Metabolic syndrome from the view point of public health: with special reference to nonalcoholic fatty liver disease

Changes in human behavior and lifestyle over the last century have resulted in a dramatic increase in the incidence of obesity, type 2 diabetes, and the metabolic syndrome. Differences in the reported overall prevalence of the metabolic syndrome, which is generally in the range of 10-30% depend on the diagnostic criteria and subjects of the study. Recently, Japanese criteria for diagnosis of the metabolic syndrome were defined. With these criteria, presence of visceral obesity is essential for the diagnosis and is simply determined by measurement of waist circumference. Reflecting a dramatic increase in the incidence of obesity and type 2 diabetes, the incidence of the metabolic syndrome is increasing in Japan as well as in Western countries, regardless of the criteria applied. Recently, the number of workers with elevated liver enzymes, in whom virus hepatitis, alcoholic liver disease, drug induced hepatitis, autoimmune hepatitis, and iron overload were ruled out as causal agents, has also be found to be increasing at workplace health checkups. Most of such workers have components of the metabolic syndrome and the presence of steatosis in the liver, this pathologic condition now being termed nonalcoholic fatty liver disease (NAFLD). In this review, we describe the relationship between NAFLD and the metabolic syndrome.     

The metabolic syndrome and nonalcoholic fatty liver disease

Accumulating evidence supports an association between nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome, diabetes, and obesity. The epidemiology, pathogenesis, and approach to treatment of NAFLD follow the same trends as these other metabolic disorders, and insulin resistance is the key event linking NAFLD to these diseases. The impairment in fat and glucose metabolism that ensues once insulin resistance occurs leads to similar biochemical and clinical abnormalities in patients with NAFLD. Many recent studies investigating the cellular and genetic basis of these diseases have led to a better understanding of their pathogenesis and insight into treatment and management. The most effective treatment thus far is weight loss and the use of insulin-modulating pharmacologic agents. A few additional treatment strategies include the use of lipid-lowering, antioxidants or cytoprotective agents, but there is no single therapeutic approach that is effective for managing NAFLD. Future therapies may combine drugs that target specific pathways involved in NAFLD pathogenesis.     

非酒精性脂肪性肝病与代谢综合征相关性研究

目的 分析非酒精性脂肪性肝病(NAFLD)与MS的相关性.方法 2010-2011年对武汉大学医院在校教职工体检包括询问病史、体格检查、生化检查、肝脏彩超检查.按NAFLD诊断标准将研究对象分为NAFLD组和非NAFLD组,对两组与MS及其相关因素进行比较分析.结果 (1) NAFLD总患病率为20.7％,MS为13.3％,NAFLD组BMI、SBP、DBP、TG、FPG均较非NAFLD组高,HDL-C水平低于非NAFLD组(P＜0.001).(2)NAFLD组MS患病率、肥胖患病率、高血糖异常率、高血压率、血脂异常率均高于非NAFLD组,且差异有统计学意义(P＜0.001).(3)NAFLD组具有1～4个MS诊断指标的风险是非NAFLD组的1.66、4.22、8.72和25.62倍,差异均有统计学意义(P＜0.001).结论 武汉大学教职工体检人群中NAFLD患者的MS及其危险因素发生率均高于非NAFLD患者,NAFLD与MS密切相关.     

非肥胖的糖耐量受损者的非酒精性脂肪性肝病与代谢综合征的关系

目的探讨非肥胖的糖耐量受损(IGT)者的非酒精性脂肪性肝病(NAFLD)与代谢综合征(MS)的关系。方法126例非肥胖的IGT者,根据B超诊断有无NAFLD分为IGT伴NAFLD组64例,IGT不伴NAFLD组62例。对两组患者的体重指数(BMI)、血压、血糖、血脂、血胰岛素、稳态模型评估法胰岛素抵抗指数(HOMA-IRI)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)及MS患病率等指标进行比较分析,并对NAFLD与上述指标的关系进行多因素的Logistic回归分析。结果IGT伴NAFLD组的BMI、空腹血糖、甘油三酯、胰岛素、HOMA-IR、ALT、AST及MS患病率较IGT不伴NAFLD组显著增高,而且NAFLD与MS及HOMA-IR呈独立相关。结论在非肥胖的IGT者中NAFLD与MS独立相关。MS不但明显增加NAFLD的发生率,而且还加重肝脏损害。     

非酒精性脂肪肝的基因研究

非酒精性脂肪肝（NAFLD）的发病率及脂肪性肝炎（NASH）的发生率与种族、民族和家族密切相关。脂肪性肝病是一组遗传-环境-代谢应激相关性的疾病,近年来NAFLD与遗传和基因的关系越来越受到人们的重视,研究NAFLD的基因应从肥胖、脂肪酸代谢、胰岛素抵抗等与NAFLD有关的环节的相关基因着手。     

中国非酒精性脂肪性肝病的流行病学

非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)是西欧、美国、澳大利亚、日本第一大慢性肝病以及肝酶异常的首要病因,普通成年人NAFLD患病率为20%～33%~([1-3]),其中10%～15%为非酒精性脂肪性肝炎(NASH),后者10年内肝硬化发生率为15%～25%,而脂肪性肝硬化患者发生原发性肝细胞癌、肝衰竭和移植肝复发的概率为30%～40%.     

非酒精性脂肪性肝病超声诊断

以非酒精性脂肪性肝病(NAFLD)为代表的代谢性脂肪性肝炎,系以内脏脂肪蓄积为关键介质导致的肝脏炎性反应和纤维化[1].本病的超声影像表现为肝脏脂肪累积和肝细胞脂肪交性的非特异性反应,当肝脏脂肪累积>5%时便可显示脂肪肝声像而资为超声诊断依据.实践证明,现代超声诊断技术便捷于粗略评价脂肪肝.因其操作简便,费用相对低廉,加之无损伤、非介入性特点,被检患者乐于接受,而首选适用于广大代谢综合征人群之筛检.     

非肥胖的高血压病患者的非酒精性脂肪肝与代谢综合征的关系

目的探讨非肥胖的不伴有糖尿病的高血压病患者的非酒精性脂肪肝（NAFLD）与代谢综合征（MS）的关系。方法84例非肥胖的不伴有糖尿病的高血压病患者,根据B超诊断有无脂肪肝分为高血压伴NAFLD组42例,高血压不伴NAFLD组42例。对2组患者的体重指数（BMI）、血压、血糖、血脂、血胰岛素、胰岛素抵抗指数（HOMA-IR）、转氨酶及MS患病率等指标进行比较分析,并对MS与上述指标的关系进行多因素的logistic回归分析。结果高血压伴NAFLD组的BMI、甘油三酯、胰岛素、HO-MA-IR、转氨酶及MS患病率较不伴NAFLD组显著增高,而且MS与NAFLD呈独立相关。结论MS不但明显增加NAFLD发生率,而且还加重肝脏损害。     

熊去氧胆酸治疗非酒精性脂肪性肝病临床研究

目的探讨熊去氧胆酸治疗非酒精性脂肪性肝病（NAFLD）的疗效及安全性。方法将纳入标准的114例NAFLD患者随机分为两组：对照组给予饮食控制，同时给予益肝灵片（2片／次，日3次口服）；治疗组在对照组的基础上，加用熊去氧胆酸片（2片／次，日3次口服）；两组疗程均为12周。治疗前后测定血清丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、甘油三酯（TG）、总胆固醇（TC）。结果治疗组ALT、AST、TG、TC改善明显高于对照组，差异有统计学意义（P〈0．05）。治疗组总有效率为88．9％，明显高于对照组的63．3％（P〈0．05）。结论熊去氧胆酸可安全有效地用于NAFLD的治疗。     

熊去氧胆酸治疗非酒精性脂肪性肝病临床研究

目的探讨熊去氧胆酸治疗非酒精性脂肪性肝病(NAFLD)的疗效及安全性。方法将纳入标准的114例NAFLD患者随机分为两组对照组给予饮食控制,同时给予益肝灵片(2片/次,日3次口服);治疗组在对照组的基础上,加用熊去氧胆酸片(2片/次,日3次口服);两组疗程均为12周。治疗前后测定血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、甘油三酯(TG)、总胆固醇(TC)。结果治疗组ALT、AST、TG、TC改善明显高于对照组,差异有统计学意义(P<0.05)。治疗组总有效率为88.9%,明显高于对照组的63.3%(P<0.05)。结论熊去氧胆酸可安全有效地用于NAFLD的治疗。     

非酒精性脂肪性肝病与动脉粥样硬化的关系

目的探讨非酒精性脂肪性肝病与动脉粥样硬化的关系及可能机制。方法122例门诊及住院患者根据B超检查结果分为2组,非酒精性脂肪性肝病组62例和正常对照组60例,对2组患者的动脉粥样硬化情况及其相关因素进行分析。结果非酒精性脂肪性肝病组BMI、腰臀比值、收缩压、舒张压、空腹血糖、胰岛素浓度、高密度脂蛋白、廿油三酯、高敏C反应蛋白、胰岛素抵抗指数及比例、谷丙转氨酶、谷草转氨酶和γ-氨酰转肽酶水平与对照组比较差异有统计学意义（P〈0．001）;总胆固醇、低密度脂蛋白、脂蛋白A两组水平相似;非酒精性脂肪性肝病组颈动脉斑块检出率和颈动脉内膜中层厚度均高于正常对照组,差异有统计学意义（P〈0．05）。经多变量分析发现,非酒精性脂肪性肝病和IMT及斑块呈显著相关（OR8．3,95％CI1．2～7．7,P=0．001）。结论非酒精性脂肪性肝病患者动脉粥样硬化的患病率高于正常对照组,非酒精性脂肪性肝病为动脉粥样硬化的危险因素,机制可能与内脏性肥胖、胰岛素抵抗和非酒精性脂肪性肝病状态下增加的氧化应激特性及血脂紊乱、炎症反应有关。     

大豆异黄酮对非酒精性脂肪肝大鼠肝脏脂代谢的影响

目的 研究大豆异黄酮对非酒精性脂肪肝(NAFLD)大鼠肝脏脂质、血脂、抗氧化指标及肝脏脂肪代谢相关因子的影响.方法 将36只雄性SD大鼠用随机数字表法按体重分层随机分为正常对照组、NAFLD模型对照组、大豆异黄酮低剂量组(10 mg/kg)及高剂量组(20 mg/kg),每组9只.正常对照组采用D12450B饲料(10%脂肪热能),模型对照组和大豆异黄酮干预组采用D12492饲料(60%脂肪热能),喂养12周后,检测各组大鼠肝脏脂质、血脂和抗氧化指标的变化,Western blotting检测大鼠肝组织中固醇调节原件结合蛋白-1c(SREBP-1c)、脂肪酸合成酶(FAS)和过氧化物酶体增殖物激活受体α(PPARα)的蛋白表达.结果 正常对照组、NAFLD模型对照组、大豆异黄酮低剂量组、高剂量组肝脏甘油三酯(TG)分别为(8.11±4.13)、(57.06±16.95)、(31.26±10.48)、(31.38±13.25)mmol/mg蛋白(F=22.569,P＜0.01);肝脏游离脂肪酸(FFA)分别为(0.030±0.007)、(0.042±0.009)、(0.038±0.009)、(0.032±0.005)μmol/mg蛋白(F=4.857,P＜0.01);肝脏超氧化物歧化酶(SOD)活性分别为(502.29±23.71)、(201.83±16.99)、(228.93±21.71)、(238.08±15.96)U/mg蛋白(F=9.555,P＜0.01);肝脏丙二醛(MDA)含量分别为(1.29±0.29)、(2.85±0.73)、(2.07±0.49)、(2.03±0.37)nmol/mg蛋白(F=13.449,P＜0.01);肝脏SREBP-1c蛋白表达分别为0.45±0.16、1.42±0.30、1.02±0.31、0.47±0.27(F=24.515,P＜0.01);FAS蛋白表达分别为0.27±0.08、1.97±0.47、1.35±0.30、0.49±0.12(F=60.361,P＜0.01);PPARα蛋白表达分别为2.03±0.56、0.41±0.17、0.81±0.27、0.66±0.16(F=37.97,P＜0.01).结论大豆异黄酮可能通过抑制SREBP-1 c、激活PPARα的表达来减少肝脏脂质沉积,增加抗氧化能力.

Abstract：

Objective To study the effects of soybean isoflavone on liver lipid,serum lipid,antioxidant index and hepatic lipid metabolism associated factors in nonalcoholic fatty liver rats.Methods Thirty-six male rats(SD)were randomly divided into four groups by weight: normal control group,nonalcoholic fatty liver disease(NAFLD) model control group,low-dose isoflavone treatment group (10 mg/kg)and high-dose isoflavone group(20 mg/kg),9 rats in each group.Normal control rats were fed with D12450B(10% fat energy),model control and isoflavone intervention rats were fed with D12492(60%fat energy).Twelve weeks later,liver lipid,serum lipid and antioxidant index were observed.Liver sterol regulatory element binding protein-1 c(SREBP-1 c),fatty acid synthase(FAS)and Peroxisome proliferators activated receptor alpha(PPAR alpha)were detected by western blotting.Results Liver triglyceride(TG)in normal control group,NAFLD model control group,low-dose isoflavone group and high-dose isoflavone group were(8.11 ± 4.13),(57.06 ± 16.95),(31.26 ± 10.48),(31.38 ± 13.25)mmol/mg protein,respectively(F = 22.569,P ＜0.01); liver free fatty acid(FFA)were(0.030 ± 0.007),(0.042 ± 0.009),(0.038 ± 0.009),(0.032 ± 0.005)μmol/mg protein,respectively(F = 4.857,P ＜0.01); liver superoxide dismutase(SOD)activity were(502.29 ± 23.71),(201.83 ± 16.99),(228.93 ± 21.71),(238.08 ±15.96)U/mg protein,respectively(F = 9.555,P ＜0.01); liver malondialdehyde(MDA)were(1.29 ±0.29),(2.85 ± 0.73),(2.07 ± 0.49),(2.03 ± 0.37)nmol/mg protein,respectively(F = 13.449,P ＜0.01);SREBP-1 c protein expression were 0.45 ± 0.16,1.42 ± 0.30,1.02 ± 0.31,0.47 ± 0.27,respectively (F=24.515,P＜0.01);FAS protein expression were 0.27 ±0.08,1.97 ±0.47,1.35-0.30,0.49 ±0.12,respectively(F = 60.361,P ＜0.01); PPARα protein expression were 2.03 ± 0.56,0.41 ± 0.17,0.81 ±0.27,0.66±0.16,respectively(F=37.97,P＜0.01).Conclusion Soy isoflavone can reduce the hepatic lipid deposition and increase antioxidant capacity,the mechanism may be related to inhibition of SREBP-1c and activation of PPARα expression in liver.     

超重肥胖儿童非酒精性脂肪肝病与代谢综合征相关性研究

【目的】了解超重肥胖儿童非酒精性脂肪肝病(nonalcoholic fatty liver disease,NAFLD)中代谢综合征(metabolic syndrome,MS)的发病情况,探讨NAFLD与MS的相互关系。【方法】对212例超重肥胖儿童进行体格测量、血液生化检测和肝脏超声检查,分析NAFLD与MS的关系。【结果】共检出NAFLD患儿109例,MS 64例。腹型肥胖、高血糖、血脂紊乱、高血压、NAFLD和MS的检出率分别为85.8%、12.7%、57.1%、35.4%、51.4%和30.2%。与无NAFLD的103例相比,两组在体质指数、甘油三酯、稳态模型胰岛素抵抗指数(Homa-IR)和敏感指数(Homa-IAI)以及MS组分数等方面差异有高度统计学意义(P0.001)。腹型肥胖、高血糖、血脂紊乱、高血压发生NAFLD的比值比(OR)分别是非NAFLD组的2.168、2.348、2.145、2.418倍,而MS患者患NAFLD的风险最高(OR=3.109)。109例NAFLD患者中,108例存在1项或多项代谢紊乱,所有代谢紊乱都具有者15例(13.8%)。【结论】超重肥胖儿童NAFLD伴发MS较普遍,NAFLD与MS及其组分密切相关,是儿童MS在肝脏的表现。     

非酒精性脂肪性肝病发病机制进展

非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)是一种遗传-环境-代谢应激相关性疾病,代谢紊乱、氧化应激及细胞因子等多种因素共同作用导致肝脏的脂质合成与排泄失衡,肝细胞内脂肪蓄积,进而发展为非酒精性脂肪性肝炎(nonalcoholic steatohepatitis,NASH)和肝硬化.     

非酒精性脂肪性肝病患者脂联水平检测及意义

目的 检测非酒精性脂肪性肝病(NAFLD)患者血清脂联素的水平并探讨其临床意义.方法 选取60例无糖尿病的NAFLD患者(NAFLD组)和40例健康对照者(对照组),测定两组的空腹血糖、血脂、胰岛素和脂联素水平,计算稳态模型评估法胰岛素抵抗指数(HOMA-IRI).结果 NAFLD组血清脂联素水平明显低于对照组[(8.04±3.20)μg/ml比(12.53±8.50)μg/ml,P＜0.001];脂联素与体重指数(BMI)、腰围、天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、γ-谷氨酰基转移酶(GGT)、甘油三酯(TG)、HOMA-IRI呈负相关;BMI、HOMA-IRI为脂联素水平的独立影响因素.结论 NAFLD患者血清脂联素水平降低,脂联素可能参与了NAFLD患者胰岛素抵抗及动脉粥样硬化的发病过程.     

Therapeutic potential of green tea in nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is a constellation of progressive liver disorders that are closely related to obesity, diabetes, and insulin resistance and may afflict over 70 million Americans. NAFLD may occur as relatively benign, nonprogressive liver steatosis, but in many individuals it may progress in severity to nonalcoholic steatohepatitis, fibrosis, cirrhosis, and liver failure or hepatocellular carcinoma. No validated treatments currently exist for NAFLD except for weight loss, which has a poor long-term success rate. Thus, dietary strategies that prevent the development of liver steatosis or its progression to nonalcoholic steatohepatitis are critically needed. Green tea is rich in polyphenolic catechins that have hypolipidemic, thermogenic, antioxidant, and anti-inflammatory activities that may mitigate the occurrence and progression of NAFLD. This review presents the experimental evidence demonstrating the hepatoprotective properties of green tea and its catechins and the proposed mechanisms by which these targeted dietary agents protect against NAFLD.     

Pathways underlying iron accumulation in human nonalcoholic fatty liver disease

BACKGROUND: Mild iron overload is frequently observed in nonalcoholic fatty liver disease (NAFLD). OBJECTIVE: We aimed to study putative pathways underlying iron accumulation in NAFLD. DESIGN: Hepatic and duodenal expression of critical iron molecules in NAFLD patients with (n = 32) and without (n = 29) iron overload, hereditary hemochromatosis (n = 10), and controls (n = 20) were investigated. Phlebotomy treatment was performed in 14 NAFLD patients. RESULTS: The hepatic expressions of the iron-export protein ferroportin-1 (FP-1) and of the iron-sensing molecule hemojuvelin (HJV) were significantly lower in NAFLD patients. The mRNA expression of the iron-regulatory peptide hepcidin was increased in NAFLD patients with iron overload, which was paralleled by low duodenal FP-1 expression. Hepatic mRNA and serum protein concentrations of tumor necrosis factor-alpha (TNF-alpha) were increased in NAFLD patients and were inversely correlated with both liver FP-1 and HJV mRNA and positively associated with body mass index and hepatic hepcidin mRNA. Accordingly, TNF-alpha inhibited the FP-1 and HJV mRNA formation in HepG2 cells. Phlebotomy treatment of NALFD patients reduced serum ferritin, transferrin saturation, and TNF-alpha concentrations and improved liver function tests. CONCLUSIONS: Iron accumulation in NAFLD may result from an impaired iron export due to down-regulation of FP1 and ineffective hepatic iron sensing, as indicated by low HJV expression. TNF-alpha appears to play a role in exerting these regulatory changes. Increased hepcidin formation in iron-overloaded NAFLD patients, however, results in decreased duodenal FP-1 expression, whereas a reduction in liver FP-1 may perpetuate hepatic iron retention. Phlebotomy offers a safe and efficient therapy for these metabolic disturbances.