Milk fat globule epidermal growth factor 8 alleviates liver injury in severe acute pancreatitis by restoring autophagy flux and inhibiting ferroptosis in hepatocytes

BACKGROUND Liver injury is common in severe acute pancreatitis(SAP).Excessive autophagy often leads to an imbalance of homeostasis in hepatocytes,which induces lipid peroxidation and mitochondrial iron deposition and ultimately leads to ferroptosis.Our previous study found that milk fat globule epidermal growth factor 8(MFG-E8)alleviates acinar cell damage during SAP via binding toαvβ3/5 integrins.MFG-E8 also seems to mitigate pancreatic fibrosis via inhibiting chaperone-mediated autophagy.AIM To speculate whether MFG-E8 could also alleviate SAP induced liver injury by restoring the abnormal autophagy flux.METHODS SAP was induced in mice by 2 hly intraperitoneal injections of 4.0 g/kg L-arginine or 7 hly injections of 50μg/kg cerulein plus lipopolysaccharide.mfge8-knockout mice were used to study the effect of MFG-E8 deficiency on SAPinduced liver injury.Cilengitide,a specificαvβ3/5 integrin inhibitor,was used to investigate the possible mechanism of MFG-E8.RESULTS The results showed that MFG-E8 deficiency aggravated SAP-induced liver injury in mice,enhanced autophagy flux in hepatocyte,and worsened the degree of ferroptosis.Exogenous MFG-E8 reduced SAP-induced liver injury in a dose-dependent manner.Mechanistically,MFG-E8 mitigated excessive autophagy and inhibited ferroptosis in liver cells.Cilengitide abolished MFG-E8’s beneficial effects in SAP-induced liver injury.CONCLUSION MFG-E8 acts as an endogenous protective mediator in SAP-induced liver injury.MFG-E8 alleviates the excessive autophagy and inhibits ferroptosis in hepatocytes by binding to integrinαVβ3/5.

Immune and metabolic cross-links in the pathogenesis of comorbid non-alcoholic fatty liver disease

In recent years,there has been a steady growth of interest in non-alcoholic fatty liver disease(NAFLD),which is associated with negative epidemiological data on the prevalence of the disease and its clinical significance.NAFLD is closely related to the metabolic syndrome and these relationships are the subject of active research.A growing body of evidence shows cross-linkages between metabolic abnormalities and the innate immune system in the development and progression of NAFLD.These links are bidirectional and largely still unclear,but a better understanding of them will improve the quality of diagnosis and management of patients.In addition,lipid metabolic disorders and the innate immune system link NAFLD with other diseases,such as atherosclerosis,which is of great clinical importance.

Non-alcoholic fatty liver disease:Immunological mechanisms and current treatments

Non-alcoholic fatty liver disease(NAFLD)causes significant global disease burden and is a leading cause of mortality.NAFLD induces a myriad of aberrant changes in hepatocytes at both the cellular and molecular level.Although the disease spectrum of NAFLD is widely recognised,the precise triggers for disease progression are still to be fully elucidated.Furthermore,the propagation to cirrhosis is poorly understood.Whilst some progress in terms of treatment options have been explored,an incomplete understanding of the hepatic cellular and molecular alterations limits their clinical utility.We have therefore reviewed some of the key pathways responsible for the pathogenesis of NAFLD such as innate and adaptative immunity,lipotoxicity and fibrogenesis,and highlighted current trials and treatment options for NAFLD patients.

Effect of replacement of soybean oil by Hermetia illucens fat on performance,digestibility,cecal microbiome,liver transcriptome and liver and plasma lipidomes of broilers

Background In contrast to protein-rich insect meal,the feed potential of insect fat is generally less explored and knowledge about the suitability of insect fat as a fat source specifically in broiler diets is still limited.In view of this,the present study aimed to comprehensively investigate the effect of partial(50%) and complete replacement of soybean oil with insect fat from Hermetia illucens(HI) larvae in broiler diets on performance,fat digestibility,cecal microbiome,liver transcriptome and liver and plasma lipidomes.Thus,100 male,1-day-old Cobb 500 broilers were randomly assigned to three groups and fed three different diets with either 0(group HI-0,n cens(HI) larvae fat for 35 d.= 30),2.5%(group HI-2.5,n %(HI-5.0,n = 35) or 5.0= 35) Hermetia illuResults Body weight gain,final body weight,feed intake,and feed:gain ratio during the whole period and apparent ileal digestibility coefficient for ether extract were not different between groups.Cecal microbial diversity did not differ between groups and taxonomic analysis revealed differences in the abundance of only four low-abundance bacterial taxa among groups;the abundances of phylum Actinobacteriota,class Coriobacteriia,order Coriobacteriales and family Eggerthellaceae were lower in group HI-5.0 compared to group HI-2.5(P < 0.05).Concentrations of total and individual short-chain fatty acids in the cecal digesta were not different between the three groups.Liver transcriptomics revealed a total of 55 and 25 transcripts to be differentially expressed between groups HI-5.0 vs.HI-0 and groups HI-2.5 vs.HI-0,respectively(P < 0.05).The concentrations of most lipid classes,with the exception of phosphatidylethanolamine,phosphatidylglycerol and lysophosphatidylcholine in the liver and cholesterylester and ceramide in plasma(P < 0.05),and of the sum of all lipid classes were not different between groups.Conclusions Partial and complete replacement of soybean oil with HI larvae fat in broiler diets had no effect on growth performance and only modest,but no adverse effects on the cecal microbiome and the metabolic health of broilers.This suggests that HI larvae fat can be used as an alternative fat source in broiler diets,thereby,making broiler production more sustainable.

Assessing the impact of concurrent high-fructose and highsaturated fat diets on pediatric metabolic syndrome:A review

High-saturated fat(HF)or high-fructose(HFr)consumption in children predispose them to metabolic syndrome(MetS).In rodent models of MetS,diets containing individually HF or HFr lead to a variable degree of MetS.Nevertheless,simultaneous intake of HF plus HFr have synergistic effects,worsening MetS outcomes.In children,the effects of HF or HFr intake usually have been addressed individually.Therefore,we have reviewed the outcomes of HF or HFr diets in children,and we compare them with the effects reported in rodents.In humans,HFr intake causes increased lipogenesis,hypertriglyceridemia,obesity and insulin resistance.On the other hand,HF diets promote low grade-inflammation,obesity,insulin resistance.Despite the deleterious effects of simultaneous HF plus HFr intake on MetS development in rodents,there is little information about the combined effects of HF plus HFr intake in children.The aim of this review is to warn about this issue,as individually addressing the effects produced by HF or HFr may underestimate the severity of the outcomes of Western diet intake in the pediatric population.We consider that this is an alarming issue that needs to be assessed,as the simultaneous intake of HF plus HFr is common on fast food menus.

Non-alcoholic fatty liver disease and obesity: Biochemical, metabolic and clinical presentations

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. Presentation of the disease ranges from simple steatosis to non-alcoholic steatohepatitis (NASH). NAFLD is a hepatic manifestation of metabolic syndrome that includes central abdominal obesity along with other components. Up to 80% of patients with NAFLD are obese, defined as a body mass index (BMI) > 30 kg/m2. However, the distribution of fat tissue plays a greater role in insulin resistance than the BMI. The large amount of visceral adipose tissue (VAT) in morbidly obese (BMI > 40 kg/m2) individuals contributes to a high prevalence of NAFLD. Free fatty acids derived from VAT tissue, as well as from dietary sources and de novo lipogenesis, are released to the portal venous system. Excess free fatty acids and chronic low-grade inflammation from VAT are considered to be two of the most important factors contributing to liver injury progression in NAFLD. In addition, secretion of adipokines from VAT as well as lipid accumulation in the liver further promotes inflammation through nuclear factor kappa B signaling pathways, which are also activated by free fatty acids, and contribute to insulin resistance. Most NAFLD patients are asymptomatic on clinical presentation, even though some may present with fatigue, dyspepsia, dull pain in the liver and hepatosplenomegaly. Treatment for NAFLD and NASH involves weight reduction through lifestyle modifications, anti-obesity medication and bariatric surgery. This article reviews the available information on the biochemical and metabolic phenotypes associated with obesity and fatty liver disease. The relative contribution of visceral and liver fat to insulin resistance is discussed, and recommendations for clinical evaluation of affected individuals is provided.

What is the role of adiponectin in obesity related non-alcoholic fatty liver disease?

Non-alcoholic fatty liver disease (NAFLD) is recognized as the most common type of chronic liver disease in Western countries.Insulin resistance is a key factor in the pathogenesis of NAFLD,the latter being considered as the hepatic component of insulin resistance or obesity.Adiponectin is the most abundant adipose-specific adipokine.There is evidence that adiponectin decreases hepatic and systematic insulin resistance,and attenuates liver inflammation and fibrosis.Adiponectin generally predicts steatosis grade and the severity of NAFLD;however,to what extent this is a direct effect or related to the presence of more severe insulin resistance or obesity remains to be addressed.Although there is no proven pharmacotherapy for the treatment of NAFLD,recent therapeutic strategies have focused on the indirect upregulation of adiponectin through the administration of various therapeutic agents and/or lifestyle modifications.In this adiponectin-focused review,the pathogenetic role and the potential therapeutic benefits of adiponectin in NAFLD are analyzed systematically.

Effectiveness of exercise in hepatic fat mobilization in nonalcoholic fatty liver disease: Systematic review

AIM: To investigate the efficacy of exercise interventions on hepatic fat mobilization in non-alcoholic fatty liver disease(NAFLD) patients.METHODS: Ovid-Medline, Pub Med, EMBASE and Cochrane database were searched for randomized trials and prospective cohort studies in adults aged ≥ 18 which investigated the effects of at least 8 wk of exercise only or combination with diet on NAFLD from 2010 to 2016. The search terms used to identify articles, in which exercise was clearly described by type, duration, intensity and frequency were: "NASH", "NAFLD", "nonalcoholic steatohepatitis", "non-alcoholic fatty liver disease", "fat", "steatosis", "diet", "exercise", "MR spectroscopy" and "liver biopsy". NAFLD diagnosis, as well as the outcome measures, was confirmed by either hydrogen-magnetic resonance spectroscopy(H-MRS) or biopsy. Trials that included dietary interventions along with exercise were accepted if they met all criteria. RESULTS: Eight studies met selection criteria(6 with exercise only, 2 with diet and exercise with a total of 433 adult participants). Training interventions ranged between 8 and 48 wk in duration with a prescribed exercise frequency of 3 to 7 d per week, at intensities between 45% and 75% of VO2 peak. The most commonly used imaging modality was H-MRS and one study utilized biopsy. The effect of intervention on fat mobilization was 30.2% in the exercise only group and 49.8% in diet and exercise group. There was no difference between aerobic and resistance exercise intervention, although only one study compared thetwo interventions. The beneficial effects of exercise on intrahepatic triglyceride(IHTG) were seen even in the absence of significant weight loss. Although combining an exercise program with dietary interventions augmented the reduction in IHTG, as well as improved measures of glucose control and/or insulin sensitivity, exercise only significantly decreased hepatic lipid contents.CONCLUSION: Prescribed exercise in subjects with NAFLD reduces IHTG independent of dietary intervention. Diet and exercise was more effective than exercise alone in reducing IHTG.

Freeze-dried Si-Ni-San powder can ameliorate high fat diet-induced non-alcoholic fatty liver disease

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is a common chronic liver disease worldwide.However,to date,there is no ideal therapy for this disease.AIM To study the effects of Si-Ni-San freeze-dried powder on high fat diet-induced NAFLD in mice.METHODS Twenty-four male C57BL/6 mice were randomized into three groups of eight.The control group(CON)was allowed ad libitum access to a normal chow diet.The high fat diet group(FAT)and Si-Ni-San group(SNS)were allowed ad libitum access to a high fat diet.The SNS group was intragastrically administered Si-Ni-San freeze-dried powder(5.0 g/kg)once daily,and the CON and FAT groups were intragastrically administered distilled water.After 12 wk,body weight,liver index,visceral fat index,serum alanine aminotransferase(ALT),portal lipopoly-saccharide(LPS),liver tumor necrosis factor(TNF)-αand liver triglycerides were measured.Intestinal microbiota were analyzed using a 16S r DNA sequencing technique.RESULTS Compared with the FAT group,the SNS group exhibited decreased body weight,liver index,visceral fat index,serum ALT,portal LPS,liver TNF-αand liver triglycerides(P<0.05).Intestinal microbiota analysis showed that the SNS group had different bacterial composition and function compared with the FAT group.In particular,Oscillospira genus was a bacterial biomarker of SNS group samples.CONCLUSION The beneficial effects of Si-Ni-San freeze-dried powder on high fat diet-induced NAFLD in mice may be associated with its anti-inflammatory and changing intestinal microbiota effects.

Pancreatic fat and β-cell function in overweight/obese children with nonalcoholic fatty liver disease

AIM: To analyze the associations of pancreatic fat with other fat depots and β-cell function in pediatric nonalcoholic fatty liver disease(NAFLD).METHODS: We examined 158 overweight/obese children and adolescents, 80 with NAFLD [hepatic fat fraction(HFF) ≥ 5%] and 78 without fatty liver. Visceral adipose tissue(VAT), pancreatic fat fraction(PFF) and HFF were determined by magnetic resonance imaging. Estimates of insulin sensitivity were calculated using the homeostasis model assessment of insulin resistance(HOMA-IR), defined by fasting insulin and fasting glucose and whole-body insulin sensitivity index(WBISI), based on mean values of insulin and glucose obtained from oral glucose tolerance test and the corresponding fasting values. Patients were considered to have prediabetes if they had either:(1) impaired fasting glucose, defined as a fasting glucose level ≥ 100 mg/d L to < 126 mg/d L;(2) impaired glucose tolerance, defined as a 2 h glucose concentration between ≥ 140 mg/d L and < 200 mg/d L; or(3) hemoglobin A1 c value of ≥ 5.7% to < 6.5%.RESULTS: PFF was significantly higher in NAFLD patients compared with subjects without liver involvement. PFF was significantly associated with HFF and VAT, as well as fasting insulin, C peptide, HOMA-IR, and WBISI. The association between PFF and HFF was no longer significant after adjusting for age, gender, Tanner stage, body mass index(BMI)-SD score, and VAT. In multiple regression analysis withWBISI or HOMA-IR as the dependent variables, against the covariates age, gender, Tanner stage, BMI-SD score, VAT, PFF, and HFF, the only variable significantly associated with WBISI(standardized coefficient B,-0.398; P = 0.001) as well as HOMA-IR(0.353; P = 0.003) was HFF. Children with prediabetes had higher PFF and HFF than those without. PFF and HFF were significantly associated with prediabetes after adjustment for clinical variables. When all fat depots where included in the same model, only HFF remained significantly associated with prediabetes(OR = 3.38; 95%CI: 1.10-10.4; P = 0.034).CONCLUSION: In overweight/obese children with NAFLD, pancreatic fat is increased compared with those without liver involvement. However, only liver fat is independently related to prediabetes.

Effects of glucagon-like peptide-1 receptor agonists on non-alcoholic fatty liver disease and inflammation

Glucagon-like peptide1 (GLP-1) is secreted from Langerhans cells in response to oral nutrient intake. Glucagon- like peptide-1 receptor agonists (GLP-1RAs) are a new class of incretin-based anti-diabetic drugs. They function to stimulate insulin secretion while suppressing glucagon secretion. GLP-1-based therapies are now well established in the management of type 2 diabetes mellitus (T2DM), and recent literature has suggested potential applications of these drugs in the treatment of obesity and for protection against cardiovascular and neurological diseases. As we know, along with change in lifestyles, the prevalence of non-alcoholic fatty liver disease (NAFLD) in China is rising more than that of viral hepatitis and alcoholic fatty liver disease, and NAFLD has become the most common chronic liver disease in recent years. Recent studies further suggest that GLP-1RAs can reduce transaminase levels to improve NAFLD by improving blood lipid levels, cutting down the fat content to promote fat redistribution, directly decreasing fatty degeneration of the liver, reducing the degree of liver fibrosis and improving inflammation. This review shows the NAFLD-associated effects of GLP-1RAs in animal models and in patients with T2DM or obesity who are participants in clinical trials. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

Anthropometric indicators of visceral adiposity as predictors of non-alcoholic fatty liver disease: A review

The objective was to critically analyze studies that evaluated the predictive capacity of indicators of visceral adiposity in non-alcoholic fatty liver disease(NAFLD). The bibliographic research was carried out using the electronic database PubMed, LILACS and SciELO, references of selected articles. Although we found few studies, they have already used several indicators of visceral adiposity as waist circumference, waist-to-hip ratio, waist-to-height ratio, Lipid accumulation product, Body Shape Index, Body Roundness Index and most them were good predictors of NAFLD. Thus, the anthropometric indicators may contribute for the diagnosis of NAFLD in a simple, low-cost and noninvasive way, allowing early therapeutic measures to prevent the evolution to non-alcoholic steatohepatitis.

mi R-192-5p regulates lipid synthesis in non-alcoholic fatty liver disease through SCD-1

AIM To evaluate the levels of mi R-192-5 p in non-alcoholic fatty liver disease(NAFLD) models and demonstrate the role of mi R-192-5 p in lipid accumulation. METHODS Thirty Sprague Dawley rats were randomly divided into three groups, which were given a standard diet, a high-fat diet(HFD), and an HFD with injection of liraglutide. At the end of 16 weeks, hepatic mi R-192-5 p and stearoyl-Co A desaturase 1(SCD-1) levels were measured. Mi R-192-5 p mimic and inhibitor and SCD-1 si RNA were transfected into Huh7 cells exposed to palmitic acid(PA). Lipid accumulation was evaluated by oil red O staining and triglyceride assays. Direct interaction was validated by dual-luciferase reporter gene assays.RESULTS The HFD rats showed a 0.46-fold decrease and a 3.5-fold increase in hepatic mi R-192-5 p and SCD-1 protein levels compared with controls, respectively, which could be reversed after disease remission by liraglutide injection(P < 0.01). The Huh7 cells exposed to PA also showed down-regulation and up-regulation of mi R-192-5 p and SCD-1 protein levels, respectively(P < 0.01). Transfection with mi R-192-5 p mimic and inhibitor in Huh7 cells induced dramatic repression and promotion of SCD-1 protein levels, respectively(P < 0.01). Luciferase activity was suppressed and enhanced by mi R-192-5 p mimic and inhibitor, respectively, in wild-type SCD-1(P < 0.01) but not in mutant SCD-1. Mi R-192-5 p overexpression reduced lipid accumulation significantly in PA-treated Huh7 cells, and SCD-1 si RNA transfection abrogated the lipid deposition aggravated by mi R-192-5 p inhibitor(P < 0.01).CONCLUSION This study demonstrates that mi R-192-5 p has a negative regulatory role in lipid synthesis, which is mediated through its direct regulation of SCD-1.

Helicobacter pylori infection is not associated with nonalcoholic fatty liver disease

AIM: To determine whether Helicobacter pylori (H. pylori) infection confers a higher risk of Nonalcoholic fatty liver disease (NAFLD).METHODS: Healthy people who underwent health screening were analyzed retrospectively. Inclusion criteria were age ≥ 20 years, history of H. pylori infection, and recorded insulin level. Participants were classified as H. pylori positive or negative according to 13C urea breath tests. NAFLD was defined using the hepatic steatosis index (HSI) and NAFLD liver fat score (NAFLD-LFS). Those with an HSI > 36 or NAFLD-LFS > -0.640 were considered to have NAFLD. Multivariable logistic regression was performed to identify risk factors for NAFLD.RESULTS: Three thousand six hundred and sixty-three people were analyzed and 1636 (44.7%) were H. pylori positive. H. pylori infection was associated with older age, male gender, hypertension, higher body mass index, and a dyslipidemic profile. HSI differed significantly between H. pylori positive and negative subjects (median 33.2, interquartile range (IQR) 30.0-36.2 for H. pylori-positive vs median 32.6, IQR 29.8-36.0 for negative participants, P = 0.005), but NAFLD-LSF did not [median -1.7, IQR -2.4 - -0.7 vs median -1.8, IQR -2.4-(-0.7), respectively, P = 0.122]. The percentage of people with NAFLD did not differ between infected and uninfected groups: HIS, 26.9% vs 27.1%, P = 0.173; NAFLD-LFS, 23.5% vs 23.1%, P = 0.778. H. pylori infection was not a risk factor, but C-reactive protein concentration and smoking were significant risk factors for NAFLD.CONCLUSION: H. pylori infection is not a risk factor for NAFLD as indicated by HSI or NAFLD-LFS. Prospective, large-scale studies involving liver biopsies should be considered.

Nonalcoholic fatty liver disease and vascular disease:State-of-the-art

Nonalcoholic fatty liver disease(NAFLD), the most common of chronic liver disease in Western Country, is closely related to insulin resistance and oxidative stress and includes a wide spectrum of liver diseases ranging from steatosis alone, usually a benign and non-progressive condition, to nonalcoholic steatohepatitis(NASH), which may progress to liver fibrosis and cirrhosis. NAFLD is considered the hepatic manifestation of the metabolic syndrome with which shares several characteristics, however recent data suggest that NAFLD is linked to increased cardiovascular risk independently of the broad spectrum of risk factors of metabolic syndrome. Accumulating evidence suggests that the clinical burden of NAFLD is not restricted to liver-related morbidity and mortality, with the majority of deaths in NAFLD patients related to cardiovascular disease and cancer and not to the progression of liver disease. Retrospective and prospective studies provide evidence of a strong association between NAFLD and subclinical manifestation of atherosclerosis(increased intima-media thickness, endothelial dysfunction, arterial stiffness, impaired left ventricular function and coronary calcification). A general agreement emerging from these studies indicates that patients with NASH are at higher risk of cardiovascular diseases than those with simple steatosis, emphasizing the role of chronic inflammation in the pathogenesis of atherosclerosis of these patients. It is very likely that the different mechanisms involved in the pathogenesis of atherosclerosis in patients with NAFLD have a different relevance in the patients according to individual genetic background. In conclusion, in the presence of NAFLD patients should undergo a complete cardiovascular evaluation to prevent future atherosclerotic complications. Specific lifestyle modification and aggressive pharmaceutical modification will not only reduce the progression of liver disease, but also reduce morbidity for cardiovascular disease improving overall prognosis and survival.

Iron deposition and fat accumulation in dimethylnitrosamine-induced liver fibrosis in rat

AIM： To investigate if iron deposition and fat accumulation in the liver play a pathogenetic role in dimethylnitrosamine （DMN）-induced liver fibrosis in rat.METHODS： Thirty rats were treated with DMN at does consecutive days of 10 μL/kg daily, i.p., for 3 consecutive day each week for 4 wk. Rats （n = 30） were sacrificed on the first day （model group A） and 21st d （model group B） after cessation of DMN injection. The control group （n = 10） received an equivalent amount of saline. Liver tissues were stained with hematoxylin ＆ eosin （HE） and Masson and Prussian blue assay and oberserved under electron microscopy. Serum alanine aminotransferase （ALT）and liver tissue hydroxyproline （Hyp） content were tested.RESULTS： The liver fibrosis did not automaticallyreverse, which was similar to previous reports, the perilobular deposition of iron accompanied with collagen showed marked characteristics at both the first and 21st d after cessation of DMN injection. However, fat accumulation in hepatocytes occurred only at the 21^st d after cessation of DMN injection.CONCLUSION： Iron deposition and fat accumulation may play important roles in pathological changes in DMN-induced rat liver fibrosis. The detailed mechanisms of these characteristics need further research.

Upregulation of caveolin-1 and SR-B1 in mice with non-alcoholic fatty liver disease

BACKGROUND:Non-alcoholic fatty liver disease(NAFLD)is one of the most frequent causes of liver diseases,with markedly increased prevalence.However,its mechanisms are not clear.The present study was undertaken to illustrate the role of caveolin-1(cav1)and the scavenger receptor class B type 1(SR-B1)in NAFLD.METHODS:Adult male C57BL/6 mice were fed with a normal diet or high fat and cholesterol(HFC)diet for 14 weeks.The mice were sacrificed to collect plasma and harvest the liver;their plasma lipid concentration was measured.Hepatic cav1and SR-B1 mRNA and protein expression were determined by real-time quantitative polymerase chain reaction(qPCR)and Western blotting,respectively.In order to study cav1 and SR-B1distribution and change in hepatocytes,immunohistochemical analysis was performed.RESULTS:HFC diet increased plasma lipids,induced NAFLD and increased the liver/body weight ratio.Compared to the control mice(n=6),the mRNA and protein levels of cav1 and SR-B1 in liver tissue of the NAFLD mice(n=12)increased significantly(cav1 mRNA:1.536±0.226 vs 0.980±0.272,P【0.05;protein:0.643±0.240 vs 0.100±0.130,P【0.01;SR-B1 mRNA:1.377±0.125 vs 0.956±0.151,P【0.01;protein:2.156±0.507vs 0.211±0.211,P【0.01).Furthermore,both cav1 and SR-B1immunoreactivity increased and their distribution was also changed,mainly in the plasma membrane of hepatocytes,cytoplasm and membrane of lipid droplets and around.CONCLUSION:NAFLD is associated with increased concentration of plasma lipids and upregulation of hepatic cav1 and SR-B1 gene and protein expressions,which indicate that cav1 and SR-B1 might play crucial roles in the pathogenesis of NAFLD.

Estimation of visceral fat is useful for the diagnosis of significant fibrosis in patients with non-alcoholic fatty liver disease

BACKGROUND Obesity is a risk factor for non-alcoholic fatty liver disease(NAFLD),although obese patients with NAFLD do not always develop significant fibrosis.The distribution of body fat could predict the risk of NAFLD progression.AIM To investigate the role of bioelectrical impedance-estimated visceral fat(VF)in assessing NAFLD severity.METHODS In this cross-sectional study,patients with biopsy-proven NAFLD were prospectively included.All patients underwent anthropometric evaluation,blood tests and bioelectrical impedance analysis.RESULTS Between 2017 and 2020,119 patients were included[66.4%male,56 years(SD 10.7),62.2%obese,61.3%with metabolic syndrome].Sixty of them(50.4%)showed significant fibrosis(≥F2)in liver biopsy.Age,VF and metabolic syndrome were associated with significant fibrosis(61 years vs 52 years,16.4 vs 13.1,73.3%vs 49.2%,respectively;P<0.001 for all).In the multivariate analysis,VF and age were independently associated with significant fibrosis(VF,OR:1.11,95%CI:1.02-1.22,P=0.02;age,OR:1.08,95%CI:1.03-1.12,P<0.01).A model including these variables showed and area under the receiver operating characteristic curve(AUROC)of 0.75,which was not inferior to transient elastography or NAFLD fibrosis score AUROCs.We developed a nomogram including age and VF for assessing significant fibrosis in routine practice.CONCLUSION VF is a surrogate marker of liver fibrosis in patients with NAFLD.Bioelectrical impedance analysis is an inexpensive and simple method that can be combined with age to guide patient referral when other resources may be unavailable.

Nutritional recommendations for patients with non-alcoholic fatty liver diseases

Fatty liver is the most common liver disease worldwide.Patients with fatty liver disease die primarily from cardiovascular disease and not from chronic liver diseases.Hyperglycemia and hyperinsulinemia induce lipogenesis,thereby increasing the hepatic pool of fatty acids.This pool is also increased by increased delivery of fatty acids through the diet or lipolysis in adipose tissue.Nutritional consultations and lifestyle modification are important in the treatment of non-alcoholic fatty liver disease(NAFLD).Among the dietary constituents,combination of vitamin D,vitamin E,and omega-3 fatty acids shows promise for the treatment of NAFLD.

Dietary supplementation with a high dose of daidzein enhances the antioxidant capacity in swine muscle but experts pro-oxidant function in liver and fat tissues

Background： Although isoflavones are natural dietary antioxidants, they may have toxicological effects. This study aimed to evaluate the redox system in tissues of finishing pigs by supplementation with high dose of daidzein（640 mg/kg）.Results： The supplementation of high dose of daidzein for 64 d increased the activity of superoxide dismutase and total antioxidant capacity in longissimus muscle but down-regulated the expression of reactive oxygen species（ROS）-producing enzyme NADPH oxidase-2 and cyclooxygenase-2. In contrast, high-level supplementation with daidzein exerted pro-oxidant changes in back fat, abdominal fat, liver, and plasma, as reflected by increased contents of malondialdehyde, a lipid peroxidation product, in these tissues. Furthermore, daidzein supplementation resulted in higher expression of ROS-producing enzymes, including NADPH oxidase-1 and cyclooxygenase-1in liver, 5-lipoxygenase（5-LOX） in backfat and NADPH oxidase-2 both in abdominal fat and backfat. The supplementation of daidzein did not affect meat quality parameters in longissimus muscle, including marbling score,eye muscle areas, intramuscular fat, shear force, drip loss, p H and meat color.Conclusions： This experiment suggests that dietary supplementation of finishing pigs with daidzein at a high dose level improves redox status in muscle but exerts pro-oxidant effect in liver and fat tissues.