. It occurs when insulin is not capable of exerting its maximum effects on target tissues, including skeletal muscles, liver and adipose tissue. This alteration of insulin signaling pathways results in the development of cardiometabolic disorders, including obesity, dyslipidemia, low-grade inflammation, endothelial dysfunction and hypertension, all of which are predisposing factors for atherosclerosis and CVD. The management of IR can be achieved through dietary modifications, the inclusion of regular exercise routines in everyday life, pharmacological agents and other interventions tailored to each individual patient's needs. It is important to underline though that, although various antidiabetic drugs that may improve IR are available, no medications are as yet specifically approved for the treatment of IR. This narrative review will focus on the current scientific and clinical evidence pertaining to IR, the mechanisms connecting IR with CVD, as well as plausible strategies for a holistic, personalized approach for IR management.

The Triglyceride/High-Density Lipoprotein Cholesterol (TG/HDL-C) Ratio as a Risk Marker for Metabolic Syndrome and Cardiovascular Disease.

Atherosclerosis is an immunoinflammatory pathological procedure in which lipid plaques are formed in the vessel walls, partially or completely occluding the lumen, and is accountable for atherosclerotic cardiovascular disease (ASCVD). ACSVD consists of three components: coronary artery disease (CAD), peripheral vascular disease (PAD) and cerebrovascular disease (CCVD). A disturbed lipid metabolism and the subsequent dyslipidemia significantly contribute to the formation of plaques, with low-density lipoprotein cholesterol (LDL-C) being the main responsible factor. Nonetheless, even when LDL-C is well regulated, mainly with statin therapy, a residual risk for CVD still occurs, and it is attributable to the disturbances of other lipid components, namely triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C). Increased plasma TG and decreased HDL-C levels have been associated with metabolic syndrome (MetS) and CVD, and their ratio, TG/HDL-C, has been proposed as a novel biomarker for predicting the risk of both clinical entities. Under these terms, this review will present and discuss the current scientific and clinical data linking the TG/HDL-C ratio with the presence of MetS and CVD, including CAD, PAD and CCVD, in an effort to prove the value of the TG/HDL-C ratio as a valuable predictor for each aspect of CVD.

Expanding the Molecular Disturbances of Lipoproteins in Cardiometabolic Diseases: Lessons from Lipidomics.

The increasing global burden of cardiometabolic diseases highlights the urgent clinical need for better personalized prediction and intervention strategies. Early diagnosis and prevention could greatly reduce the enormous socio-economic burden posed by these states. Plasma lipids including total cholesterol, triglycerides, HDL-C, and LDL-C have been at the center stage of the prediction and prevention strategies for cardiovascular disease; however, the bulk of cardiovascular disease events cannot be explained sufficiently by these lipid parameters. The shift from traditional serum lipid measurements that are poorly descriptive of the total serum lipidomic profile to comprehensive lipid profiling is an urgent need, since a wealth of metabolic information is currently underutilized in the clinical setting. The tremendous advances in the field of lipidomics in the last two decades has facilitated the research efforts to unravel the lipid dysregulation in cardiometabolic diseases, enabling the understanding of the underlying pathophysiological mechanisms and identification of predictive biomarkers beyond traditional lipids. This review presents an overview of the application of lipidomics in the study of serum lipoproteins in cardiometabolic diseases. Integrating the emerging multiomics with lipidomics holds great potential in moving toward this goal.

Effect of Clinical and Laboratory Parameters on HDL Particle Composition.

The functional status of High-Density Lipoprotein (HDLs) is not dependent on the cholesterol content but is closely related to structural and compositional characteristics. We reported the analysis of HDL lipidome in the healthy population and the influence of serum lipids, age, gender and menopausal status on its composition. Our sample comprised 90 healthy subjects aged between 30 and 77 years. HDL lipidome was investigated by Nuclear Magnetic Resonance (NMR) spectroscopy. Among serum lipids, triglycerides, apoAI, apoB and the ratio HDL-C/apoAI had a significant influence on HDL lipid composition. Aging was associated with significant aberrations, including an increase in triglyceride content, lysophosphatidylcholine, free cholesterol, and a decrease in esterified cholesterol, phospholipids, and sphingomyelin that may contribute to increased cardiovascular risk. Aging was also associated with an atherogenic fatty acid pattern. Changes occurring in the HDL lipidome between the two genders were more pronounced in the decade from 30 to 39 years of age and over 60 years. The postmenopausal group displayed significant pro-atherogenic changes in HDLs compared to the premenopausal group. The influence of serum lipids and intrinsic factors on HDL lipidome could improve our understanding of the remodeling capacity of HDLs directly related to its functionality and antiatherogenic properties, and also in appropriate clinical research study protocol design. These data demonstrate that NMR analysis can easily follow the subtle alterations of lipoprotein composition due to serum lipid parameters.

A Study of the Metabolic Pathways Affected by Gestational Diabetes Mellitus: Comparison with Type 2 Diabetes.

BACKGROUND: Gestational diabetes mellitus (GDM) remains incompletely understood and increases the risk of developing Diabetes mellitus type 2 (DM2). Metabolomics provides insights etiology and pathogenesis of disease and discovery biomarkers for accurate detection. Nuclear magnetic resonance (NMR) spectroscopy is a key platform defining metabolic signatures in intact serum/plasma. In the present study, we used NMR-based analysis of macromolecules free-serum to accurately characterize the altered metabolic pathways of GDM and assessing their similarities to DM2. Our findings could contribute to the understanding of the pathophysiology of GDM and help in the identification of metabolomic markers of the disease. METHODS: Sixty-two women with GDM matched with seventy-seven women without GDM (control group). 1H NMR serum spectra were acquired on an 11.7 T Bruker Avance DRX NMR spectrometer. RESULTS: We identified 55 metabolites in both groups, 25 of which were significantly altered in the GDM group. GDM group showed elevated levels of ketone bodies, 2-hydroxybutyrate and of some metabolic intermediates of branched-chain amino acids (BCAAs) and significantly lower levels of metabolites of one-carbon metabolism, energy production, purine metabolism, certain amino acids, 3-methyl-2-oxovalerate, ornithine, 2-aminobutyrate, taurine and trimethylamine N-oxide. CONCLUSION: Metabolic pathways affected in GDM were beta-oxidation, ketone bodies metabolism, one-carbon metabolism, arginine and ornithine metabolism likewise in DM2, whereas BCAAs catabolism and aromatic amino acids metabolism were affected, but otherwise than in DM2.

Effect of fixed-dose combination of insulin degludec and liraglutide on apoB-containing lipoprotein subclasses and HDL lipidome in type 2 diabetes.

AIMS: Administration of insulin degludec and liraglutide (IDegLira) correlates to fasting lipid profile changes of diabetic patients, while data concerning apoB-containing lipoprotein subclasses and HDL lipidome are scarce. We evaluated its effect on fasting lipid parameters, apolipoproteins, apoB-containing lipoprotein subclasses and HDL lipidome in patients with type 2 diabetes. METHODS: Sixty three patients with HbA1c > 7 % on oral glucose-lowering drugs received either IDegLira or insulin degludec for 3 months. Lipoprotein subfraction profile was determined through Lipoprint method, whereas HDL lipid composition via 1H NMR. RESULTS: Compared to insulin degludec, IDegLira administration resulted in significantly greater reduction of total and LDL-cholesterol. On the other hand, the effect of the two drugs on apolipoprotein-B-containing lipoprotein subfractions concentration was minimal and did not differ between the 2 interventions. IDegLira, but not insulin degludec, induced an atheroprotective shift in HDL's fatty acid composition and particle core depletion in triglycerides. CONCLUSIONS: IDegLira administration is accompanied by total and LDL-cholesterol reduction, while sdLDL concentration only reduced in patients experiencing triglyceride reduction. IDegLira induced compositional changes of HDL particles. These changes may contribute to the cardioprotective properties of liraglutide.

Omics Analysis of Chemoresistant Triple Negative Breast Cancer Cells Reveals Novel Metabolic Vulnerabilities.

The emergence of drug resistance in cancer poses the greatest hurdle for successful therapeutic results and is associated with most cancer deaths. In triple negative breast cancer (TNBC), due to the lack of specific therapeutic targets, systemic chemotherapy is at the forefront of treatments, but it only benefits a fraction of patients because of the development of resistance. Cancer cells may possess an innate resistance to chemotherapeutic agents or develop new mechanisms of acquired resistance after long-term drug exposure. Such mechanisms involve an interplay between genetic, epigenetic and metabolic alterations that enable cancer cells to evade therapy. In this work, we generated and characterized a chemoresistant TNBC cell line to be used for the investigation of mechanisms that drive resistance to paclitaxel. Transcriptomic analysis highlighted the important role of metabolic-associated pathways in the resistant cells, prompting us to employ 1H-NMR to explore the metabolome and lipidome of these cells. We identified and described herein numerous metabolites and lipids that were significantly altered in the resistant cells. Integrated analysis of our omics data revealed MSMO1, an intermediate enzyme of cholesterol biosynthesis, as a novel mediator of chemoresistance in TNBC. Overall, our data provide a critical insight into the metabolic adaptations that accompany acquired resistance in TNBC and pinpoint potential new targets.

Progressive, Qualitative, and Quantitative Alterations in HDL Lipidome from Healthy Subjects to Patients with Prediabetes and Type 2 Diabetes.

Prediabetes is a clinically silent, insulin-resistant state with increased risk for the development of type 2 diabetes (T2D) and cardiovascular disease (CVD). Since glucose homeostasis and lipid metabolism are highly intersected and interrelated, an in-depth characterization of qualitative and quantitative abnormalities in lipoproteins could unravel the metabolic pathways underlying the progression of prediabetes to T2D and also the proneness of these patients to developing premature atherosclerosis. We investigated the HDL lipidome in 40 patients with prediabetes and compared it to that of 40 normoglycemic individuals and 40 patients with established T2D using Nuclear Magnetic Resonance (NMR) spectroscopy. Patients with prediabetes presented significant qualitative and quantitative alterations, potentially atherogenic, in HDL lipidome compared to normoglycemic characterized by higher percentages of free cholesterol and triglycerides, whereas phospholipids were lower. Glycerophospholipids and ether glycerolipids were significantly lower in prediabetic compared to normoglycemic individuals, whereas sphingolipids were significantly higher. In prediabetes, lipids were esterified with saturated rather than unsaturated fatty acids. These changes are qualitatively similar, but quantitatively milder, than those found in patients with T2D. We conclude that the detailed characterization of the HDL lipid profile bears a potential to identify patients with subtle (but still proatherogenic) abnormalities who are at high risk for development of T2D and CVD.

Environmental Factors Modifying HDL Functionality.

BACKGROUND: Currently, it has been recognized that High-Density Lipoprotein (HDL) functionality plays a much more essential role in protection from atherosclerosis than circulating HDLcholesterol (HDL-C) levels per se. Cholesterol efflux capacity (CEC) from macrophages to HDL has been shown to be a key metric of HDL functionality. Thus, quantitative assessment of CEC may be an important tool for the evaluation of HDL functionality, as improvement of HDL function may lead to a reduction of the risk for Cardiovascular disease (CVD). INTRODUCTION: Although the cardioprotective action of HDLs is exerted mainly through their involvement in the reverse cholesterol transport (RCT) pathway, HDLs have also important anti-inflammatory, antioxidant, antiaggregatory and anticoagulant properties that contribute to their favorable cardiovascular effects. Certain genetic, pathophysiologic, disease states and environmental conditions may influence the cardioprotective effects of HDL either by inducing modifications in lipidome and/or protein composition, or in the enzymes responsible for HDL metabolism. On the other hand, certain healthy habits or pharmacologic interventions may actually favorably affect HDL functionality. METHODS: The present review discusses the effects of environmental factors, including obesity, smoking, alcohol consumption, dietary habits, various pharmacologic interventions, as well as aerobic exercise, on HDL functionality. RESULTS: Experimental and clinical studies or pharmacological interventions support the impact of these environmental factors in the modification of HDL functionality, although the involved mechanisms are not fully understood. CONCLUSION: Further research should be conducted to identify the underlying mechanisms of these environmental factors and to identify new pharmacologic interventions capable of enhancing CEC, improving HDL functionality and potentially improving cardiovascular risk.

Altered RBC membrane lipidome: A possible etiopathogenic link for the microvascular impairment in Type 2 diabetes.

AIMS: Disturbances in red blood cells' (RBCs) membrane structure, that result in altered rheological properties, have been implicated in the pathogenesis of microvascular complications of diabetes mellitus(T2DM). However, the compositional alterations in RBCs membranes of T2DM patients have not been characterized in detail. METHODS: NMR-based lipidomic approach used for the global investigation of the lipidome of RBCs membrane in 20 newly diagnosed T2DM patients. Twenty healthy individuals served as controls. RESULTS: In the lipidomic analysis, the discrimination power among the two groups was of high significance. T2DM patients characterized by an increased content of cholesterol, total sphingolipids, sphingomyelin and glycolipids, and decreased total phospholipids, mainly due to phosphatidylethanolamine, total ether glycerolipids and plasmalogen-phospholipids, and higher cholesterol-to-phospholipids molecular ratio compared to controls. In T2DM, lipids were esterified with saturated rather than unsaturated fatty acids, an atherogenic pattern that may be involved in the impairment of membrane fluidity and rigidity. CONCLUSIONS: NMR-based lipidomic analysis of RBCs can provide insights into molecular lipid features of membrane microenvironment that influence their vital function and rheological behavior in microvascular network in T2DM.Early identification of these disturbances, even before the onset of diabetes, could critically help to the development of novel preventative and curative therapies for reducing the risk of microvascular dysfunction.

Mediterranean Diet Implementation to Protect against Advanced Lung Cancer Index (ALI) Rise: Study Design and Preliminary Results of a Randomised Controlled Trial.

The Mediterranean diet (MD) has been inversely associated with lung cancer (LC) risk. Hereby we show the preliminary results of our prospective randomised controlled trial in inflammatory and nutritional status of LC patients after 3-month implementation of MD. In total, 30 patients with small-cell or non-small-cell LC (stages III-IV) were enrolled. They were randomly assigned either to Control group, receiving general nutritional guidelines, or the MD group, in which a personalised MD plan was provided. Medical and dietary history, anthropometrics, blood biomarkers, and circulating antioxidant vitamins were assessed. The main outcome was a significantly higher advanced lung cancer inflammation index (ALI) in patients of the control arm than those following MD (p = 0.003). In the MD group, platelets were significantly reduced at the study endpoint (p = 0.044). BMI and body fat mass remained unchanged in both arms, but serum glucose was significantly higher in control compared to MD group (p = 0.017). In conclusion, we showed for the first time that implementing a personalised MD for 3 months is promising to regulate prognostic biomarkers in advanced LC. The final results of our on-going trial will shed a light on the inflammatory, antioxidant and nutritional status of LC patients following MD.

Effect of Dapagliflozin on Urine Metabolome in Patients with Type 2 Diabetes.

CONTEXT: Inhibitors of sodium-glucose cotransporters-2 have cardio- and renoprotective properties. However, the underlying mechanisms remain indeterminate. OBJECTIVE: To evaluate the effect of dapagliflozin on renal metabolism assessed by urine metabolome analysis in patients with type 2 diabetes. DESIGN: Prospective cohort study. SETTING: Outpatient diabetes clinic of a tertiary academic center. PATIENTS: Eighty patients with hemoglobin A1c > 7% on metformin monotherapy were prospectively enrolled. INTERVENTION: Fifty patients were treated with dapagliflozin for 3 months. To exclude that the changes observed in urine metabolome were merely the result of the improvement in glycemia, 30 patients treated with insulin degludec were used for comparison. MAIN OUTCOME MEASURE: Changes in urine metabolic profile before and after the administration of dapagliflozin and insulin degludec were assessed by proton-nuclear magnetic resonance spectroscopy. RESULTS: In multivariate analysis urine metabolome was significantly altered by dapagliflozin (R2X = 0.819, R2Y = 0.627, Q2Y = 0.362, and coefficient of variation analysis of variance, P < 0.001) but not insulin. After dapagliflozin, the urine concentrations of ketone bodies, lactate, branched chain amino acids (P < 0.001), betaine, myo-inositol (P < 0001), and N-methylhydantoin (P < 0.005) were significantly increased. Additionally, the urine levels of alanine, creatine, sarcosine, and citrate were also increased (P < 0001, P <0.0001, and P <0.0005, respectively) whereas anserine decreased (P < 0005). CONCLUSIONS: Dapagliflozin significantly affects urine metabolome in patients with type 2 diabetes in a glucose lowering-independent way. Most of the observed changes can be considered beneficial and may contribute to the renoprotective properties of dapagliflozin.

Early Signs of Atherogenic Features in the HDL Lipidomes of Normolipidemic Patients Newly Diagnosed with Type 2 Diabetes.

Cardiovascular disease (CVD) is the major cause of death in patients with type-2 diabetes mellitus (T2DM), although the factors that accelerate atherosclerosis in these patients are poorly understood. The identification of the altered quantity and quality of lipoproteins, closely related to atherogenesis, is limited in routine to a pattern of high triglycerides and low HDL-cholesterol (HDL-C) and in research as dysfunctional HDLs. We used the emerging NMR-based lipidomic technology to investigate compositional features of the HDLs of healthy individuals with normal coronary arteries, drug-naïve; recently diagnosed T2DM patients with normal coronary arteries; and patients with recent acute coronary syndrome. Patients with T2DM and normal serum lipid profiles even at diagnosis presented significant lipid alterations in HDL, characterized by higher triglycerides, lysophosphatidylcholine and saturated fatty acids; and lower cholesterol, phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, plasmalogens and polyunsaturated fatty acids, an atherogenic pattern that may be involved in the pathogenesis of atherosclerosis. These changes are qualitatively similar to those found, more profoundly, in normolipidemic patients with established Coronary Heart Disease (CHD). We also conclude that NMR-based lipidomics offer a novel holistic exploratory approach for identifying and quantifying lipid species in biological matrixes in physiological processes and disease states or in disease biomarker discovery.

Lipidomics in non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disorder in Western countries, comprises steatosis to nonalcoholic steatohepatitis (NASH), with the latter having the potential to progress to cirrhosis. The transition from isolated steatosis to NASH is still poorly understood, but lipidomics approach revealed that the hepatic lipidome is extensively altered in the setting of steatosis and steatohepatitis and these alterations correlate with disease progression. Recent data suggest that both quantity and quality of the accumulated lipids are involved in pathogenesis of NAFLD. Changes in glycerophospholipid, sphingolipid, and fatty acid composition have been described in both liver biopsies and plasma of patients with NAFLD, implicating that specific lipid species are involved in oxidative stress, inflammation, and cell death. In this article, we summarize the findings of main human lipidomics studies in NAFLD and delineate the currently available information on the pathogenetic role of each lipid class in lipotoxicity and disease progression.

Cardioprotective Properties of HDL: Structural and Functional Considerations.

BACKGROUND: As Mendelian Randomization (MR) studies showed no effect of variants altering HDL-cholesterol (HDL-C) levels concerning Cardiovascular Disease (CVD) and novel therapeutic interventions aiming to raise HDL-C resulted to futility, the usefulness of HDL-C is unclear. OBJECTIVE: As the role of HDL-C is currently doubtful, it is suggested that the atheroprotective functions of HDLs can be attributed to the number of HDL particles, and their characteristics including their lipid and protein components. Scientific interest has focused on HDL function and on the causes of rendering HDL particles dysfunctional, whereas the relevance of HDL subclasses with CVD remains controversial. METHODS: The present review discusses changes in quality as much as in quantity of HDL in pathological conditions and the connection between HDL particle concentration and cardiovascular disease and mortality. Emphasis is given to the recently available data concerning the cholesterol efflux capacity and the parameters that determine HDL functionality, as well as to recent investigations concerning the associations of HDL subclasses with cardiovascular mortality. RESULTS: MR studies or pharmacological interventions targeting HDL-C are not in favor of the hypothesis of HDL-C levels and the relationship with CVD. The search of biomarkers that relate with HDL functionality is needed. Similarly, HDL particle size and number exhibit controversial data in the context of CVD and further studies are needed. CONCLUSION: There is no room for the old concept of HDL as a silver bullet,as HDL-C cannot be considered a robust marker and does not reflect the importance of HDL particle size and number. Elucidation of the complex HDL system, as well as the finding of biomarkers, will allow the development of any HDL-targeted therapy.

Lipidome of plasma lipoproteins and liver is zinc- modulated in High fat diet treated mice.

Zinc (Zn) and Zn-transcription Factors regulate the metabolic pathways of lipids and glucose, consequently nutritional zinc deficiency or excess, activates stress pathways and deranges the hepatic metabolism of lipids. High fat diet (HFD) also leads to lipids' profile disorders as well as to intracellular free radicals (FR) accumulation and finally to metabolic stress-syndrome. Study of nutritional Zn effects on the lipidome of plasma lipoproteins and liver, in HFD-mice, was the aim of the present research. Three Zn enriched HF-Diets as follows, 3 mg/kg feed (Zn deficient diet), 30 mg/kg feed (Zn sufficient diet), 300mgZn /kg feed (Zn excess diet) (Mucedola s.r.l Italy-55% cal) were applied respectively to three groups of male wild type (wt) mice (Hybrid F1/F1),C57Bl/6xCBA, one month old, for 10 weeks. Accordingly, mice body weight rate and 1H-NMR spectrum analysis of liver extracts and plasma HDL and non-HDL lipoproteins were evaluated at the end of the experimental period. It is concluded that Zn sufficient diet (30 mg/Kg Feed) creates a highly protective lipidomic profile on plasma and liver lipoproteins of HFD-mice, related to significantly increased antiatherogenic indicators in lipids' composition, compared to mice in nutritional Zn deficiency or excess.

Sitosterolemia: A multifaceted metabolic disorder with important clinical consequences.

Sitosterolemia is a metabolic disorder characterized by increased intestinal absorption and tissue accumulation of phytosterols. Although sitosterolemia is considered a rare disease, its prevalence may be significantly higher than initially thought. Indeed, accumulating evidence suggests that patients with unexplained hematologic abnormalities or premature cardiovascular disease in the absence of classic risk factors may exhibit disordered phytosterol metabolism. In this review, we present a patient with sitosterolemia, describe the pathophysiology and the clinical picture of this disorder, and discuss the clinical value of phytosterol supplementation in patients with primary dyslipidemias.