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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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Non-alcoholic fatty liver disease (NAFLD) is characterized by increased fat depositions in the liver while the patients do not have drinking history.NAFLD has a prevalence of 10％ ～40％ in global,25％ ～26％ in Western populations.From 2004 to 2013,the numbers of new patients on the waitlist who had NASH increased by 170％ in America.The prevalence of NAFLD in China is 20％.With the decrease of HBV and HCV and the increase of diabetes mellitus type 2 and obesity,NAFLD will become the most common chronic liver disease in China over the next 20 years.NAFLD related end-stage liver disease will become the most common indication of liver transplantation.In this paper,the epidemiological features,pathogenesis,indication and prognosis of liver transplantation are reviewed.
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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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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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Clinical data of 113 patients with non-alcoholic fat liver disease (NAFLD) diagnosed by liver biopsy from January 2015 to January 2017 in Taizhou People's Hospital were retrospectively reviewed . Patients all underwent transient elastographic ( TE) examination and the values of fat attenuation index (FAI) were obtained.The hepatocyt fatty changes in pathological examination were scored as 0 (＜5%, n＝40), 1 (5%-33%,n ＝27), 2 (34% -66%,n ＝28) and 3 (＞66%, n ＝18).There were significant differences in AST , Glu, TC and FAI among patients with hepatocyte fatty change scores 0, 1, 2 and 3, and the FAI was significantly correlated with the degree of fatty liver disease .The areas under the ROC curve (AUCs) of FAI in patients with hepatocyte fatty change scores 1, 2 and 3 were 0.78, 0.90 and 0.96, respectively.Logistic regression analysis showed that FAI was correlated with TG , TC and BMI.The results suggest that FAI in TE can be a non-invasive, rapid and objective evaluation method for patients with NAFLD.
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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 study the relationship between microalbuminuria and cardiac diastolic function in patients with type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD). Methods A total of 262 patients with T2DM and NAFLD were included in this study. Patients were divided into normal group (n=106) and abnormal group (n=156) according to their cardiac diastolic function. Data of waist circumference (WC), low density lipoprotein cholesterol (LDL-C), triglyceride(TG), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), fasting insulin level (FINS), insulin resistance index (HOMA-IR), glycosylated hemoglobin (HbA1c), glomerular filtration rate (GFR), C reactive protein (CRP), urinary microalbuminuria excretion rate (UAER), left ventricular myocardial quality index (LVWI) and liver fat content (LFC) were compared between two groups. All patients were divided into four groups according to data of UAER and GFR:group A[UAER<20μg/min and GFR≥90 mL/(min · 1.73 m2)], group B [UAER<20μg/min and GFR<90 mL/(min·1.73 m2)], group C [UAER≥20μg/min and GFR≥90 mL/(min·1.73 m2)], and group D [UAER≥20μg/min and GFR<90 mL/(min · 1.73 m2)]. The differences between the relevant indicators were analyzed between groups. Logistic regression analysis was used to compare UAER between normal group and abnormal group. Also the relationship between the related factors and cardiac diastolic function was compared between these two groups. Results For abnormal group, TG, SBP, HOMA-IR, CRP, UAER, LVWI and LFC were significantly higher, and GFR was significantly lower, than those of normal group (P<0.05). There were no significant differences in other indicators between two groups. Values of peak early/late diastolic filling velocity (E/A) showed a reduction trend in order in A, B,C and D groups (P<0.05). Values of LVWI showed a increasing trend in order in four groups (P<0.05). Values of LFC were significantly higher in C and D groups compared with those of A and B groups (P<0.05). There was no significant difference in LFC between A group and B group. The GFR<90 mL/(min·1.73 m2)was an independent risk factor for cardiac diastolic function in normal group of UAER, and higher UAER was an independent risk factor for cardiac diastolic function in the abnormal group of UAER. Conclusion There is obviously reduced cardiac diastolic function in patients with T2DM and NAFLD and microalbuminuria. When UAER≥20 μg/min, the higher UAER is an independent risk factor for reducing diastolic cardiac dysfunction.
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Objective To analyze the influence of hepatosteatosis on pancreatic β-cell function in type 2 diabetes mellitus (T2DM).Methods A total of 213 subjects with T2DM from Metabolic Disease Hospital,Tianjin Medical University from January 2013 to December 2013 were included in the study.Non-alcoholic fatty liver disease (NAFLD) was diagnosed with abdominal ultrasonography.Patients were divided into two groups:T2DM with NAFLD and T2DM without NAFLD.ALT,AST,γ-glutamyltransferase,serum lipid,glycosylated hemoglobin A1 c (HbA1c),fructosamine,fasting glucose,insulin and 2 hours plasma glucose,insulin after 75g glucoseload were detected.The insulin resistance and β-cell function were assessed by HOMA-IR and HOMA-β.Results Among the 213 T2DM subjects,51％ (108 cases) were with NAFLD.The HOMA-IR [4.76 (2.83,7.21) vs 2.79 (1.76,4.37),P ＜ 0.05] and HOMA-β [49.18 (37.78,85.09) vs 29.50 (18.09,45.54),P ＜ 0.05] were significantly higher in T2DM with NAFLD than those in T2DM alone.Within subjects with T2DM and NAFLD,the HOMA-IR [6.28 (2.87,8.17) vs 2.95 (2.07,3.66) P ＜ 0.05] and HOMA-β [59.18 (37.78,85.09) vs 30.59 (28.56,34.49),P ＜ 0.05] levels were higher in subjects with normal liver function than those with abnormal liver function.Conclusions T2DM patients with NAFLD have severer insulin resistance than those without NAFLD.The β-cell function of those patients was compensatory increased,which was decreased in subjects with abnormal liver function.
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Objective To investigate the association between the Adiponectin rs266729 and rs2241766 gene polymorphisms and nonalcoholic fatty liver disease in the Han Chinese population residing in Qingdao. Methods Adiponectin rs266729 and rs2241766 gene polymorphisms were genotyped in patients with NAFLD (n = 336) and healthy controls (n = 280) using polymerase chain reaction (PCR). Serum lipid profiles and adiponectin levels were determined using biochemical methods. Statistical analyses were performed using Pearson Chi square test, logistic regression analysis, t test, linear regression analysis. Results We found a significant association between the Adiponectin rs266729 genotype frequencies and allele frequencies between NAFLD pa-tients and controls (χ2= 9.929, P = 0.007; χ2= 9.809, P = 0.002). After adjustment of confounding factor, the rs266729 G allele was associated with an increased risk of NAFLD compared to the C allele (OR = 1.410, 95%CI: 1.082-1.831, P = 0.008) No significant differences were found in the rs2241766 genotype frequencies and allele frequencies between NAFLD population and the controls (OR = 1.410, 95%CI: 1.082-1.831, P = 0.008). Conclusion The Han Chinese in Qingdao carrying the rs266729 G allele are at increased risk of NAFLD.
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Objective To investigate the changes and clinical significance of serum total and high molecular weight adiponectin (HMW APN) levels in type 2 diabetic patients with non-alcoholic fatty liver disease (NAFLD).Methods Serum levels of total adiponectin and HMW APN were measured by ELISA,in 58 type 2 diabetic patients with nonalcoholic fatty liver disease (T2DM with NAFLD group),59 type 2 diabetic patients without nonalcoholic fatty liver disease (T2DM group),and 55 control subjects with normal glucose tolerance and without nonalcoholic fatty liver disease (NC group).Results (1) Alanine transaminase and total cholesterol levels were significantly higher in T2DM with NAFLD group than those in NC group(P＜0.01),while body mass index (BMI),aspartate aminotransferase,triglyceride (TG),and fasting insulin were also significantly increased (P＜0.05 or P＜ 0.01),and high density lipoprotein-cholesterol (HDL-C) were significantly decreased compared with those in NC and T2DM groups (P＜0.01).(2) Total adiponectin,HMW APN,and the ratio of HMW APN to total adiponectin in T2DM group were lower than those in NC group.Total adiponectin and HMW APN levels in T2DM with NAFLD group were significantly lower than those in T2DM group(P＜0.01).(3) Regression analysis showed that homeostasis model assessment insulin resistance index (HOMA-IR),TG,and HDL-C levels were independent predicting factors for total adiponectin and HMW APN levels.TG and BMI were independent risk factors for T2DM complicated with NAFLD,while total adiponectin and HMW APN levels were the protective ones (OR =0.701,0.489,respectively).Conclusions Hypoadiponectinemia may partially play an important role in the development and progression of NAFLD in T2DM.
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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
Objective To explore cardiovascular risk factors in patients of hypertension (HTN) complicated with non-alcoholic fatty liver but normal aminotransferase. Methods Forty-four cases (control group) of uncomplicated hypertension and 56 cases (study group) of hypertension complicated with nonalcoholic fatty liver but normal aminotransferase were screened from those who visited physical examination center of the hospital for regular checks-up during October 2009 to June 2010. Blood pressure ( BP), body mass index ( BMI), fasting plasma glucose (FPG), total serum cholesterol (TC) , triglyceride (TG), highdensity lipoprotein-cholesterol ( HDL-C ), low-density lipoprotein-cholesterol ( LDL-C ), gammaglutamyltransferase ( GGT ), uric acid ( UA ) , highly-sensitive C-reactive protein ( hs-CRP) and homocysteine (Hey) of the two groups were compared. Results Comparing with the control group, the study group had higher diastolic blood pressure ( DBP) (t = 1898. 5, P < 0. 05) , BMI (t = - 5. 036, P < 0.01), FPG (t= -2.026, P<0.05), TG (t = 1923. 5, P<0.05), GGT (t = 1789, P <0.01), UA 0 = 1715, P<0.01), hs-CRP (t = 1832.5, P < 0.01) and lower level of HDL-C (t =2357.0, P< 0. 01). Serum activity of GGT correlated positively with BMI (rs = 0. 349, P = 0. 000), TG ( rs = 0.413,P =0.000), UA (rs =0.446, P= 0.000) and hs-CRP (rs =0.350, P = 0.000), respectively.Conclusions When patients of hypertension complicated with non-alcoholic fatty liver but normal aminotransferase, their cardiovascular risk factors clustered further, with serum activity of GGT obviously increased which correlated positively with various risk factors, indicating increase in cardiovascular risks.
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Objective To study the effect of serum leptin in “two hits” of nonalcoholic fatty liver disease (NAFLD).Methods Fasting serum leptin(LEP) ,malondialdehyde(MDA) ,hyaluronic- acid(HA) ,type Ⅲ procollagen ( PCⅢ), laminin ( LN), and type Ⅳ collagen ( Ⅳ-C ) were detected in 43 simple nonalcoholic fatty liver( NAFL ) patients ,41 NASH patients and 40 healthy subjects. Insulin resistance was estimated by HOMA value and its relatio nship with leptin level in NAFLD was analyzed. The severity of lipid peroxidation was estimated by MDA and its relationship with leptin level in NAFLD was analyzed. The relationship of serum fibrosis markers with leptin level in NAFLD also was analyzed. Results Serum leptin, HOMA value in NAFLD were higher than those of healthy controis. MDA,PC Ⅲ 、Ⅳ-C 、LN 、HA in NASH were higher than those of healthy controls or simple NAFL patients. ,HOMA value, in NAFLD positively correlated with leptin. MDA, PC Ⅲ、 Ⅳ-C 、LN、HA in NASH positively correlated with leptin. Conclusion Serum leptin closely correlated with insulin resistance which results in “First hit” of NAFLD. There was certain relationship of leptin with “Second hit” of NAFLD. Leptin should be one of the factors which result in liver fibrosis.