Manifestation Of Metabolic Syndrome Research Articles

Tracking biochemical changes induced by iron loading in AML12 cells with synchrotron live cell, time-lapse infrared microscopy

Hepatocytes are essential for maintaining the homeostasis of iron and lipid metabolism in mammals. Dysregulation of either iron or lipids has been linked with serious health consequences, including non-alcoholic fatty liver disease (NAFLD). Considered the hepatic manifestation of metabolic syndrome, NAFLD is characterised by dysregulated lipid metabolism leading to a lipid storage phenotype. Mild to moderate increases in hepatic iron have been observed in ∼30% of individuals with NAFLD; however, direct observation of the mechanism behind this increase has remained elusive. To address this issue, we sought to determine the metabolic consequences of iron loading on cellular metabolism using live cell, time-lapse Fourier transform infrared (FTIR) microscopy utilising a synchrotron radiation source to track biochemical changes. The use of synchrotron FTIR is non-destructive and label-free, and allowed observation of spatially resolved, sub-cellular biochemical changes over a period of 8 h. Using this approach, we have demonstrated that iron loading in AML12 cells induced perturbation of lipid metabolism congruent with steatosis development. Iron-loaded cells had approximately three times higher relative ester carbonyl concentration compared with controls, indicating an accumulation of triglycerides. The methylene/methyl ratio qualitatively suggests the acyl chain length of fatty acids in iron-loaded cells increased over the 8 h period of monitoring compared with a reduction observed in the control cells. Our findings provide direct evidence that mild to moderate iron loading in hepatocytes drives de novo lipid synthesis, consistent with a role for iron in the initial hepatic lipid accumulation that leads to the development of hepatic steatosis.

Dual-specificity phosphatase 3 deletion promotes obesity, non-alcoholic steatohepatitis and hepatocellular carcinoma

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic hepatic pathology in Western countries. It encompasses a spectrum of conditions ranging from simple steatosis to more severe and progressive non-alcoholic steatohepatitis (NASH) that can lead to hepatocellular carcinoma (HCC). Obesity and related metabolic syndrome are important risk factors for the development of NAFLD, NASH and HCC. DUSP3 is a small dual-specificity protein phosphatase with a poorly known physiological function. We investigated its role in metabolic syndrome manifestations and in HCC using a mouse knockout (KO) model. While aging, DUSP3-KO mice became obese, exhibited insulin resistance, NAFLD and associated liver damage. These phenotypes were exacerbated under high fat diet (HFD). In addition, DEN administration combined to HFD led to rapid HCC development in DUSP3-KO compared to wild type (WT) mice. DUSP3-KO mice had more serum triglycerides, cholesterol, AST and ALT compared to control WT mice under both regular chow diet (CD) and HFD. The level of fasting insulin was higher compared to WT mice, though, fasting glucose as well as glucose tolerance were normal. At the molecular level, HFD led to decreased expression of DUSP3 in WT mice. DUSP3 deletion was associated with increased and consistent phosphorylation of the insulin receptor (IR) and with higher activation of the downstream signaling pathway. In conclusion, our results support a new role for DUSP3 in obesity, insulin resistance, NAFLD and liver damage.

From Nonalcoholic Fatty Liver Disease (NAFLD) to Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD)-New Terminology in Pediatric Patients as a Step in Good Scientific Direction?

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world, which predispose to more serious hepatic conditions. It ranges from simple liver steatosis to nonalcoholic steatohepatitis (NASH), which may progress to cirrhosis, and even end-stage liver disease. Since obesity became one of the most important health concerns wordwide, a considerable increase in the prevalance of NAFLD and other metabolic implications has been observed, both in adults and children. Due to the coexistence of visceral obesity, insulin resistance, dyslipidemia, NAFLD is considered to be the hepatic manifestation of metabolic syndrome (MetS). These relationships between NAFLD and MetS led to the set up in adults of a new term combining both of these conditions, called metabolic dysfunction-associated fatty liver disease (MAFLD). Based on these findings, we propose a set of criteria, which may be useful to diagnose MAFLD in children and adolescents.

Cardiovascular involvement after liver transplantation: role of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis

Patients submitted to liver transplantation (LT) are exposed to high risk of cardiovascular (CV) complications which are the main determinants of both short-term and long-term morbidity and mortality in LT. Non-alcoholic fatty liver disease (NAFLD) is a very frequent condition in general population and is associated with a high risk of cardiovascular disease (CVD) which represents the first cause of death of these patients. NAFLD is predicted to become the first indication to LT and nowadays is also frequently detected in patients submitted to LT for other indications. Thus, the risk of CVD in patients submitted to LT is forecasted to increase in the next years. In this review the extent of CV involvement in patients submitted to LT and the role of NAFLD, either recurring after transplantation or as de novo presentation, in increasing CV risk is analysed. The risk of developing metabolic alterations, including diabetes, hypertension, dyslipidemia and weight gain, all manifestations of metabolic syndrome, occurring in the first months after LT, is depicted. The different presentations of cardiac involvement, represented by early atherosclerosis, coronary artery disease, heart failure and arrhythmias in patients with NAFLD submitted to LT is described. In addition, the tools to detect cardiac alterations either before or after LT is reported providing the possibility for an early diagnosis of CVD and an early therapy able to reduce morbidity and mortality for these diseases. The need for long-term concerted multidisciplinary activity with dietary counseling and exercise combined with drug treatment of all manifestations of metabolic syndrome is emphasized.

The Current View of Nonalcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma.

Simple SummaryThe incidence of nonalcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC) is increasing. However, an effective screening or surveillance method is not established. Recently, the NAFLD/nonalcoholic steatohepatitis (NASH) guidelines of Japan were revised to incorporate new strategies and evidence for the management and surveillance of NAFLD/NASH. Advanced fibrosis and lifestyle-related and metabolic comorbidities, especially obesity and diabetes mellitus, are associated with HCC development. At the first screening, serum markers of hepatic fibrosis (hyaluronic acid, type IV collagen 7S, and mac-2 binding protein), or the fibrosis (FIB)-4 index or the nonalcoholic fatty liver disease fibrosis score (NFS), or a platelet count should be evaluated. When liver fibrosis is indicated, consultation with a gastroenterology specialist should be considered for the second screening. The risk of HCC should be stratified using the FIB-4 index or the NFS. Liver stiffness should be measured using vibration-controlled transient elastography in those at intermediate or high risk. Blood tests and imaging should be performed every 6–12 months in patients with advanced fibrosis for HCC surveillance. We review here what is known about NAFLD-HCC and provide perspectives for future research.Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and can develop into hepatocellular carcinoma (HCC). The incidence of NAFLD-related HCC, which is accompanied by life-threatening complications, is increasing. Advanced fibrosis and lifestyle-related and metabolic comorbidities, especially obesity and diabetes mellitus, are associated with HCC development. However, HCC is also observed in the non-cirrhotic liver. Often, diagnosis is delayed until the tumor is relatively large and the disease is advanced; an effective screening or surveillance method is urgently required. Recently, the NAFLD/nonalcoholic steatohepatitis (NASH) guidelines of Japan were revised to incorporate new strategies and evidence for the management and surveillance of NAFLD/NASH. Fibrosis must be tested for noninvasively, and the risk of carcinogenesis must be stratified. The treatment of lifestyle-related diseases is expected to reduce the incidence of NAFLD and prevent liver carcinogenesis.

Non-Alcoholic Fatty Liver Disease: From Pathogenesis to Clinical Impact

Non-Alcoholic Fatty Liver Disease (NAFLD) is caused by the accumulation of fat in over 5% of hepatocytes in the absence of alcohol consumption. NAFLD is considered the hepatic manifestation of metabolic syndrome (MS). Recently, an expert consensus suggested as more appropriate the term MAFLD (metabolic-associated fatty liver disease). Insulin resistance (IR) plays a key role in the development of NAFLD, as it causes an increase in hepatic lipogenesis and an inhibition of adipose tissue lipolysis. Beyond the imbalance of adipokine levels, the increase in the mass of visceral adipose tissue also determines an increase in free fatty acid (FFA) levels. In turn, an excess of FFA is able to determine IR through the inhibition of the post-receptor insulin signal. Adipocytes secrete chemokines, which are able to enroll macrophages inside the adipose tissue, responsible, in turn, for the increased levels of TNF-α. The latter, as well as resistin and other pro-inflammatory cytokines such as IL-6, enhances insulin resistance and correlates with endothelial dysfunction and an increased cardiovascular (CV) risk. In this review, the role of diet, intestinal microbiota, genetic and epigenetic factors, low-degree chronic systemic inflammation, mitochondrial dysfunction, and endoplasmic reticulum stress on NAFLD have been addressed. Finally, the clinical impact of NAFLD on cardiovascular and renal outcomes, and its direct link with type 2 diabetes have been discussed.

Immunity as Cornerstone of Non-Alcoholic Fatty Liver Disease: The Contribution of Oxidative Stress in the Disease Progression.

Non-alcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome and has become the major cause of chronic liver disease, especially in western countries. NAFLD encompasses a wide spectrum of hepatic histological alterations, from simple steatosis to steatohepatitis and cirrhosis with a potential development of hepatocellular carcinoma. Non-alcoholic steatohepatitis (NASH) is characterized by lobular inflammation and fibrosis. Several studies reported that insulin resistance, redox unbalance, inflammation, and lipid metabolism dysregulation are involved in NAFLD progression. However, the mechanisms beyond the evolution of simple steatosis to NASH are not clearly understood yet. Recent findings suggest that different oxidized products, such as lipids, cholesterol, aldehydes and other macromolecules could drive the inflammation onset. On the other hand, new evidence indicates innate and adaptive immunity activation as the driving force in establishing liver inflammation and fibrosis. In this review, we discuss how immunity, triggered by oxidative products and promoting in turn oxidative stress in a vicious cycle, fuels NAFLD progression. Furthermore, we explored the emerging importance of immune cell metabolism in determining inflammation, describing the potential application of trained immune discoveries in the NASH pathological context.

Metal Ion Transportation Patterns and Chemokines Level Highlight from the Point of View of the Innate Immune System in the Formation of Non-alcoholic Fatty Liver Disease

Purpose: Non-alcoholic fatty liver disease (NAFLD), including non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH), represents the hepatic manifestation of obesity and metabolic syndrome. NAFLD covers a spectrum of disorders ranging from simple steatosis to non-alcoholic NASH and cirrhosis, which properly can develop into liver cancer. In our research, we use bioinformatics methods to evaluate the biological progress changes from normal liver to non-alcoholic fatty liver disease. Method: We downloaded the data from the NCBI GEO database and begin the analysis of the GSE151158, after using three common different expression genes analysis of R language, including edgR, DESeq2, and limma. We found the common gene set in the transcriptional progress which contains 270 genes in the threshold of p<0.05. After that, Gene set enrichment analysis(GSEA) is performed to find the important biological function or module in the formation of Non-alcoholic fatty liver disease. Results: By using the bioinformatics method, we found 270 differently expressed genes(DEGs) in the progress of formation of Non-alcoholic fatty liver disease. Gene set enrichment analysis is performed to find the enriched functions. We found that 13 metal ion transport or metabolism-related and 3 chemokine-related genes were enriched. The metal ion transport or metabolism-related genes mostly get negative enrichment scores, while most chemokines-related genes got positive enrichment scores. Conclusion: The results we obtained from the research meant that metal ion transportation patterns and abnormal chemokines played several key roles from the point of view of the innate immune system in the formation of non-alcoholic fatty liver disease. As an early stage of non-alcoholic fatty liver disease, this finding will help us to understand the disease mechanism and design effective drugs to prevent the development and deterioration of the non-alcoholic fatty liver disease.

Echogenicity and stiffness coefficient of the liver tissue in comparison with similar indicators of the renal parenchyma as an early manifestation of metabolic syndrome

Echogenicity and stiffness coefficient of the liver tissue in comparison with similar indicators of the renal parenchyma as an early manifestation of metabolic syndrome

Non-alcoholic fatty liver disease and lipotoxicity.

Non-alcoholic fatty liver disease (NAFLD) has become the most common liver pathology worldwide due to the rising prevalence of obesity. This term includes changes from simple steatosis to steatohepatitis and fibrosis. It was previously thought to be a hepatic manifestation of metabolic syndrome, but recent literature describes this relation as much more complex and bi-directional. Development of NAFLD is associated with other metabolic syndrome components but it can also exacerbate insulin resistance and increase cardiovascular risk. Recently a lot of attention is brought to the role of lipids and lipotoxicity in pathogenesis and progression of non-alcoholic fatty disease. It seems that some lipid classes can be protective against liver injury while others are harmful in excessive amounts. This study presents an overview of the main lipids involved in the pathogenesis of non-alcoholic fatty liver disease and summarizes their association with lipotoxicity, insulin resistance, oxidative stress and other processes responsible for its progression.

Biochemical Parameters as Predictors of Underlying Liver Disease in Patients with Chronic Kidney Disorders.

Background:Non-alcoholic fatty liver disease (NAFLD) is an increasingly common cause of chronic liver disease and is becoming a major public health problem. NAFLD has been recognized as a hepatic manifestation of metabolic syndrome, associated with systemic diseases such as cardiovascular disease (CVD) and chronic kidney disease (CKD).Objective:The aim of this study was to examine the role of serum LFT parameters and renal function parameters as predictors of unmanifested liver disease.Methods:In this study, the presence of possible liver disease detected by biochemical parameters and confirmed by Transient Liver Elastography (TE) in a group of patients with different stages of chronic kidney disease (CKD) was investigated. Patients with various stages of CKD were divided into five subgroups regarding aetiology: nephroangiosclerosis, diabetic nephropathy, glomerulonephritis and pyelonephritis, autoimmune kidney disease, and polycystic and another morphological kidney disease. Liver stiffness was used to quantify liver fibrosis while Controlled attenuation parameter (CAP) was used to quantify liver steatosis. Functional liver tests and biochemical parameters of kidney function were measured in all patients.Results:Statistical analysis used in this study was a decision tree as a predictive model to map observed variables resulting in the conclusion about outcomes. The application of existing laboratory parameters, in combination with other parameters in presence of the defined etiological factors of kidneys diseases, indicate development of hepatic diseases. Higher values of phosphorus and low values of ferritin in patients with autoimmune kidney disease, and polycystic and another morphological kidney disease, expresses steatosis of the hepatic parenchyma.Conclusion:In contrary, low values of phosphorus and higher values of ferritin in patients with nephroangiosclerosis, diabetic nephropathy, glomerulonephritis and pyelonephritis, are in a favour steatosis of the hepatic parenchyma. Serum values of phosphorus and ferritin are valuable predictors of the liver disease in patients with end-stage kidney diseases of different aetiology.

In Vitro and In Vivo Models of Non-Alcoholic Fatty Liver Disease: A Critical Appraisal.

Non-alcoholic fatty liver disease (NAFLD), including non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH), represents the hepatic manifestation of obesity and metabolic syndrome. Due to the spread of the obesity epidemic, NAFLD is becoming the most common chronic liver disease and one of the principal indications for liver transplantation. However, no pharmacological treatment is currently approved to prevent the outbreak of NASH, which leads to fibrosis and cirrhosis. Preclinical research is required to improve our knowledge of NAFLD physiopathology and to identify new therapeutic targets. In the present review, we summarize advances in NAFLD preclinical models from cellular models, including new bioengineered platforms, to in vivo models, with a particular focus on genetic and dietary mouse models. We aim to discuss the advantages and limits of these different models.

FABP4 inhibitor attenuates inflammation and endoplasmic reticulum stress of islet in leptin receptor knockout rats.

Metabolic syndrome is characterized by abdominal obesity, hypertriglyceridemia and hyperglycemia. Fatty acid binding protein 4 (FABP4), as a member of intracellular lipid chaperones, is not only engaged in lipid transport but involved in inflammation and insulin resistance. The present study was to investigate the effects of BMS309403, a specific FABP4 inhibitor, on metabolic syndrome and its possible molecular mechanisms in islets. Leptin receptor knockout (Lepr-/-) rat, a novel and representative animal model of metabolic syndrome, was adopted in this study. Lepr-/- male rats and their wild littermates were grouped and intragastrically administered with BMS309403. Glucose Tolerance Test (GTT) and Insulin Tolerance Test (ITT) were performed on all rats. Serum insulin was detected by ELISA. The metabolic characters, as well as liver and kidney functions, were evaluated by serum biochemical assay. Immunohistochemistry and Western blot were adopted to detect the expression levels of FABP4, CD68, GRP78, ATF6, p-IRE1a, and Cleaved caspase-3. Lepr-/- rats showed prominent characteristics of metabolic syndrome with increased FABP4, inflammatory infiltration, ER stress and apoptosis in islets. BMS309403 administration attenuated inflammation, ER stress and apoptosis in Lepr-/- rat islets while stimulating insulin secretion as well as improving manifestation of metabolic syndrome without hepatic and renal toxicity. FABP4 increased in Lepr-/- rat islets and might be involved in the regulation of islet inflammation and apoptosis via ER stress. FABP4 inhibitor BMS309403 could ameliorate islet inflammation and apoptosis in metabolic syndrome through suppressing ER stress.

Non-alcoholic fatty liver disease and left ventricular diastolic dysfunction in patients with metabolic syndrome

The purpose of the study was to determine the frequency and nature of manifestations of left ventricular diastolic dysfunction in patients with non-alcoholic fatty liver disease with the background of metabolic syndrome (MS).Characteristics of patients and research methods: To solve this problem, 227 patients with MS (130 men and 97 women) were examined. The study was conducted in two phases. At the first stage, all patients with MS are divided into two groups: patients with NAFLD — 205 people and 22 — without liver damage. At the next stage, a group of NAFLD patients with left ventricular DD (n=136) (66.34%) (the main group) and patients with no DD (n=69) (33.66%) (the comparison group) were identified.Results of the study: the results of diagnostics, clinical and laboratory manifestations of left ventricular diastolic dysfunction in 136 patients with NAFLD on the background of metabolic syndrome are Presented. Significant factors of development and progression of diastolic dysfunction were identified, which include increased body weight and adipose tissue, insulin resistance, dyslipidemia, hyperuricemia, activity and stage of liver damage. According to the data of structural and functional changes in the myocardium, the role of diastolic dysfunction in the development of chronic heart failure in patients with NAFLD with manifestations of metabolic syndrome has been established.Conclusion: it was Found that the development of left ventricular diastolic dysfunction in patients with NAFLD is due to the morphofunctional state of the liver.

The role of bile acids in the variety of mechanisms of the formation of hepatic manifestations of metabolic syndrome

Metabolic syndrome and non-alcoholic fatty liver disease, as its hepatic manifestation, are extremely relevant and socially significant health problems today. The article presents new data on the problem of the pathogenesis of non-alcoholic fatty liver disease from the perspective of the influence of bile acids on the state of carbohydrate and lipid metabolism, the functioning of adipose tissue, the composition and function of the intestinal microbial-tissue complex. Bile acids are ligand-binding domains involved in the activation of many receptors. The role of endogenous fructose, uric acid, chronic kidney disease, platelet dysfunction in the development of the disease is highlighted, the directions of therapeutic action are determined. An increase in oxidative stress, a violation of the intestinal microbial-tissue complex, dyslipidemia, and excessive platelet activation form a “vicious circle” that promotes the progression of liver and kidney diseases.

Influence of obesity and epicardial fat on the progression of electrical and structural remodeling in a canine obese rapid atrial pacing model

Abstract Background Metabolic syndrome is a cluster of conditions including obesity, insulin resistance, hypertension, and abnormal cholesterol, which increases the cardiovascular risk. Metabolic syndrome or obesity has been reported to provide systemic inflammation and oxidative stress. Increased epicardial fat volume is a manifestation of obesity or metabolic syndrome. Those systemic and local conditions related to obesity or metabolic syndrome have been linking to the risk of atrial fibrillation (AF). The underlying mechanisms of obesity linking epicardial fat to AF progression have not been fully examined. Purpose To investigate the impact of obesity linked to epicardial fat on electrophysiologic and anatomical AF substrates. Methods Twenty dogs aged 3 years were divided into four groups (n=5 per each): normal diet for over 20 weeks (control group [median body weight: 12.0 kg]), rapid atrial pacing (RAP) for last 4–15 (median 8) weeks during a normal diet for the same period (RAP group [10.5 kg]), high-fat diet (HFD) maintained for over 20 weeks without RAP (MetS group [16.0 kg]), and RAP for last 4–12 (median 6) weeks during HFD maintained for 24 weeks (MetS-RAP group [17.0 kg]), respectively. Activation/voltage maps of the atria during sinus rhythm were created with Ensite NavX mapping system. The effective refractory period (ERP) at 5 left atrial (LA) and pulmonary vein (PV) sites (LA appendage [LAA], LA body, right and left superior PVs, and inferior PV), and AF inducibility by burst LAA pacing were determined. At study completion, hearts were excised for histopathological and gene expression analyses. Results The LA pressure was more significantly increased in MetS than the MetS-RAP, RAP, and control groups (22.5 [17–28.8] mmHg vs. 14.0 [10.5–16.3] mmHg, 10.5 [7.4–17.2] mmHg and 10.7 [9.6–13.5] mmHg, respectively, P&amp;lt;0.05). The LA/PV ERP at a basic cycle length of 400 ms was shorter in the MetS-RAP and RAP than MetS and control groups (118±39 ms and 122±44 ms vs. 136±18 ms and 155±39 ms, respectively, P&amp;lt;0.05). Short duration AF was more induced in the MetS and MetS-RAP than RAP and control groups (3 [0–5.5] sec and 2 [0.5–3.5] sec vs. 0 [0–4.5] sec and 0 [0–0] sec, P&amp;lt;0.05). Histological examinations showed the fatty infiltration extending from epicardial fat increased more in the Mets and Mets-RAP than RAP and control groups (Figure). The Fibronectin 1 and collagen I/III mRNA levels increased more in the MetS-RAP and AF than MetS and control groups. Conclusions AF vulnerability was associated with increased LA pressures and fibrofatty infiltration from epicardial fat in the MetS group, and with fibrofatty infiltration from epicardial fat with subtle fibrosis in the MetS-RAP group. This suggested that fibrofatty infiltration and epicardial fat plays an important role in AF pathogenesis in obese patients. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Grant-in-Aid for Scientific Research (KAKENHI)

Effects of TNF-α antagonist infliximab on fructose-induced metabolic syndrome in rats.

Public health issues have been raised regarding fructose toxicity and its serious metabolic disorders. Deleterious effects of high fructose intake on insulin sensitivity, body weight, lipid homeostasis have been identified. The new millennium has witnessed the emergence of a modern epidemic, the metabolic syndrome (MS), in approximately 25% of the world's adult population. The current study aimed to investigate the effect of the TNF-α antagonist infliximab on fructose-induced MS in rats. Rats were administered fructose (10%) in drinking water for 12 weeks to induce the experimental MS model. infliximab (5 mg/kg) was injected once weekly intraperitoneally starting on the 13th week for 4 weeks. Increase in body weight, blood glucose level, serum triglycerides (TGs), adiponectin level and blood pressure were present in MS rats. They also prompted increases in serum of leptin, TNF-α, and malondialdehyde (MDA) levels. Treatment with infliximab did not affect body weight, hyperglycemia or hypertension, but decreased serum TGs and increased serum HDL-c levels. Infliximab also decreased adiponectin levels. Surprisingly, infliximab increased MDA above its value in the MS group. These results reflect the fact that infliximab affects the manifestations of MS in rats. Though infliximab reduced TGs, increased HDL-c levels, reversed adiponectin resistance occurred by fructose, the drug failed to combat MS-mediated hyperglycemia, hypertension, and elevated MDA above the insult.

Hepatoprotective Evidence of Hydroxytyrosol Against Non-alcoholic Fatty Liver in Animal Models

Background:: Non-alcoholic fatty liver (NAFLD) is a metabolic disorder characterized by an excessive accumulation of fat in hepatocytes. It is a condition directly related to being overweight and is considered as a manifestation of metabolic syndrome. The progressive increase in its incidence due to the global increase in obesity, together with the absence of effective pharmacological treatment, makes it necessary to find new strategies to reduce or reverse its development and progression. In this sense, natural compounds can be potential targets for their remarkable biological activity and low toxicity. Hydroxytyrosol (HT) is a phenolic compound mainly found in olive oil and in olive leaves with antioxidant, anti-inflammatory and cardiovascular properties, among others. Objective:: This document analyses the available information on the potential beneficial effects of the administration of HT against NAFLD. Results:: Studies with animal models have shown promising results by reducing the degree of steatosis, oxidative stress, inflammation, and improving liver function. The effects of HT derive from its direct antioxidant and anti-inflammatory activity, but also from regulating the activity of various signalling pathways. Conclusion:: The consumption of HT, preferably associated with virgin olive oil, combined with an adequate diet and a healthy lifestyle, may be a strategy to consider preventing or reversing liver steatosis. However, well-designed clinical trials are still necessary to determine their real usefulness in human patients.

Relationship between non-alcoholic fatty liver disease and coronary heart disease.

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease and considered a liver manifestation of metabolic syndrome. It is in close relationship with insulin resistance, obesity, diabetes mellitus, all of which increase risk of cardiovascular disease (CVD). Besides, many studies point out that NAFLD independently contributes to the development of atherosclerosis and CHD. On the other hand, CVDs are the leading cause of death in NAFLD patients. Many pathophysiological changes and molecular mechanisms play an important role in NAFLD for CVD formation. Atherosclerosis is common in NAFLD, which also mainly contributes to the CVD formation and CHD. Many studies linking atherosclerotic CHD and NAFLD are present in the literature. Subclinical CHD, mainly detected by coronary computed tomography views, have been detected more common in NAFLD patients. Presence of NAFLD has been found to be more common in patients with severe CHD and in stable CHD, NAFLD has been found to be associated with more diffuse disease. In acute coronary syndromes, especially in acute myocardial infarction, patients with NAFLD have been found to have poor prognosis when compared with NAFLD free patients. In this review, our aim is to evaluate the relationship between NAFLD and CHD in detail and go over the pathophysiological mechanisms underlying this relationship.

Bilberry Anthocyanins Ameliorate NAFLD by Improving Dyslipidemia and Gut Microbiome Dysbiosis.

Non-alcoholic fatty liver disease (NAFLD) is a manifestation of metabolic syndrome closely linked to dyslipidemia and gut microbiome dysbiosis. Bilberry anthocyanins (BA) have been reported to have preventive effects against metabolic syndrome. This study aimed to investigate the protective effects and mechanisms of BA in a Western diet (WD)-induced mouse model. The results revealed that supplementation with BA attenuated the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), low-density lipoprotein cholesterol (LDL-c), fat content in liver, 2-thiobarbituric acid reactive substances (TBARS) and α-smooth muscle actin (α-SMA) caused by WD. Furthermore, gut microbiota characterized by 16S rRNA sequencing revealed that BA reduced remarkably the ratio of Firmicutes/Bacteroidetes (F/B) and modified gut microbiome. In particular, BA increased the relative abundance of g_Akkermansia and g_Parabacteroides. Taken together, our data demonstrated that BA might ameliorate WD-induced NAFLD by attenuating dyslipidemia and gut microbiome dysbiosis.