The Relationship between Nonalcoholic Fatty Liver Disease and Retinopathy in NHANES III

BackgroundNonalcoholic fatty liver disease (NAFLD), an emerging multisystem disease, has the similar pathogenesis with diabetes and is prevalent in diabetes. This study investigated whether NAFLD is associated with retinopathy in individuals with diabetes and without diabetes.MethodsThe association between NAFLD and retinopathy was investigated in 5963 participants aged 40 years and older who participated in the NHANES III, a nationally representative, population-based and cross-sectional study. NAFLD was detected via ultrasonography, and fundus photographs were obtained to grade retinopathy patterns. We performed multivariate logistic regression analysis to investigate the relationship between the presence of retinopathy and NAFLD and diabetes.ResultsAfter adjusting for multiple covariates, NAFLD population had no evidence of retinopathy increase in population without diabetes (odds ratio [OR]: 0.77; 95% confidence interval [CI]: 0.48 to 1.26). In addition, NAFLD in individuals with diabetes was not significantly associated with retinopathy (OR: 0.77; 95% CI: 0.47 to 1.26), independent of age, gender, ethnicity, waist circumference, serum high-density lipoprotein (HDL) cholesterol, serum triglycerides, systolic blood pressure, and glycated hemoglobin.ConclusionsIn the US general population, NAFLD is not a precipitating factor of retinopathy in population with or without diabetes.     

代谢正常肥胖个体发生非酒精性脂肪性肝病的相关性研究

目的:探讨代谢正常肥胖(Metabolically healthy obese,MHO)个体与非酒精性脂肪性肝病(Nonalcoholic fatty liver disease,NAFLD)发生的相关性。方法:选择2006年4月～2010年1月来湖南省人民医院体检中心体检人群共4076例,排除过量饮酒者、乙肝标志物阳性者及相关资料不全者共2830例纳入本研究。其中1367例在1～3年后再次体检。记录受检者身高、体重、血压、血脂、空腹血糖、腹部B超结果。NAFLD采用2010年中华医学会肝病学分会诊断标准中影像学诊断定义,行腹部B超检查进行诊断。结果:1.我院体检人群中MHO合并NAFLD者占51.34%,明显高于正常对照组(P=0.000),MHO组发生NAFLD的OR值为19.967(95%CI,12.646-31.533;P=0.000)。2.随访1～3年后,MHO中NAFLD发病率高于正常对照组(44.44%vs 7.02%,OR=10.600,95%CI,4.873-23.058;P=0.000)。结论:MHO个体合并NAFLD比例较正常对照者升高,MHO个体增加NAFLD患病风险。     

胰岛素抵抗与脂肪肝关系的研究

胰岛素抵抗(IR)是许多疾病的独立危险因素。胰岛素抵抗与脂肪代谢紊乱非常密切,研究发现它在脂肪肝的发生、发展过程中起了很大的作用。近年来,越来越多的人已经意识到脂肪肝与胰岛素抵抗之间的密切关系。在胰岛素抵抗与脂肪肝的研究中关于瘦素及瘦素抵抗在胰岛素抵抗及脂肪肝的关系中的作用是研究比较多的,本文主要介绍了胰岛素抵抗、脂肪肝的发生机制及瘦素、瘦素抵抗在其中的催化作用。     

非酒精性脂肪性肝病与代谢综合征组分的相关性研究进展

非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)在全世界人群中发病率逐年上升,成为新的全球公共健康问题,已越来越引起临床关注。其发病以胰岛素抵抗为基础,与肥胖、血脂紊乱、原发性高血压、2型糖尿病等代谢综合征各组分密切相关。NAFLD可进展至肝硬化、肝衰竭甚至肝癌,伴有代谢综合征一种或多种组分可能加速疾病的进展。NAFLD初期是一种可逆性过程,充分了解影响其发生、发展的相关代谢危险因素并及时纠正,可能导致疾病的逆转或延缓其进程。本文就NAFLD与代谢综合征各组分的相关调查研究进行综述。     

非酒精性脂肪肝与脂肪性肝炎动物模型研究进展

非酒精性脂肪肝是无酒精滥用的包括单纯性脂肪肝、脂肪性肝炎、脂肪性肝纤维化和肝硬化的肝病综合征,目前已成为广受关注的肝病医学难题。随着抗脂肪肝药物的深入研究,动物模型制作得到很好发展。近年来,在大鼠、沙鼠、小鼠、兔和小猪等动物种属成功地建立了食物、胃肠外营养与蛋氨酸胆碱缺乏等诱导的单纯性脂肪肝和脂肪性肝炎动物模型,这些模型为研究脂肪肝和脂肪性肝炎的发病机理与治疗提供了机会。每种动物模型各有优缺点,合理应用动物模型能更好地开展脂肪肝病的实验和临床研究。本文综述了非酒精性脂肪肝及脂肪性肝炎动物模型制作方法的若干研究进展。     

Association between Serum Growth Hormone Levels and Nonalcoholic Fatty Liver Disease: A Cross-Sectional Study

Growth hormone (GH) is an important regulator of metabolism and body composition. GH deficiency is associated with increased visceral body fat and other features of the metabolic syndrome. Here we performed a cross-sectional study to explore the association of GH levels with nonalcoholic fatty liver disease (NAFLD), which is considered to be the hepatic manifestation of the metabolic syndrome. A total of 1,667 subjects were diagnosed as NAFLD according the diagnostic criteria, and 5,479 subjects were defined as the controls. The subjects with NAFLD had significantly lower levels of serum GH than the controls. Those with low GH levels had a higher prevalence of NAFLD and the metabolic syndrome. A stepwise logistic regression analysis showed that GH levels were significantly associated with the risk factor for NAFLD (OR = 0.651, 95%CI = 0.574–0.738, P<0.001). Our results showed a significant association between lower serum GH levels and NAFLD.     

MicroRNAs in the Pathogenesis of Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD), or, more accurately, metabolic associated fatty liver disease, accounts for a large proportion of chronic liver disorders worldwide and is closely associated with other conditions such as cardiovascular disease, obesity, and type 2 diabetes mellitus. NAFLD ranges from simple steatosis to nonalcoholic steatohepatitis (NASH) and can progress to cirrhosis and, eventually, also hepatocellular carcinoma. The morbidity and mortality associated with NAFLD are increasing rapidly year on year. Consequently, there is an urgent need to understand the etiology and pathogenesis of NAFLD and identify effective therapeutic targets. MicroRNAs (miRNAs), important epigenetic factors, have recently been proposed to participate in NAFLD pathogenesis. Here, we review the roles of miRNAs in lipid metabolism, inflammation, apoptosis, fibrosis, hepatic stellate cell activation, insulin resistance, and oxidative stress, key factors that contribute to the occurrence and progression of NAFLD. Additionally, we summarize the role of miRNA-enriched extracellular vesicles in NAFLD. These miRNAs may comprise suitable therapeutic targets for the treatment of this condition.     

非酒精性脂肪性肝病蛋白质组学研究进展

非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)是一种常见慢性肝脏疾病,其发病率呈逐年上升趋势,但发病机制尚未明确,诊疗手段仍不完善.蛋白质组学(proteomics)的出现使NAFLD研究有了进一步的发展,相关研究已达21个.目前,蛋白质组学技术可以研究疾病相关的分子改变,从而寻找新的生物标志物和治疗靶标.在此,对蛋白质组学在NAFLD诊断及分期、发病机制和其他相关领域研究进展作一个较为全面的综述.首先,对研究中遇到的研究对象、样本种类、实验方法和标志物特征选择进行经验性总结.其次,除了介绍如何运用蛋白质组学研究病因、危险因素和重要分子在NAFLD发病机制中的作用,还介绍NAFLD发病机制的亚细胞蛋白质组学、修饰蛋白质组学以及蛋白质组学与转录组学相结合的研究实例.此外,对差异蛋白质的分析策略和价值作了重点阐述,收集到一些有望成为NAFLD治疗靶标的候选分子.最后,结合新技术展望研究新空间,以期能够有助于推动蛋白质组学在寻找新的疾病标志物、探索疾病分子机制和治疗靶标中开辟新的途径.     

非酒精性脂肪性肝病的药物治疗进展

非酒精性脂肪性肝病已日渐成为目前慢性肝病的主要病因,其与肥胖、2型糖尿病和代谢综合征等疾病密切相关,疾病谱主要包括非酒精性单纯性脂肪肝、非酒精性脂肪性肝炎和肝硬化。早期诊断和及时治疗可望减轻NAFLD患者肝炎的严重程度并延缓肝纤维化的进展,减少并发症的出现。目前认为其发病与胰岛素抵抗、氧化应激及脂质过氧化和肠道菌群失调等因素有关。通过饮食调整和适当运动而减轻体重被认为是最基础的治疗措施,但单纯依靠减肥治疗脂肪性肝病(FLD)的效果并不理想,药物在脂肪性肝炎防治中的作用同样不可忽视。目前没有根治这一疾病的特效药物,单纯针对某一发病机制的药物亦难以治愈NAFLD这种复杂的疾病,本文主要从改善胰岛素抵抗、降脂、保肝抗炎及改善肠道菌群等四方面介绍一下本病的药物治疗进展。提倡改变生活方式的非药物治疗与药物干预治疗紧密结合,以取得最理想的治疗效果。     

Genetics of Nonalcoholic Fatty Liver Disease:An Overview

Nonalcoholic fatty liver disease(NAFLD) is the most common liver disease in the world today.Its incidence in adults and children is rising rapidly due to the ongoing epidemics of obesity and type 2 diabetes.Hence,it has become a global public health issue.Environmental factors have been found to play a major role in the etiology of NAFLD,especially for genetically susceptible populations. Among these,one of the most important factors is junk food,especially the typical "Western-style" diet rich in simple carbohydrates, saturated fat,and highly processed food materials.Genetic predisposition to NAFLD does occur;however,a precise definition of genetic factors responsible for NAFLD is still lacking.Specific variants of different genes have been shown to present a risk for NAFLD.Genetic studies might be helpful in the management of the disease by developing novel treatment strategies based on individual’s genotype.     

Association between Serum Atypical Fibroblast Growth Factors 21 and 19 and Pediatric Nonalcoholic Fatty Liver Disease

Atypical fibroblast growth factors (FGF) 21 and 19 play a central role in energy metabolism through the mediation of Klotho coreceptor. Contradictory findings are available about the association of FGF21 and FGF19 with nonalcoholic fatty liver disease (NAFLD) in humans. We investigated the association of serum FGF21, FGF19 and liver Klotho coreceptor with non-alcoholic steatohepatitis (NASH) and fibrosis in children with NAFLD. Serum FGF21 and FGF19 were measured in 84 children with biopsy-proven NAFLD and 23 controls (CTRL). The hepatic expression of Klotho coreceptor was measured in 7 CTRL, 9 patients with NASH (NASH+) and 11 patients without NASH (NASH−). FGF21 and FGF19 showed a tendency to decrease from CTRL (median FGF21 = 196 pg/mL; median FGF19 = 201 pg/mL) to NASH− (FGF21 = 89 pg/mL; FGF19 = 81 pg/mL) to NASH+ patients (FGF21 = 54 pg/mL; FGF19 = 41 pg/mL) (p<0.001 for all comparisons) and were inversely associated with the probability of NASH and fibrosis in children with NAFLD. The hepatic expression of Klotho coreceptor was inversely associated with NASH (R² = 0.87, p<0.0001) and directly associated with serum FGF21 (R² = 0.57, p<0.0001) and FGF19 (R² = 0.67, p<0.0001). In conclusion, serum FGF19 and FGF21 and hepatic Klotho expression are inversely associated with hepatic damage in children with NAFLD and these findings may have important implications for understanding the mechanisms of NAFLD progression.     

Systems Approaches to Biology and Disease Enable Translational Systems Medicine

The development and application of systems strategies to biology and disease are transforming medical research and clinical practice in an unprecedented rate.In the foreseeable future,clinicians,medical researchers,and ultimately the consumers and patients will be increasingly equipped with a deluge of personal health information,e.g.,whole genome sequences,molecular profiling of diseased tissues,and periodic multi-analyte blood testing of biomarker panels for disease and wellness.The convergence of these practices will enable accurate prediction of disease susceptibility and early diagnosis for actionable preventive schema and personalized treatment regimes tailored to each individual.It will also entail proactive participation from all major stakeholders in the health care system.We are at the dawn of predictive,preventive,personalized,and participatory(P4) medicine,the fully implementation of which requires marrying basic and clinical researches through advanced systems thinking and the employment of high-throughput technologies in genomics,proteomics,nanofluidics,single-cell analysis,and computation strategies in a highly-orchestrated discipline we termed translational systems medicine.     

非酒精性脂肪性肝病大鼠肝脏PPAR-γ的表达

目的:研究PPAR-Y在非酒精性脂肪性肝病(NAFLD)大鼠肝脏组织中的表达,探讨非酒精脂肪性肝病可能的发病机制.方法:雄性SD大鼠30只,随机分为A(正常组)15只普通饮食,B(高脂组)15只高脂饮食.8周后,自两组各随机抽取2只大鼠处死,光镜观察证实脂肪肝造模成功,继续喂养4周后处死所有大鼠,取血清做免疫生化检查,取肝组织标本,分别以光镜观察做出NAS评分,免疫组化和PCR法检测肝组织PPAR-Y蛋白的表达.结果:1.高脂饮食可以成功的复制NAFLD的大鼠模型;2.血清GLU、TC、TG、HDL-C、LDLC在高脂组表达量较正常组明显升高,差异具有统计学意义(P＜0.05);3.免疫组化显示:高脂组PPAR-Y表达量较正常组升高;结论:1.高脂饮食可成功复制NAFLD模型;2.PPAR-Y在NAFLD大鼠肝脏成脂性改变中具有重要作用.     

非酒精性脂肪性肝病大鼠肝脏PPAR-γ的表达

目的：研究PPAR-γ在非酒精性脂肪性肝病（NAFLD）大鼠肝脏组织中的表达,探讨非酒精脂肪性肝病可能的发病机制。方法：雄性SD大鼠30只,随机分为A（正常组）15只普通饮食,B（高脂组）15只高脂饮食。8周后,自两组各随机抽取2只大鼠处死,光镜观察证实脂肪肝造模成功,继续喂养4周后处死所有大鼠,取血清做免疫生化检查,取肝组织标本,分别以光镜观察做出NAS评分,免疫组化和PCR法检测肝组织PPAR-γ蛋白的表达。结果：1.高脂饮食可以成功的复制NAFLD的大鼠模型;2.血清GLU、TC、TG、HDL-C、LDL-C在高脂组表达量较正常组明显升高,差异具有统计学意义（P〈0.05）;3.免疫组化显示：高脂组PPAR-γ表达量较正常组升高;结论：1.高脂饮食可成功复制NAFLD模型;2.PPAR-γ在NAFLD大鼠肝脏成脂性改变中具有重要作用。     

非酒精性脂肪性肝病的发病机制及治疗进展

近年来,随着人们生活水平的提高,脂肪性肝病的发病率明显上升,且患病年龄趋于低龄化,已经成为严重危害我国人民健康的常见疾病,我国非酒精性脂肪性肝病的发病率明显高于酒精性脂肪性肝病。本文主要对NAFLD的发病机制及相关治疗进展做简要的综述。NAFLD的发病机制与胰岛素抵抗、氧化应激、代谢综合征、脂肪细胞因子的作用、内质网应激、及铁超载等多种因素有关。NAFLD的治疗可以从防治原发病或相关危险因素、基础治疗(行为或生活方式干预;调整饮食;运动疗法)、药物治疗以及手术治疗等方面进行。了解国际上NAFLD的发病机制以及相关治疗进展,对遏制非酒精性脂肪性肝病的发生、发展趋势有着十分重要的意义。     

Correlates and Heritability of Nonalcoholic Fatty Liver Disease in a Minority Cohort

Nonalcoholic fatty liver disease (NAFLD) is associated with obesity and insulin resistance. The condition disproportionately affects Hispanic Americans. The aims of this study were to examine the risk factors and heritability of NAFLD in 795 Hispanic American and 347 African‐American adults participating in the Insulin Resistance Atherosclerosis Study (IRAS) Family Study. Computed tomography (CT) scans of the abdomen were evaluated centrally for measures of liver–spleen (LS) density ratio and abdominal fat distribution. Other measures included insulin sensitivity (S_I) calculated from a frequently sampled intravenous glucose tolerance test and various laboratory measures. Statistical models which adjust for familial relationships were estimated separately for the two ethnic groups. Heritability was calculated using a variance components approach. The mean age of the cohort was 49 years (range 22–84); 66% were female. NAFLD (LS ratio <1) was more common in Hispanic Americans (24%) than African Americans (10%). NAFLD was independently associated with S_I and visceral adipose tissue (VAT) area in both ethnic groups, although the proportion of explained variance was considerably higher in the Hispanic models. Adiponectin contributed significantly in the African‐American models whereas triglycerides (TGs) and plasminogen activator inhibitor 1 (PAI‐1) contributed only in the Hispanic models. Liver density was modestly heritable in both ethnic groups (h² ～0.35). In summary, the prevalence of NAFLD was twofold greater in Hispanic than African Americans. Certain correlates of NAFLD were similar between the ethnic groups, whereas others were distinct. NAFLD was modestly heritable. These findings suggest that NAFLD may have a differing environmental and/or genetic basis in these ethnic groups.