Manifestation Of Metabolic Syndrome Research Articles

Altered Mitochondrial Dynamics in Hepatocytes Induces Nonalcoholic Fatty Liver Disease Progression

Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome that affects approximately 25% of adults globally. Although several pharmacological therapies have been reported to improve NAFLD, the therapeutic ranges of the drugs are limited. Mitochondrial dysfunction could be a key factor involved in NAFLD progression. However, the association between mitochondrial dynamics, which involves mitochondrial fission and fusion, and NAFLD development has not been fully characterized to date. Herein, we examined the effects of alterations of mitochondrial dynamics in hepatocytes and liver sinusoidal endothelial cells (LSECs), the most abundant non‐parenchymal cells in the liver, on NAFLD development and hypothesized that rebalancing of mitochondrial dynamics in these cells could attenuate NAFLD progression. Mice were fed a choline‐deficient, L‐amino acid‐defined diet (CDAA) for 1 or 4 weeks to recapitulate human NAFLD development. Malformed mitochondria, such as megamitochondria and mitochondria with deformed cristae, were substantially increased in both, hepatocytes and LSECs, of mice that were fed CDAA diet, and were associated with NAFLD development. In addition, decreased mitochondrial content and increased mitochondrial number, suggesting excessive mitochondrial fission, were induced in hepatocytes, but not in LSECs, after four weeks of CDAA feeding. These unfavorable changes in the mitochondria of hepatocytes, but not of LSECs, were attenuated by mdivi1, a chemical mitochondrial fission inhibitor. Liver inflammation and fibrosis were also attenuated by mdivi1, as assessed by serum biochemical and histochemical analyses. The expression of several inflammatory and fibrogenic genes (Tnfα, Il6, and Col3α1) tended to decrease with mdivi1 treatment. The expression of genes related to mitochondrial biogenesis, fission, fusion, and mitophagy was also significantly reduced by mdivi1 (p<0.05), suggesting rebalanced mitochondrial dynamics. Ultrastructural analyses revealed that endoplasmic reticulum stress and autophagy in hepatocytes were mitigated by mdivi1 administration. Taken together, these findings suggest that excessive mitochondrial fission in hepatocytes induces alterations in mitochondrial dynamics and other organellar injuries, and subsequently, liver inflammation and fibrogenesis. Therefore, rebalancing mitochondrial dynamics in hepatocytes by inhibiting excessive fission is a promising therapeutic strategy for NAFLD.

Comparative evaluation of different types of bariatric surgery

Introduction. The use of bariatric surgery as a treatment for obesity has increased dramatically over the past few years. Because the results in obese patients with type 2 diabetes were so impressive, the International Diabetes Federation recommended considering bariatric surgery as an acceptable treatment option in patients with a BMI of 30-35 kg / m2 when diabetes cannot be adequately controlled with traditional therapies.
 The aim of the study is to compare the results of bariatric surgery in patients with metabolic syndrome according to the dynamics of body mass index and major orexigenic and anorexigenic hormones.
 Material and Methods. The results of surgical treatment of 19 patients with morbid obesity (5 men and 14 women) aged 44 ± 3.26 years with a body mass index ˃40 kg / m2 were evaluated. The control group consisted of 12 patients with normal body mass index and no manifestations of metabolic syndrome.
 Results. Our study also demonstrated the positive effect of LGAE on hormonal parameters with a decrease in ghrelin and leptin. This helped reduce BMI by 10.12% after 6 months. At the same time there is an increase in adiponectin and resistin.
 Conclusions. LGAE in patients with ghrelin-associated obesity is possible as an alternative intervention, given its good tolerability. Or, as the first preparatory stage of comprehensive surgical treatment in obese patients who are not good candidates for standard bariatric surgery.

Meta-Inflammation and De Novo Lipogenesis Markers Are Involved in Metabolic Associated Fatty Liver Disease Progression in BTBR ob/ob Mice.

Metabolic associated fatty liver disease (MAFLD) is a hepatic manifestation of metabolic syndrome and usually associated with obesity and diabetes. Our aim is to characterize the pathophysiological mechanism involved in MAFLD development in Black Tan and brachyuric (BTBR) insulin-resistant mice in combination with leptin deficiency (ob/ob). We studied liver morphology and biochemistry on our diabetic and obese mice model (BTBR ob/ob) as well as a diabetic non-obese control (BTBR + streptozotocin) and non-diabetic control mice (BTBR wild type) from 4–22 weeks. Lipid composition was assessed, and lipid related pathways were studied at transcriptional and protein level. Microvesicular steatosis was evident in BTBR ob/ob from week 6, progressing to macrovesicular in the following weeks. At 12th week, inflammatory clusters, activation of STAT3 and Nrf2 signaling pathways, and hepatocellular ballooning. At 22 weeks, the histopathological features previously observed were maintained and no signs of fibrosis were detected. Lipidomic analysis showed profiles associated with de novo lipogenesis (DNL). BTBR ob/ob mice develop MAFLD profile that resemble pathological features observed in humans, with overactivation of inflammatory response, oxidative stress and DNL signaling pathways. Therefore, BTBR ob/ob mouse is an excellent model for the study of the steatosis to steatohepatitis transition.

Immune-related pathogenesis and therapeutic strategies of nonalcoholic steatohepatitis.

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and has become prevalent in the adult population worldwide, given the ongoing obesity pandemic. NAFLD comprises several hepatic disorders, ranging from fatty liver to nonalcoholic steatohepatitis (NASH), cirrhosis, and carcinoma. Excessive fat accumulation in the liver can induce the development of fatty liver, whereas the progression of fatty liver to NASH involves various complex factors. The crucial difference between fatty liver and NASH is the presence of inflammation and fibrosis, the emergence of which is closely associated with the action of immune cells and immunological factors, such as chemokines and cytokines. Thus, expanding our understanding of immunological mechanisms contributing to NASH pathogenesis will lead to the identification of therapeutic targets and the development of viable therapeutics against NASH.

THE EFFECT OF A PREBIOTIC DIET SUPPLEMENT ON LIVER FAT INFILTRATION AND METABOLIC OSTEOARTHRITIS IN OBESE RATS

Purpose: Diet-induced obesity (DIO) is associated with a range of liver irregularities, non-alcoholic fatty liver disease (NAFLD) being the most prevalent in the economically developed countries. NAFLD is characterized through an excessive accumulation of fat in liver cells with minimal or no alcohol consumption and is considered as the hepatic manifestation of metabolic syndrome. Metabolic osteoarthritis, a subtype of osteoarthritis (OA), shares critical obesity-related characteristics of a fatty liver such as low-grade inflammation and dysbiosis of the gut microbiota.

SGLT2 Inhibitors as the Most Promising Influencers on the Outcome of Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD), the most frequent liver disease in the Western world, is a common hepatic manifestation of metabolic syndrome (MetS). A specific cure has not yet been identified, and its treatment is currently based on risk factor therapy. Given that the initial accumulation of triglycerides in the liver parenchyma, in the presence of inflammatory processes, mitochondrial dysfunction, lipotoxicity, glucotoxicity, and oxidative stress, can evolve into non-alcoholic steatohepatitis (NASH). The main goal is to identify the factors contributing to this evolution because, once established, untreated NASH can progress through fibrosis to cirrhosis and, ultimately, be complicated by hepatocellular carcinoma (HCC). Several drugs have been tested in clinical trials for use as specific therapy for NAFLD; most of them are molecules used to cure type 2 diabetes mellitus (T2DM), which is one of the main risk factors for NAFLD. Among the most studied is pioglitazone, either alone or in combination with vitamin E, glucagon-like peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors. Actually, the most promising category seems to be sodium-glucose cotransporter (SGLT2) inhibitors. Their action is carried out by inhibiting glucose reabsorption in the proximal renal tubule, leading to its increased excretion in urine and decreased levels in plasma. Experimental studies in animal models have suggested that SGLT2 inhibitors may have beneficial modulatory effects on NAFLD/NASH, and several trials in patients have proven their beneficial effects on liver enzymes, BMI, blood lipids, blood glucose, and insulin resistance in NAFLD patients, thus creating strong expectations for their possible use in preventing the evolution of liver damage in these patients. We will review the main pathogenetic mechanisms, diagnostic modalities, and recent therapies of NAFLD, with particular attention to the use of SGLT2 inhibitors.

Association of serum methionine metabolites with non-alcoholic fatty liver disease: a cross-sectional study

Background and projectNon-alcoholic fatty liver disease (NAFLD) is viewed as the hepatic manifestation of metabolic syndrome. Methionine metabolites have been linked to metabolic syndrome and its related diseases. Whether serum methionine metabolites levels are associated with NAFLD remains unclear. The study aimed to assess the association between methionine metabolites and NAFLD.MethodsThis cross-sectional study included a total of 2814 individuals aged 40–75 years old. All participants underwent anthropometric measurements, laboratory tests, dietary assessment and abdominal ultrasonography. Multivariable logistic regression analysis was performed to estimate the association of methionine metabolites with NAFLD.ResultsOverall, 1446 with and 1368 without NAFLD were enrolled in this study. Participants with NAFLD had significantly higher serum S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH) and homocysteine (Hcy) levels, and a lower S-adenosylmethionine/S-adenosylhomocysteine (SAM/SAH) ratio than those without NAFLD (all P < 0.001). After adjusting multiple confounders, odds ratios (95% confidence interval) for quartile 4 versus quartile 1 of SAH, Hcy and SAM/SAH ratio were 1.65 (1.27–2.14), 1.63 (1.26–2.12) and 0.63 (0.49–0.83), respectively (all P for trend < 0.01). In addition, serum SAH, Hcy levels and SAM/SAH ratio were significantly correlated with the degree of hepatic steatosis (all P for trend < 0.001).ConclusionElevated serum SAH, Hcy levels and lower SAM/SAH ratio may be independently associated with the presence of NAFLD in middle-aged and elder Chinese.

Added Fructose in Non-Alcoholic Fatty Liver Disease and in Metabolic Syndrome: A Narrative Review.

Non-alcoholic fatty liver disease (NAFLD) represents the most common chronic liver disease and it is considered the hepatic manifestation of metabolic syndrome (MetS). Diet represents the key element in NAFLD and MetS treatment, but some nutrients could play a role in their pathophysiology. Among these, fructose added to foods via high fructose corn syrup (HFCS) and sucrose might participate in NAFLD and MetS onset and progression. Fructose induces de novo lipogenesis (DNL), endoplasmic reticulum stress and liver inflammation, promoting insulin resistance and dyslipidemia. Fructose also reduces fatty acids oxidation through the overproduction of malonyl CoA, favoring steatosis. Furthermore, recent studies suggest changes in intestinal permeability associated with fructose consumption that contribute to the risk of NAFLD and MetS. Finally, alterations in the hunger–satiety mechanism and in the synthesis of uric acid link the fructose intake to weight gain and hypertension, respectively. However, further studies are needed to better evaluate the causal relationship between fructose and metabolic diseases and to develop new therapeutic and preventive strategies against NAFLD and MetS.

The importance of laboratory parameters of the lipid transport system and adipose tissue hormones in assessing the course of chronic.

The main manifestations of metabolic syndrome (MS) are disorders of carbohydrate and lipid metabolism and their hormonal regulation. The combined nature of metabolic disorders can significantly affect the course and prognosis of CHF in elderly people with metabolic syndrome. To determine the features of the combined effect of metabolic laboratory parameters and biological active factors of adipose tissue in patients with CHF and metabolic syndrome on the course of the disease. A comparison was made between a group of patients with CHF complicated by MS(n=37) and a group of patients with CHF without MS (n=37). The parameters of lipid metabolism (cholesterol CH and lipoproteins LP), the lipid transport system (ApoA1 and ApoB), leptin, adiponectin and resistin and their mutual relations were studied. The ratio of ApoB/ApoAI levels was indicative, which was 0.80±0.32 in patients with CHF without MS, and 1.12±0.46 in patients with CHF with MS (p <0.05). A significant correlation was found between the ratio of ApoB/ApoA1 levels and abdominal obesity (r=0.42, p<0.05), functional class of CHF (r=0.463, p<0.05), LDL-C level (r=0.518, p<0.05), and triglycerides (r=0.476, p<0.05). Also, significant results were obtained for the leptin/adiponectin ratio. For this ratio, 4 ranks were derived depending on the value of the leptin (ng/ml)/adiponectin (mcg/ml) ratio: less than 1 - rank 0 was assigned, with values of the ratio in the range 1 - 3 - rank 1, in the range 3.1 - 6 - rank 2, and above the value 6 - rank 3. Of the 22 patients who had improved CHF at the end of hospitalization, all at the beginning of hospitalization had a rank 0 or 1 ApoB/ApoA1 ratio. Thus, ranking the values of the ratio of ApoB/ApoA1 levels, and especially leptin/adiponectin, can suggest the probability of successful treatment of CHF or the probability of deterioration of the patient's condition, up to a fatal outcome.

Platelets in Non-alcoholic Fatty Liver Disease.

Non alcoholic steatohepatitis (NASH) is the inflammatory reaction of the liver to excessive accumulation of lipids in the hepatocytes. NASH can progress to cirrhosis and hepatocellular carcinoma (HCC). Fatty liver is the hepatic manifestation of metabolic syndrome. A subclinical inflammatory state is present in patients with metabolic alterations like insulin resistance, type-2 diabetes, obesity, hyperlipidemia, and hypertension. Platelets participate in immune cells recruitment and cytokines-induced liver damage. It is hypothesized that lipid toxicity cause accumulation of platelets in the liver, platelet adhesion and activation, which primes the immunoinflammatory reaction and activation of stellate cells. Recent data suggest that antiplatelet drugs may interrupt this cascade and prevent/improve NASH. They may also improve some metabolic alterations. The pathophysiology of inflammatory liver disease and the implication of platelets are discussed in details.

Pathological involvement of apoptotic and inflammatory molecules in cardiovascular remodeling in rats on high fructose diet-induced metabolic syndrome.

Fructose consumption has been linked to manifestation of metabolic syndrome (MS); an emerging epidemic. The current study attempts to demonstrate fructose overconsumption-mediated cardiovascular disease (CVD) remodeling in Wistar rats. Rats were randomly segregated into control (CON) and high fructose diet (FFR) groups and received customized diets for 20weeks. Levels of diabetic, lipid, antioxidant, markers, mRNA levels of inflammatory, apoptotic markers, and histopathological changes were assessed in excised hearts of both groups. Significant increase in uric acid, pro-oxidants diabetic, lipid, inflammatory markers, cytosolic cytochrome C, nuclear NF-кB-p65, and decrease in antioxidants was observed in FFR group. Abnormal myocardial architecture was observed in the FFR group along with elevated mRNA levels of inflammatory, apoptotic markers, and MMP-9, -2. The outcomes of the study are suggestive of role of aforementioned molecules in high fructose intake-mediated pathological deterioration of heart and development of MS-associated CVD progression. PRACTICAL APPLICATIONS: Excessive fructose consumption in the form of high fructose corn syrup, sugary drinks, and commonly available fast foods has been shown to be linked with many diseases such as liver malfunction, metabolic syndrome diabetes, and cardiovascular diseases. However, delineated pathways and clear mechanisms and their role in cardiovascular remodeling due to excessive fructose consumption are yet to be established. The present study establishes the deleterious effects of foods with high sugar content on progression toward metabolic syndrome and cardiovascular remodeling. It further investigates the role of different pathways involved in the development of high fructose-induced diet-induced metabolic syndrome, and thereby leading to harmful effects on the hearts of rats consuming high fructose diet leading to cardiovascular in Wistar rats. The study suggests the role of immunomodulation and oxidative stress in the remodeling of cardiac muscles and in turn progression toward metabolic syndrome and cardiovascular remodeling. The study, therefore, throws light on the deleterious effects of consumption of foods and easily available fast foods on progression toward numerous non-communicable diseases.

Metabolic syndrome is associated with poor response to rifaximin in minimal hepatic encephalopathy

Patients with cirrhosis may show minimal hepatic encephalopathy (MHE), for which rifaximin is effective. Metabolic syndrome may be associated with cognitive impairment. Our aims were to evaluate the influence of metabolic syndrome features on response to rifaximin for neurological and inflammatory alterations in MHE. A prospective cohort study was conducted in 63 cirrhotic patients and 30 controls from two tertiary centres recruited between 2015 and 2019. Metabolic syndrome was defined according to the Adult Treatment Panel-III. Patients were classified into 31 without and 32 with MHE according to the Psychometric Hepatic Encephalopathy Score (PHES). All participants performed specific psychometric tests, and inflammatory parameters were studied. Patients with MHE received rifaximin (400 mg/8 h). Response was evaluated by PHES at 3 and 6 months. Response according to metabolic syndrome manifestations was compared. The response rate was 66%. Older age (p = 0.012) and all metabolic syndrome diseases (p < 0.05) were associated with non-response, plus an increase in risk as the number of manifestations rose (p < 0.001). Patients with metabolic manifestations exhibited worse processing speed (p = 0.011), working memory (p = 0.005), visual coordination (p = 0.013) and lower proportion of activated CD4+ lymphocytes (p = 0.039) at baseline, as well as worse concentration (p = 0.030), bimanual coordination (p = 0.004) and higher levels of intermediate monocytes (p = 0.026), CX3CL1 (p < 0.05), IL-17 (p = 0.022), AHR (p = 0.010) and IgG (p < 0.05) at 3 and/or 6 months of rifaximin. Patients with clinical signs of metabolic syndrome have poor response to rifaximin for MHE, with a higher proportion of neurological alterations associated with a pro-inflammatory environment.

Non-Alcoholic Fatty Liver Disease and Risk of Macro- and Microvascular Complications in Patients with Type 2 Diabetes.

Non-alcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome. To date, NAFLD is the most frequent chronic liver disease seen day by day in clinical practice across most high-income countries, affecting nearly 25–30% of adults in the general population and up to 70% of patients with T2DM. Over the last few decades, it clearly emerged that NAFLD is a “multisystemic disease” and that the leading cause of death among patients with NAFLD is cardiovascular disease (CVD). Indeed, several observational studies and some meta-analyses have documented that NAFLD, especially its advanced forms, is strongly associated with fatal and non-fatal cardiovascular events, as well as with specific cardiac complications, including sub-clinical myocardial alteration and dysfunction, heart valve diseases and cardiac arrhythmias. Importantly, across various studies, these associations remained significant after adjustment for established cardiovascular risk factors and other confounders. Additionally, several observational studies and some meta-analyses have also reported that NAFLD is independently associated with specific microvascular conditions, such as chronic kidney disease and distal or autonomic neuropathy. Conversely, data regarding a potential association between NAFLD and retinopathy are scarce and often conflicting. This narrative review will describe the current evidence about the association between NAFLD and the risk of macro- and microvascular manifestations of CVD, especially in patients with T2DM. We will also briefly discuss the biological mechanisms underpinning the association between NAFLD and its advanced forms and macro- and microvascular CVD.

Copper-catalyzed dicarbonyl stress in NAFLD mice: protective effects of Oleuropein treatment on liver damage

BackgroundNonalcoholic fatty liver disease (NAFLD) or more appropriately, metabolic associated fatty liver disease (MAFLD), is the hepatic manifestation of metabolic syndrome. An imbalance of copper homeostasis has been described in the progression of NAFLD/MAFLD toward NASH/MASH. We were interested in understanding whether the chelating activity of Oleuropein (Ole) was able to improve the copper accumulation and the related pro-oxidant and glycative damage in the liver of mice fed HFD.MethodsTwelve C57BL/6J mice fed normal diet (ND) or high-fat diet (HFD) for 16 weeks and then thirty two female and male mice fed ND or HFD for 8 weeks adding Ole for the following 8 weeks were studied.ResultsAltered expression of copper-trafficking genes and proteins (CTR1, CTR2, ATP7B, COX17, CCS, and ATOX1) induced imbalance of copper homeostasis combined with an increase in dicarbonyl stress in the liver of HFD fed mice. Interestingly enough, glyoxalase system was improved by Ole administration and the Ole related protective effects differ in the two sexes of mice.ConclusionsOur study highlights the role of the dicarbonyl stress in the pathogenesis of NAFLD and suggests Ole as a natural copper chelator to prevent the liver damage induced by methyglyoxal pathway derangement.

Effects of glycine on metabolic syndrome components: a review.

Glycine is the simplest and major amino acid in humans. It is mainly generated in the liver and kidney and is used to produce collagen, creatine, glucose and purine. It is also involved in immune function, anti-inflammatory processes and anti-oxidation reactions. Here, we reviewed the current evidence supporting the role of glycine in the development and treatment of metabolic syndrome components. We searched Scopus, PubMed and EMBASE databases for papers concerning glycine and metabolic syndrome. Available evidence shows that the amount of glycine synthesized in vivo is insufficient to meet metabolic demands in these species. Plasma glycine levels are lower in subjects with metabolic syndrome than in healthy individuals. Interventions such as lifestyle modification, exercise, weight loss, or drugs that improve manifestations of metabolic syndrome remarkably increase circulating glycine concentrations. Glycine supplementation improves various components of metabolic syndrome including diabetes, obesity, hyperlipidemia and hypertension. In the future, the use of glycine may have a significant clinical impact on the treatment of patients with metabolic syndrome.

A comprehensive review on phytochemicals for fatty liver: are they potential adjuvants?

Non-alcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome and, as such, is associated with obesity. With the current and growing epidemic of obesity, NAFLD is already considered the most common liver disease in the world. Currently, there is no official treatment for the disease besides weight loss. Although there are a few synthetic drugs currently being studied, there is also an abundance of herbal products that could also be used for treatment. With the World Health Organization (WHO) traditional medicine strategy (2014-2023) in mind, this review aims to analyze the mechanisms of action of some of these herbal products, as well as evaluate toxicity and herb-drug interactions available in literature.

The combination of berberine and evodiamine ameliorates high-fat diet-induced non-alcoholic fatty liver disease associated with modulation of gut microbiota in rats.

Nonalcoholic fatty liver disease (NAFLD) is considered to be a manifestation of hepatic metabolic syndrome. Some studies on the pathogenesis of NAFLD by targeting gut microbiota have attracted wide attention. Previous studies have demonstrated the positive effects of berberine and evodiamine on metabolic diseases and gut microbiota dysbiosis. However, it is not known whether the combination of berberine and evodiamine (BE) can prevent the development of high-fat diet (HFD)-induced NAFLD. Therefore, we aimed to explore the protective effects of BE on the development of HFD-induced NAFLD from the perspective of the gut microbiota. Gut microbiota profiles were established by high throughput sequencing of the bacterial 16S ribosomal RNA gene. The effects of BE on liver and intestinal tissue, intestinal barrier integrity, and hepatic inflammation were also investigated. The results showed that the abundance and diversity of gut microbiota were enriched by BE treatment, with an increase in beneficial bacteria, such as Lactobacillus, Ruminococcus, and Prevotella, and a decrease in pathogenic bacteria such as Fusobacterium and Lachnospira. In addition, BE effectively improved liver fat accumulation and tissue damage, inhibited the apoptosis of intestinal epithelial cells, increased the contents of intestinal tight junction proteins, and decreased the expression of pro-inflammatory factors. Consequently, BE treatment could be an effective and alternative strategy for alleviating NAFLD by modulating gut microbiota and safeguarding the intestinal barrier.

Association of NAFLD with cardiovascular disease and all-cause mortality: a large-scale prospective cohort study based on UK Biobank.

Objective:Nonalcoholic fatty liver disease (NAFLD) is considered as the hepatic manifestation of metabolic syndrome, sharing the similar cardiometabolic risk factors with cardiovascular disease (CVD). Whether NAFLD by itself is associated with increased cardiovascular events and death remain an issue to debate. This study aimed to further investigate the association between NAFLD and adverse CVD outcomes.Methods:Participants were followed up until the end of 2020 in current analysis. NAFLD is defined using fatty liver index (FLI). Cox proportional hazard model was used to analyze the association between NAFLD and all-cause mortality, major adverse cardiovascular events (MACEs), CVD mortality, fatal/nonfatal acute myocardial infarction (AMI), and fatal/nonfatal stroke. C-index was calculated to evaluate the model enhancement when adding NAFLD factor.Results:After screening the data of 502,492 participants in the original cohort, 215,245 eligible participants were included in this study for MACEs outcome. Compared with non-NAFLD participants, the multivariable adjusted hazard ratios of NAFLD group was 1.25 (1.14–1.36) for MACEs; 1.14 (1.08–1.20) for all-cause mortality; 1.61(1.42–1.82) for CVD mortality; 1.58(1.19–2.11) for AMI mortality; and 1.18 (0.85–1.64) for stroke mortality. When adding FLI, C-index of NAFLD model improved for all-cause mortality, MACEs, and CVD mortality compared with that in the traditional CVD risk factor model.Conclusion:NAFLD is an independent risk factor for all-cause mortality and adverse CVD outcomes. Based on the traditional CVD risk factor model, additionally screening NAFLD could improve the prediction efficiency for adverse CVD outcomes.

Prevalence of Coronary Artery Disease in Patients Undergoing Liver Transplantation for NASH

Background and Aim: Non Alcoholic Fatty Liver Disease (NAFLD) is the hepatic manifestation of metabolic syndrome. Patients with NALFD also have increased endothelial dysfunction, coronary artery calcification and increased arterial stiffness which risks higher occurrence of coronary events.

3082 – NONALCOHOLIC STEATOHEPATITIS PROMOTES EMERGENCY MYELOPOIESIS AND IMMUNE EFFECTOR DYSFUNCTION

Neutrophils and macrophages act as sentinels and help protect against injury and infection. Emergency myelopoiesis is triggered during this process and increases production of myeloid cells from hematopoietic stem and progenitor cells (HSPCs). This process is largely studied under acute stressors such as infection, but the impact of organ-specific inflammation on emergency myelopoiesis is poorly explored. Metabolic disorders induce metainflammation, a low-grade systemic chronic inflammation that results in elevated myeloid cells in circulation. The link of metainflammation to emergency myelopoiesis is not understood. We examined emergency myelopoiesis and immune cell function in a zebrafish model for Nonalcoholic steatohepatitis (NASH), an aggressive, pro-inflammatory hepatic manifestation of metabolic syndrome. To induce NASH, zebrafish larvae were fed a high-cholesterol diet for 1 week leading to liver steatohepatitis and chronic systemic inflammation. We detected increased proliferation of hematopoietic progenitors, as evidenced by increased 5-ethynyl-2’deoxyuridine (5-EdU) incorporation in hematopoietic tissues. Consistent with these findings, cd41:GFP-positive HSPCs as well as the total number of neutrophils and macrophages were increased in NASH larvae when compared to larvae fed with normal diet. In addition, neutrophils from NASH larvae displayed a hyperactive and dysfunctional response, as evidenced by exacerbated recruitment of lyz:H2B-mCherry-positive neutrophils to a tailfin injury. Neutrophils in NASH zebrafish also had increased speed, delayed resolution, and increased neutrophil reactive oxygen species production at the injury site. These data suggest that metabolic disorders, such as NASH, can promote emergency myelopoiesis and immune effector dysfunction leading to a host of inflammatory deregulation in these individuals. Neutrophils and macrophages act as sentinels and help protect against injury and infection. Emergency myelopoiesis is triggered during this process and increases production of myeloid cells from hematopoietic stem and progenitor cells (HSPCs). This process is largely studied under acute stressors such as infection, but the impact of organ-specific inflammation on emergency myelopoiesis is poorly explored. Metabolic disorders induce metainflammation, a low-grade systemic chronic inflammation that results in elevated myeloid cells in circulation. The link of metainflammation to emergency myelopoiesis is not understood. We examined emergency myelopoiesis and immune cell function in a zebrafish model for Nonalcoholic steatohepatitis (NASH), an aggressive, pro-inflammatory hepatic manifestation of metabolic syndrome. To induce NASH, zebrafish larvae were fed a high-cholesterol diet for 1 week leading to liver steatohepatitis and chronic systemic inflammation. We detected increased proliferation of hematopoietic progenitors, as evidenced by increased 5-ethynyl-2’deoxyuridine (5-EdU) incorporation in hematopoietic tissues. Consistent with these findings, cd41:GFP-positive HSPCs as well as the total number of neutrophils and macrophages were increased in NASH larvae when compared to larvae fed with normal diet. In addition, neutrophils from NASH larvae displayed a hyperactive and dysfunctional response, as evidenced by exacerbated recruitment of lyz:H2B-mCherry-positive neutrophils to a tailfin injury. Neutrophils in NASH zebrafish also had increased speed, delayed resolution, and increased neutrophil reactive oxygen species production at the injury site. These data suggest that metabolic disorders, such as NASH, can promote emergency myelopoiesis and immune effector dysfunction leading to a host of inflammatory deregulation in these individuals.