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Objective:To analyze the status quo and influencing factors of non-alcoholic fatty liver disease in community-dwelling elderly women.Methods:A total of 9 754 female residents aged 60-79 years who attended health check-up in Anting Town Community Health Service Center from June 2019 to December 2021 were enrolled in the study. According to the ultrasound diagnosis, there were 5 220 cases of non-alcoholic fatty liver disease (NAFLD group) and 4 534 cases without NAFLD (non-NAFLD group). The general information, physiological and biochemical indicators were compared between two groups with Mann-Whitney U test and Chi-square test; the influence factors of NAFLD were analyzed with logistic regression. Results:The overall prevalence of NAFLD was 53.52%(5 220/9 754), prevalence in the 65-69 age group was the highest and that in the 75-79 age group was the lowest. Body mass index ( Z=47.667), waist circumference ( Z=45.949), waist-to-hip ratio ( Z=30.805), systolic blood pressure ( Z=7.543), diastolic blood pressure ( Z=7.621), fasting blood glucose ( Z=20.298), glycated hemoglobin ( Z=23.588), alanine aminotransferase ( Z=29.624), aspartate aminotransferase ( Z=7.824), total bilirubin ( Z=4.441), triglyceride ( Z=34.597), low-density lipoprotein cholesterol ( Z=2.476) and blood uric acid ( Z=29.934) levels of NAFLD group were significantly higher than those in non-NAFLD group (all P<0.05); the mean age ( Z=-3.885) and high density lipoprotein cholesterol ( Z=-23.553) in NAFLD group were significantly lower than those in non-NAFLD group (all P<0.001); there were no significant differences in the levels of total cholesterol ( Z=1.762)and creatinine ( Z=1.453) between the two groups (all P>0.05). The proportion of patients had type 2 diabetes mellitus ( χ2=368.395), hypertension ( χ2=208.503), hypertriglyceridemia ( χ2=883.831), hyperuricemia ( χ2=228.562), central obesity ( χ2=1 506.580), high risk of stroke ( χ2=605.322) and high risk of ASCVD ( χ 2=309.434) in NAFLD group were significantly higher than that of non-NAFLD group (all P<0.001). Logistic regression analysis showed that age ( OR=0.937, 95% CI: 0.928-0.946), body mass index ( OR=1.224, 95% CI:1.194-1.255), waist circumference ( OR=1.072, 95% CI: 1.062-1.082), glycosylated hemoglobin ( OR=1.348, 95% CI: 1.275-1.426), alanine aminotransferase ( OR=1.032, 95% CI: 1.026-1.037), triglyceride ( OR=1.757, 95% CI: 1.646-1.875) and serum uric acid ( OR=1.004, 95% CI: 1.004-1.005) levels were the influencing factors for NAFLD in elderly women (all P<0.001). Conclusion:The prevalence rate of non-alcoholic fatty liver disease in the community-dwelling elderly women is high, which are associated with multiple influencing factors.
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Objective:To study the therapeutic effect of liraglutide on rat models with non-alcoholic fatty liver disease (NAFLD) and its influence on the expression of fibroblast growth factor 21 (FGF21).Methods:Thirty five Sprague Dawley (SD) rats were randomly divided into normal control group (15 rats) and control group (20 rats). They were fed with normal diet and high fat diet respectively. The NAFLD rat model was established by feeding the model group for 12 weeks. After successful modeling, the model group was randomly divided into liraglutide group and model group. 600 μg/(kg·d) liraglutide and equal volume normal saline were injected intraperitoneally respectively. All rats were killed at the 16th week. Serum FGF21, alanine aminotransferase (ALT), aspartate aminotransferase (AST), fasting blood glucose (FBG), triglyceride (TG) and total cholesterol (TC) were measured; Hematoxylin-eosin (HE) staining was used to observe the pathological changes of rat liver tissue, and real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of FGF21 mRNA in rat liver tissue.Results:The liver index and serum ALT, AST, TC and TG contents in model group were significantly higher than those in normal control group (all P<0.05). The above indexes in liraglutide group were significantly lower than those in model group (all P<0.05). There was no significant difference in serum FBG level among the three groups ( P>0.05). HE staining showed that there were no abnormal pathological changes in liver of normal control group. Steatosis and inflammatory cell infiltration occurred in liver cells of model group. Compared with model group, liver steatosis and inflammatory cell infiltration in liraglutide group were significantly reduced. The level of FGF21 in serum and mRNA expression of FGF21 in liver tissue in model group were significantly higher than those in normal control group ( P<0.05). The levels of FGF21 in serum and FGF21 mRNA in liver tissue in liraglutide group were lower than those in model group ( P<0.05). Conclusions:Liraglutide can effectively delay the development of NAFLD in rats, and its mechanism may be related to the regulation of the expression of FGF21.
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Extracellular vesicles (EVs) are small bilayer lipid membrane vesicles that can be released by most cell types and detected in most body fluids. EVs exert key functions for intercellular communication via transferring their bioactive cargos to recipient cells or activating signaling pathways in target cells, and hence participate in the variety of diseases including the occurrence and development of liver diseases. In recent years, the prevalence of nonalcoholic fatty liver disease (NAFLD) has increased. Currently there is no reliable method except invasive liver biopsy for the diagnosis of liver inflammation or fibrosis staging. Therefore, the search for the corresponding markers of noninvasive circulation continues to be active, and extracellular vesicles are one of the most concerned. To this end, we reviewed current knowledge about the physical characteristics, biological components, and isolation methods of extracellular vesicles, and introduced the concept of using circulating cell-derived vesicles as a new diagnostic marker for nonalcoholic fatty liver disease.
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Hepatocellular carcinoma (HCC) is a major disease with a high degree of malignancy, and poor prognosis, which seriously endangers human health. Chronic viral hepatitis (HBV, HCV)-cirrhosis-liver cancer patterns of pathogenesis has been widely accepted. However, the relationship between non-infectious liver disease and HCC is not completely clear; thereby how various non-infectious liver diseases develop through precancerous lesions has attracted widespread attention to HCC. A full understanding of these precancerous lesions is likely to provide new ideas and strategies for the prevention and treatment of non-infectious liver disease-related HCC.
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Objective@#To investigate the relationship between gut microbiota structure and biochemical changes in patients with different types of nonalcoholic fatty liver disease (NAFLD), in order to provide evidence for clinical diagnosis and prevention of NAFLD.@*Methods@#Forty-eight NAFLD cases (NAFLD group), 40 NAFLD cases with type 2 diabetes mellitus (NAFLD combined with type 2 diabetes mellitus group) and 30 healthy cases (healthy group) were randomly enrolled, and their body mass index, serum alanine aminotransferase, aspartate aminotransferase, total bilirubin, total cholesterol, triglyceride, high density lipoprotein, low density lipoprotein and uric acid were measured. Serum levels of TNF-alpha and fasting insulin were measured using ELISA, and then insulin resistance index was calculated. The gut microbiota of three groups of subjects was detected using 16S rDNA-based high-throughput sequencing. Lastly, the correlations between the various factors were analyzed. The comparison among groups was conducted by 2 test, and one-way ANOVA was used for comparison among groups with normal distribution and homogeneity of variance. Furthermore, the LSD method was used to compare the two groups. K-W rank sum test was used for comparison among groups without normal distribution or homogeneity of variance.@*Results@#Body mass index, aspartate aminotransferase, triglyceride, total cholesterol, low density lipoprotein, uric acid, tumor necrosis factor-alpha, fasting insulin and insulin resistance index of NAFLD group were higher than healthy group, while the high-density lipoprotein was lower in the healthy group, and the difference was statistically significant (P< 0.05). Compared with NAFLD group, the life expectancy, fasting blood glucose and insulin resistance index of NAFLD combined with type 2 diabetes mellitus group were higher, while the body mass index, aspartic acid aminotransferase, total cholesterol and HDL levels were decreased, and the difference was statistically significant (P< 0.05). NAFLD group (P= 0.016) had decreased abundance of firmicutes than healthy group, and the abundancy of the firmicutes in the NAFLD combined with type 2 diabetes group was significantly lower (P< 0.001). The abundance of bacteroidetes in NAFLD combined with type 2 diabetes group was higher than healthy group, and the difference was statistically significant (P= 0.006). At the "genus level," the abundance of Roseburia and Subdoligranulum in the NAFLD group was decreased, while the Roseburia in the NAFLD group with type 2 diabetes group was significantly lower (P< 0.05). In addition, the abundance of Faecalibacterium, Blautia, Anaerostipes and Fusicatenibacter in NAFLD combined with type 2 diabetes group was lower than healthy group, and the difference was statistically significant (P< 0.001). Fusicatenibacter, Blautia, Anaerostipes, Faecalibacterium, and Roseburia were negatively correlated with fasting blood glucose and insulin resistance index levels (r< 0,P< 0.05), and positively correlated with high-density lipoprotein levels (r> 0,P< 0.05). Fusicatenibacter was negatively correlated with tumor necrosis factor-alpha (r= -0.211,P= 0.044), and Lachnoclostridium was positively correlated with body mass index, alanine aminotransferase, aspartate aminotransferase levels (r> 0,P< 0.05). Fusobacterium was positively correlated with aspartate aminotransferase level (r= 0.245,P= 0.019). Escherichia-shigella was positively correlated with fasting blood glucose, low-density lipoprotein, alanine aminotransferase, aspartate aminotransferase levels (r > 0,P< 0.05). Megamonas was negatively correlated with high-density lipoprotein levels (r= -0.231,P= 0.027).@*Conclusion@#A structural change of gut microbiota had occurred in patients with NAFLD, suggesting changes in some of these bacterial genuses had relation to insulin resistance and inflammatory response, which may become a new target for the treatment of NAFLD.
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Objective@#To investigate the prevalence and risk factors of non-alcoholic fatty liver disease(NAFLD) in patients with chronic hepatitis B(CHB) receiving antiviral treatment.@*Methods@#The cross-sectional study included 3 477 cases with CHB who received antiviral therapy. The prevalence of NAFLD was investigated, and then the risk factors were screened and analyzed by stepwise regression method in CHB patients with NAFLD as the dependent variable and the related influencing factors as independent variables.@*Results@#The prevalence of NAFLD was 24.1% in CHB patients who received antiviral therapy. After adjusting for age and gender, central obesity (OR: 7.44, 95%CI: 6.06 ~ 9.14), hypertension (OR: 1.74, 95%CI: 1.51 ~ 2.20), and triglyceride (OR: 1.52, 95%CI: 1.18 ~ 1.96) were positively associated with NAFLD, and cirrhosis was negatively associated with NAFLD (OR: 0.42, 95%CI: 0.34 ~ 0.53). Patients with long-term antiviral therapy had increased risk of NAFLD.@*Conclusion@#A significant proportion of CHB patients receiving antiviral therapy have suffered from NAFLD. Therefore, CHB patients receiving long-term antiviral treatment should pay more attention to the prevalence of NAFLD.
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Worldwide increasing prevalence of obesity and lifestyle changes has put nonalcoholic fatty liver disease (NAFLD) as the most prevalent liver disease of the coming decade. NAFLD not only causes cirrhosis and hepatocellular carcinoma, but also acts as a component of metabolic syndrome together with obesity, type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), and dyslipidemia. Consequently, its mutual cause-and-effect interactions have brought a huge clinical and financial burden to patients and society.
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Objective: To evaluate the feasibility of three-dimensional speckle tracking echocardiography (3D-STE) in evaluating left ventricular (LV) function in type 2 diabetes mellitus (T2DM) patients with non-alcoholic fatty liver disease (NAFLD). Methods: Totally 30 T2DM patients without NAFLD (group A), 32 T2DM patients with mild NAFLD (group B) and 35 T2DM patients with moderate to severe NAFLD (group C) underwent 3D-STE. Echocardiographic parameters were obtained, including conventional parameters of the ratio of transmitral peak early to late diastolic velocity (E/A), interventricular septum thickness diastolic (IVSTd), posterior wall thickness diastolic (PWTd), LV end-diastolic diameter (LVDd) and LV end-systolic diameter (LVDs), as well as LV function parameters including end-systolic left atrial volume (LAV), LV mass (LVM), LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), LV mass index (LVMI) and LV ejection fraction (LVEF), also 3D-STE parameters including global longitudinal strain (GLS), global area strain (GAS), global radial strain (GRS) and global circumferential strain (GCS). The correlation of 3D-STE parameters and glycosylated hemoglobin (HbA1c), body mass index (BMI) were analyzed with Pearson linear correlation analysis. Results: There was no difference of E/A, IVSTd, PWTd, LVDd, LVDs, LVMI, LVEF, LVEDV nor LVESV among the 3 groups (all P>0.05), but patients in groups B and A had higher GCS, GRS, GLS and GAS than in group C (all P0.05). Conclusion: 3D-STE can be used to assess LV function in T2DM patients with NAFLD.
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Stearoyl-CoA desaturase-1 (SCD-1) is the key rate-limiting enzyme to catalyze the conversion of saturated fatty acids to monounsaturated fatty acids. The monounsaturated fatty acids in the catalytic products are important substrates for the formation of triglycerides, cholesteryl esters and phospholipids. Therefore, SCD-1 plays an important regulatory role in the metabolic process of fat. Currently, obesity and non-alcoholic fatty liver disease are widely prevalent worldwide. SCD-1 has gradually become a potential drug target for the treatment of such diseases due to its important regulatory role in fat metabolism. We summarize the recent research progress of SCD-1 in obesity and non-alcoholic fatty liver disease and the developmental status of SCD-1 inhibitors in order to provide new ideas and references related to disease and target drugs.
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Objective@#To establish overfed zebrafish model for non-alcoholic steatohepatitis.@*Methods@#The wild-type zebrafish was fed 3 times a day with normal diet. Body length, weight, and triglyceride levels were measured after 20 days of feeding. The changes in expression of genes associated with cholesterol metabolism, lipid metabolism, endoplasmic reticulum stress, and inflammation were detected by quantitative PCR. Liver tissue sections were stained with H&E. Statistical analyses between groups were compared using t-test.@*Results@#The body length (0.71±0.014) cm and body weight (44.83±1.833) mg of model group were higher than that of control group (0.50±0.009) cm and body weight (19.33±2.753) mg (total body length = 12.36, total body weight = 7.71, P < 0.01). Triglyceride content in the model group was (59.15 ± 0.5612) μmol / L, higher than the control group (16.71 ± 0.3562) μmol / L (t = 63.84, P < 0.001). Quantitative PCR results showed that the expression of genes related to cholesterol synthesis in the model group was higher than that in the control group (P < 0.01). The expression levels of lipid production and lipid oxidation related factors in the model group were higher than the control group. The difference between the two groups was statistically significant (P < 0.05). The expression of inflammation-related factors in the model group was higher than that in the control group (P < 0.001), and the expression of genes related to endoplasmic reticulum stress in the model group was higher than that to control group (P<0.001). Liver H&E staining showed that the model group had pathological changes such as large bulla and vesicles compared to the control group.@*Conclusion@#A continuous 3 times 20 days of normal diet can simulate the disease characteristics of human non-alcoholic steatohepatitis in a zebrafish.
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Objectives To investigate the correlation between the triglyceride and glucose (TyG) index and nonalcoholic fatty liver disease (NAFLD) and to evaluate the predictive value of TyG for NAFLD.Methods This retrospective study included 279 individuals aged 60 or over (115 with NAFLD and 164 without NAFLD).Clinical data including height and weight (for body mass index,BMI),presence of diabetes mellitus,lipid-regulating medications,glucose-lowering medications,alanine aminotransferase (ALT),aspartate transaminase (AST),gamma-glutamyltransferase (GGT),albumin,fasting plasma glucose (FPG),serum lipid profiles,serum uric acid,glycosylated hemoglobin,and serum creatinine were collected and analyzed.The TyG index was calculated according to FPG and fasting serum trig[ycerides.Binary logistic regression was carried out to determine the correlation between TyG and NAFLD.Receiver operating characteristic (ROC) curve analysis was used to test the predictive value of TyG and TyG combined with ALT and BMI for NAFLD.Results According to the quartiles of TyG,the subjects were divided into four groups:Q1 (TyG≤ 7.40)、Q2 (TyG≤ 7.80)、Q3(TyG≤＜≤8.31)、Q4(TyG≤8.13).The rates of NAFLD were 16.2％ in Q1,29.6％ in Q2,53.7％ in Q3,and 65.3％ in Q4 (P ＜0.0001).Logistic regression showed that TyG was independently associated with NAFLD;Compared with Group Q1,the adjusted odds ratios (ORs) and 95％ confidence intervals (CIs) for NAFLD of Q2,Q3,and Q4 were 1.677 (95％ CI:0.641-4.384),3.279 (95％ CI:1.285-8.364),and 5.447 (95％ CI:2.172-13.658),respectively.The ROC analysis indicated that the area under the ROC curve (AUC) was 0.730 (95％ CI:0.67-0.79) and that,with the cut-off point at 7.78,the largest Youden's index value was 0.402,with a sensitivity of 74.6％ and a specificity of 65.6％ for NAFLD.When combining TyG with BMI and ALT,the AUC could reach 0.822 (95％ CI:0.771-0.872).Conclusions TyG is correlated with NAFLD in the elderly.Besides,TyG combined with BMI and ALT is effective to predict NAFLD in the elderly.
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Nonalcoholic fatty liver disease (NAFLD) includes nonalcoholic simple fatty liver, nonalcoholic steatohepatitis, liver cirrhosis, and liver cancer and is the most common liver disease in the world. The complex pathogenesis of NAFLD is a major concern among researchers. CD36 is a transmembrane glycoprotein that takes up fatty acid and binds to oxidized low-density lipoprotein in the liver, and therefore, it is involved in the development and progression of NAFLD. With reference to the latest research findings, this article reviews the association between CD36 and NAFLD and the role of CD36.
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Non-alcoholic fatty liver disease is a common chronic liver disease closely associated with obesity, hyperlipidemia, and diabetes. It can gradually progress to liver cirrhosis or even hepatocellular carcinoma; however, there are still no specific therapeutic agents for this disease. Liraglutide is a human glucagon-like peptide-1 analogue and has a marked effect in the treatment of type 2 diabetes. At present, many studies indicate that liraglutide also has a certain therapeutic effect on non-alcoholic fatty liver disease during the treatment of type 2 diabetes, but its mechanism of action remains unknown. This article reviews the known mechanisms of action of liraglutide in the treatment of non-alcoholic fatty liver disease.
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Nonalcoholic fatty liver disease (NAFLD) has become the most important liver disease in the world and its prevalence rate still tends to increase. However, there are still no effective drugs so far. The complex and dynamic interactions between multiple effects/mediators in the pathophysiology of NAFLD provide new insights and help with stratification and redefinition of clinical phenotypes and evaluation of disease susceptibility and multiplicity of progression. They may also provide new targets for future treatment. Therefore, research on the pathophysiology of NAFLD is imperative. Alcoholic liver disease is a great harm to health and an important cause of end-stage liver disease. Some progress has been made in the research on alcoholic liver disease around the world in 2016. This article reviews the research advances in alcoholic liver disease in 2016 from the aspects of epidemiology, pathogenesis, diagnostic and therapeutic methods, and prognosis.
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Objective@#To investigate the effect of calcium-independent phospholipase A2 (iPLA2) inhibitor in reducing hepatocyte lipoapoptosis and improving insulin resistance.@*Methods@#A total of 28 male Sprague-Dawley rats were randomly divided into the following three groups: 12 rats in group I (normal control group) were given normal diet for 18 weeks; 8 rats in group II (non-alcoholic fatty liver disease model group) were given high-fat diet for 18 weeks; 8 rats in group III (iPLA2 inhibitor group) were given high-fat diet for 18 weeks and intraperitoneal injection of the iPLA2 inhibitor bromoenol lactone 150 μg/kg once every other day since week 15 (14 times of injection in total). All the rats were sacrificed at the same time, and body weight and liver weight were measured. Blood lipids, serum enzymes, fasting blood glucose, fasting insulin, free fatty acid, and serum iPLA2 concentration were measured in each group, and liver pathological changes were evaluated. The terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling was used to measure the level of hepatocyte apoptosis and the apoptotic index was calculated. Quantitative PCR was used to measure the mRNA expression of iPLA2. The Student-Newman-Keuls test and the chi-square test were used for comparison of parameters between groups I, II, and III. P < 0.05 was considered statistically significant.@*Results@#Compared with group I, group II had significant increases in triglyceride (0.75±0.05 mmol/L vs 1.20±0.13 mmol/L, P < 0.05), cholesterol (1.50±0.12 mmol/L vs 2.94±0.34 mmol/L, P < 0.05), low-density lipoprotein (0.65±0.06 mmol/L vs 1.30±0.16 mmol/L, P < 0.05), free fatty acid (0.58±0.09 mEq/L vs 0.80±0.20 mEq/L, P < 0.05), fasting blood glucose (4.85±0.22 mmol/L vs 6.94±0.65 mmol/L, P < 0.05), and fasting insulin (0.89±0.52 mmol/L vs 1.29±0.52 mmol/L, P < 0.05), and a significant reduction in the insulin sensitivity index (0.52±0.21 vs 0.27±0.11, P < 0.05); group II also had significant inflammation and fatty degeneration shown by liver pathology, and compared with group I, group II had significant increases in apoptotic cells and apoptotic index (0.58%±0.17% vs 39.69%±4.96%, P < 0.05). Compared with group I, group II had significant increases in serum iPLA2 concentration (2.92±0.08 ng/ml vs 3.28±0.14 ng/ml, P < 0.05) and the mRNA expression of iPLA2 in the liver (1.07±0.18 vs 7.68±0.49, P < 0.05). Compared with group II, group III had a lower level of hepatocyte apoptosis, a significant reduction in apoptotic index (39.69%±4.96% vs 24.80%±2.53%, P < 0.05), significant reductions in serum iPLA2 concentration (3.28±0.14 ng/ml vs 2.64±0.24 ng/ml, P < 0.05) and the mRNA expression of iPLA2 in the liver (7.68±0.49 vs 2.60±0.36, P < 0.05), significant reductions in fasting insulin (1.29±0.52 mmol/L vs 0.80±0.09 mmol/L, P < 0.05) and fasting blood glucose (6.94±0.65 mmol/L vs 5.18±0.35 mmol/L, P < 0.05), and a significant increase in insulin sensitivity index (0.27±0.11 vs 0.45±0.09, P < 0.05).@*Conclusion@#There is a significant increase in the expression of iPLA2 in rats with non-alcoholic fatty liver disease, and iPLA2 inhibitor can reduce hepatocyte lipoapoptosis and improve insulin resistance.
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Objective To investigate the effects of Panax japonicas hypolipidemic compound (ZDS) on the lipid metabolism and its possible mechanism in non-alcoholic fatty liver disease (NAFLD) mice induced by high sugar and fat diet.Methods The extracts of Panaax japonica rhizoma,Salviae Miltiorrhiz radix Et rhizoma and Crataegi Fructus were prepared,and ZDS compound was formulated according to their antioxidant activities.Forty SPF male Kunming mice were randomly divided into four groups (10 each):normal control group,model group,high-dose ZDS-treated group,and low-dose ZDS-treated group.In addition to the mice in normal control group were given conventional diet,the mice in other three groups were fed high-sugar high-fat diet.High-dose and low-dose ZDS-treated group were given 90mg/kg or 30mg/kg ZDS.After the treatment of five weeks,the histomorphology and lipid deposition of the liver were observed to confirm the establishment of mouse NAFLD model and the improvement of ZDS compound on lipid deposition.The relative expression of miR-34a,SIRT1,and lipid metabolism related genes (FASN,ACC1) was detected by RT-qPCR and RT-PCR.SIRT1 protein expression was detected by Western blotting.Results Compared with the normal group,the morphological results showed hepatic lipid accumulation in the model group was more serious,the levels of triglyceride (TG) and miR-34a in the liver tissue increased significantly (P＜0.05),the expression levels of SIRT1 decreased,and the gene of lipid metabolism such as FASN,ACC1 significantly increased (P＜0.05).However,compared with the model group,ZDS compound improve hepatic lipid accumulation,liver TG content significantly decreased (P＜0.05),liver tissue miR-34a,FASN and ACC1 expressions decreased,while SIRT1 expression increased (P＜0.05).The protein expression of SIRT1 was consistent with its mRNA expression.Conclusion ZDS compound can effectively improve liver cell steatosis through the miR-34a/SIRT 1 pathway involved in lipid metabolism regulation,thus providing a new idea for early intervention of NAFLD through traditional Chinese compound medicine.
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CONTEXT: Non-alcoholic fatty liver disease (NAFLD), hepatic manifestation of metabolic syndrome, has been considered the most common liver disease nowadays, which is also the most frequent cause of elevated transaminases and cryptogenic cirrhosis. The greatest input of fatty acids into the liver and consequent increased beta-oxidation contribute to the formation of free radicals, release of inflammatory cytokines and varying degrees of hepatocytic aggression, whose histological expression may vary from steatosis (HS) to non-alcoholic steatohepatitis (NASH). The differentiation of these forms is required by the potential risk of progression to cirrhosis and development of hepatocellular carcinoma. OBJECTIVE: To review the literature about the major risk factors for NAFLD in the context of metabolic syndrome, focusing on underlying mechanisms and prevention. METHOD: PubMed, MEDLINE and SciELO data basis analysis was performed to identify studies describing the link between risk factors for metabolic syndrome and NAFLD. A combination of descriptors was used, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, metabolic syndrome and risk factors. At the end, 96 clinical and experimental studies, cohorts, meta-analysis and systematic reviews of great impact and scientific relevance to the topic, were selected. RESULTS: The final analysis of all these data, pointed out the central obesity, type 2 diabetes, dyslipidemia and hypertension as the best risk factors related to NAFLD. However, other factors were highlighted, such as gender differences, ethnicity, genetic factors and the role of innate immunity system. How these additional factors may be involved in the installation, progression and disease prognosis is discussed. CONCLUSION: Risk factors for NAFLD in the context of metabolic syndrome expands the prospects to 1) recognize patients with metabolic syndrome at high risk for NAFLD, 2) elucidate pathways common to other co-morbidities, 3) determine risk factors associated with a worse prognosis, 4) develop therapeutic strategies with goal of reducing risk factors, 5) apply acquired knowledge in public health policies focusing on preventive strategies.
CONTEXTO: A doença hepática gordurosa não alcoólica (DHGNA) vem sendo considerada a manifestação hepática da síndrome metabólica e a hepatopatia mais frequente da atualidade, sendo também a causa mais frequente de aumento das transaminases e de cirrose criptogênica. O maior aporte de ácidos graxos ao fígado e consequente aumento da beta-oxidação concorrem para formação de radicais livres, liberação de citocinas inflamatórias e graus variáveis de agressão hepatocítica, cuja expressão histológica pode variar da esteatose hepática (EH) à esteatohepatite não-alcoólica (EHNA), cuja diferenciação se faz necessária pelo risco potencial de progressão para cirrose e desenvolvimento do carcinoma hepatocelular. OBJETIVO: Revisar a literatura sobre os principais fatores de risco para a DHGNA no contexto da síndrome metabólica, com foco nos mecanismos subjacentes e nas estratégias de prevenção. MÉTODO: Foi realizada pesquisa bibliográfica no PubMed para identificar estudos que descrevessem a associação entre os fatores de risco para síndrome metabólica e a DHGNA, utilizando-se a combinação de descritores: "Non-alcoholic fatty liver disease, Non-alcoholic steatohepatitis, metabolic syndrome and risk factors". Foram selecionados 96 estudos clínicos, experimentais, de cohort, metanálises e revisões sistemáticas de maior impacto e relevância científica para o tema. RESULTADOS: A análise das informações consolidou a obesidade central, diabetes melitus tipo 2, dislipidemia e hipertensão como os fatores de risco mais bem relacionados à DHGNA. Entretanto, outros fatores foram destacados, como diferenças entre gêneros, etnia, fatores genéticos e o papel da imunidade inata, como estes fatores adicionais que podem estar implicados na instalação, progressão e prognóstico da doença. CONCLUSÃO: O conhecimento dos fatores de risco para a DHGNA no contexto da síndrome metabólica amplia os caminhos para: 1) reconhecer pacientes com risco elevado para a doença; 2) elucidar vias comuns a outras comorbidades; 3) determinar fatores de risco relacionados a pior prognóstico; 4) desenvolver estratégias terapêuticas com o objetivo de reduzir fatores de risco; 4) aplicar os conhecimentos adquiridos nas políticas públicas de saúde com foco em estratégias preventivas.
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Humans , Fatty Liver/etiology , Metabolic Syndrome/complications , Disease Progression , Risk FactorsABSTRACT
No abstract available.
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No abstract available.
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AIM: To investigate the effect of mfn2 on mitochondrial function in steatosis hepatocytes. METHODS: Plasmid pEGFP-mfn2 was transfected into hepatocyte strain L02 by Lipofectamine 2000 in vitro, then the steatosis model of hepatocytes was establish by oleic acid induction. RT-PCR was used to evaluate mRNA expression and Western blotting was use to detect the protein expression. ATP level was determined by firefly luciferase bioluminescent. ROS production was measured by fluorescence probe DCFH-DA. Chondrosome transmembrane potential of L02 was observed by labeling of JC-1 and FCM. RESULTS: The stable expression of ectogenesis mitofusin2 in L02 cells was confirmed by RT-PCR and Western blotting. In the model of oleic acids induced lipid formation, Mfn2 obviously inhibited the descent of chondrosome transmembrane potential and ATP level, and increased ROS production in L02 cells. CONCLUSION: Up-regulated expression of mfn2 attenuates mitochondria dysfunction caused by oleic acids induced lipid formation.