| Introduction:Non alcoholic fatty liver disease (NAFLD) is emerging as the most common chronic liver condition fn the Western world. It is associated with insulin resistance and frequently occurs with features of the metabolic syndrome. Disease presentation ranges from asymptomatic elevated liver enzyme levels to cirrhosis with complications of liver failure and hepatocellular carcinoma. The diagnosis of nonalcoholic fatty liver disease requires evidence of fatty changes in the liver in the absence of a history of excessive alcohol consumption. The histologic spectrum of NAFLD spans from generally benign, bland steatosis to steatosis with evidence of hepatocellular inflammation and damage (nonalcoholic steatohepatitis, or NASH), which may be complicated by progressive f ibrosis and cirrhosis. Ultrasonography detects fatty changes in the liver is 10%-23% of western world. But the epidemiologic data in our country were still unknowm. Our aims were to realize the epidemiologic conditions in Hangzhou, and to investigate the risk factors of NAFLD.There is increasing evidence that visceral adipose tissue is a causative risk factor for fatty liver and nonalcoholic steatohepatitis. Adipose tissue-derived secretory proteins are collectively named adipocytokines, which mediate many of the vascular and metabolic complications of adiposity. The growing epidemic of obesity has led to many studies on the role of adipose tissue as an endocrine organ. Obesity and mainly visceral fat accumulation impair adipocyte function and adipocytokinesecretion and the altered release of these proteins contributes to insulin resistance.Leptin is a product of obese gene which regulates food intake and energy expenditure. Moreover, it is involved in the homeostasis of body composition and is linked to the regulation of insulin signaling, thus playing an important role in liver fat storage. In order to elucidate leptin in nonalcoholic fatty liver disease, we evaluated its serum levels in patients with nonalcoholic fatty liver and normal group.Adiponectin is secreted from adipose tissue, and serum levels are markedly reduced in obesity. Adiponectin levels are negatively correlated with body fat percent, central fat distribution, fasting plasma insulin, oral glucose tolerance. It has two receptors;adipoRl is abundantly expressed in skeletal muscle and at moderate levels in other tissues, whereas adipoR2 rs predominantly expressed in the liver. Adiponectin is a hepatic insulin sensitizer and also an inhibitor of tumor necrosis factor and therefore we studied its levels in nonalcoholic fatty liver disease and compared the results with healthy volunteers and looked for the effect of gender on adiponectin levels.Human resistin, a 12. 5-kDa protein, contains 108 amino acids as a prepeptide, and its hydrophobic signal peptide is cleaved before its secretion. Resistin circulates in human blood as a dimeric protein consisting of two 92-amino acid polypeptides that are linked by a disulf ide bridge at Cys-26. Very little is known about the potential function of resistin. Thiazoladinedone drugs reduce insulin resistance and are used to treat type II diabetes. These drugs suppress the production of resistin byadipocytes, and their antidiabetes effects may, at least in part, be achieved through this mechanism.Serum levels of adiponectin and resistin were detected in NAFLD group and normal group in order to realize the function of adiponectin and resistin in the pathogenesis of NAFLD.Genetic variations in the leptin receptor gene have been conceived to affect obesity in general populations. Fatty liver disease is most common in obesity. The aims of section four of our experiments were to investigate whether leptin receptor LyslO9Arg and Arg223Gln polymorphism influences fatty liver disease and to assess the role of leptin receptor LyslO9Arg and Arg223Gln polymorphism in clinical parameters of subjects with fatty liver disease and healthy.Methods:1. studies of nonalcoholic fatty liver disease and risk factorsWe studied 2713 institutional employee who "take part in health physical examination during September to November in 2002 in The First Affiliated Hospital, College of Medicine, Zhejiang University. Its comprised 1171 males and 1542 females, the average age is 42. Everybody was inquired with their medical interview and history of alcoholic consumption. We measured their blood pressure, height, weight, waist circumference , hip circumference, abdominal wall fat thickness, percentage of body fat, B~mode ultrasonography of liver, and fasting blood glucose(FBS), hepatic function, serum lipid, HbsAg. The percent of body fat was measured by body composition analyzer from TANITA.All data were expressed as mean+SD. For the comparison of group means between nonalcoholic fatty liver disease group and control group, t-test was used as appropriate method with software spsslO.0. We used Logistic regression to assess the relationships between NAFLD and other 20 variables with software SPSS 10. 0.2. The relationships between NAFLD and serm leptinWe had chosen 196 individuals from those peoples who participated health examination. All subjects were divided into three groups by the diagnosis of B-mode ultrasonography, including normal liver group(50 individuals, including 22 men and 28 women), mild fatty liver group(48 individuals, including 28 men and 20 women) and severe fatty liver group(98 individuals, including 53 men and 45 women). Seven parameters, including body mass index, the percentage of body fat, GPT, triglyceride(TG)-, total cholesterol (TCH), high density lipoprotein(HDL), were examined in all subjects. All subjects were inquired of their consumption of alcohol.The percent of body fat was measured by body composition analyzer from TANITA. Serum leptin levels were assessed by means of radioimmunoassay. ALT, TC, TCH, LDH were assessed by enzyme immunoassay.All data were expressed as mean±SD. For the comparison of group means, t-test was used as appropriate method with spsslO. 0 software. We used bivariate correlate analysis to assess the relationships among nonalcoholic fatty liver disease, surum leptin, body mass index, the percentage of body fat, GPT, TG, TCH, HDL.3. The relationships among NAFLD, adiponectin and resistin43 patients with nonalcoholic fatty liver disease and 43 healthy adults were enrolled in this pair-matching study. Body height, body weight, abdominal wall fat thickness, waist circumference, hip circumference and the percentage of body fat were measured and serum adiponectin and resistin were determined in all individuals.Serum resistin levels were assessed by enzyme immunoassay and adiponectin levels were detected by ELISA. The test kits came from American Phonx Pharmaceuticals.All data were expressed as mean±SD. For the comparison of group means, paired samples t-test were used as appropriate method with spsslO. 0 software. We usedbivariate correlate analysis to assess the relationships among nonalcoholic fatty liver disease, surum adiponectin, resistin, body mass index, the percentage of body fat, abdominal wall fat thickness, wait/hip circumference, GPT, TG, TCH, HDL, FBS. 4. Evaluation of leptin receptor LyslO9Arg and Arg223Gln polymorphism180 blood samples were collected from subjects who received physical examination. BMI, hip, waist, blood pressure (BP), the percentage of body fat, total protein, albumin, ALT, triglyceride, cholesterol, HDL and fasting blood glucose were evaluated. Genomic DNA samples were extracted from blood and were used for the asymmetric PCR. Genotyping was performed using oligonucleotide microarray which fluorescence labeled PCR-Amplified fragments were hybridized to allele-specific oligonucleotide probes. The relevant mutation was confirmed by sequencing analysis of PCR product. Results: 1. Study of nonalcoholic fatty liver disease and risk factorsThere were 377 subject having nonalcoholic fatty liver disease, the incidence rate is 13.90%. It comprised 190 males, incidence rate 16. 23%, and 187 females, incidence rate 12.13%. And there were 5 peoples with nonalcoholic steatohepatitis, taking up 1. 33% of nonalcoholic fatty liver disease, the rest are simply nonalcoholic fatty liver disease. None of them had nonalcoholic fatty fibrosis or cirrhosis.From Logistic regression analysis, we found out that HDL is helpful factors. There were seven risk factors(abdomen wall fat thickness, triglyceride, fasting serum glucose, BMI, albumin, waist circumference, mean blood pressure).In NAFLD group, the age, waist circumference, hip, waist/hip, abdomen wall fat thickness, weight, BMI, percentage of body fat, mean blood pressure, total protein, albumin, GPT, TG, TC, FBS were higher than control group. HDL in NAFLD was lowerthan control group.2. The relationships between NAFLD and serm leptinThere were differences of BMI, the percentage of body fat, GPT, TG, TCH, HDL and leptin among groups. BMI, the percentage of body fat, GPT, TG, and leptin in mild fatty liver group(24. 58+2. 17, 28.76+5.48, 41.23+40.25, 2.07+1.31, 3.21 + 1.81) were higher than normal group (22. 13+2. 68, 26. 38+6. 24, 25.16+9. 57, 25.16+9. 57, 2.47+1.45). BMI, the percentage of body fat, GPT, TG, TCH, and leptin in sever fatty liver group(26. 06+2. 80, 32.54+6.67, 38.64+20.81, 2.29+1.12, 5.23+0.94, 4.37 +2. 59) were higher than normal group (22. 13+2.68, 26. 38+6.24, 25.16+9. 57, 25.16 +9. 57, 4. 75±0. 71, 2. 47+1. 45). BMI, the percentage of body fat and leptin in severe fatty liver group (26.06+2. 80, 32. 54+6. 67, 4. 37+2. 59) were higher than mild fatty liver group (24. 58+2.17, 28.76 + 5.48, 3.21 + 1.81).There was a positive collection between serum leptin and the percentage of body fat (p =0.606, ^7=0.000), TCH(p =0.215, p=0.003).We divided the severe fatty liver group into two groups(BMK25 group and BMI =>25group). The serum leptin levels in those two groups had not significant difference(BMK25 group 4.13+2.58 and BMI2*25group 4.53+2.61).3. The relationships among NAFLD, adiponectin and resistinThere were signicant differences in serum adiponectin levels in nonalcoholic fatty liver diseased. 38 + 0.65mg/L) and the control groups(2.01 + 1. lOmg/L) (t=2. 982, p<0. 01). Serum adiponectin concentration was significantly negatively correlated with abdomen circumference(P =-0.425), BMI(p =-0. 329), body fat%(p =-0.256), abdominal wall fat thickness( P =~0. 226), FBS( P =-0. 242). Whereas adiponectin levels were positively correlated with HDL(p =0. 226).There were signicant differences in serum resistin levels in nonalcoholic fattyliver disease(9.20 ± 7.20ng/L) and the control groups(4.70 ± 3.30mg/L) (t=-2.29, p<0.05). Serum resistin concentration was significantly positively correlated with waist circumference(p =0. 237). Whereas resistin levels had not relationships with blood pressure, FBS, TCH, TG, HDL. 4. Evaluation of leptin receptor LyslO9Arg and Arg223Gln polymorphismA total of 180 subjects (109 males and 71 females) with a mean age of 49. 97 years were included in the study, 117 of them were fatty liver diease and other 63 were healthy.LyslO9Arg : There are 144 (80%) subjects with GG genotype, 33(18.33%) with GA genotype and 3(1.67%) with AA genotype. The distribution of leptin receptor LyslO9Arg polymorphism was not significant (p>0. 05) between fatty liver disease (95GG, 21GA and 1AA) and healty subjects (49GG, 12GA and 2AA). The abdominal wall fat thickness is significantly higher in AA genotype (4.07+0.40 cm) than that in GG (2.72+0.74 cm) and GA genotype (2.79+0.63 cm) QK0.05). There were no significant difference in age, body mass index (BMI), hip, waist, blood pressure (BP), the percentage of body fat, total protein, albumin, ALT, triglyceride, cholesterol, HDL and fasting blood glucose between GG and GA genotype.Arg223Gln: There are 142 (78.89%) subjects with GG genotype and 38 (21. 11%) with GA genotype. AA genotype was not found. The distribution of leptin receptor Arg223Gln polymorphism was not significant (u=l. 19, p=0. 234) between fatty liver disease (89 GG and 28GA) and healthy subjects(53GG and 10GA). There were no significant difference in age, height, weight, BMI, the abdominal wall fat thickness, hip, waist, blood pressure, the percentage of body fat, total protein, albumin, ALT, triglyceride, cholesterol, HDL and fasting blood glucose between GG and GA genotype.Conclusions:1. The Incidence rate of nonalcoholic fatty liver disease is 13.90%, and incidence of men was 16.23%, women 12. 13%. The subjects with nonalcoholic steatohepatitis take up 1. 33% of subjects with nonalcoholic fatty liver disease. There were seven risk factors of nonalcoholic fatty liver disease, including abdomen wall fat thickness, triglyceride, fasting serum glucose, BMI, albumin, abdomen circumference, mean blood pressure. HDL was protective factor.2. There was a relationship between serum leptin and hyperlipdimia. Not only leptin was enhanced in fatty liver but maybe involved in the pathogensis of fatty liver. Leptin resistance may occur in NAFLD.3. The serum adiponectin enhanced in nonalcoholic fatty liver disease, whereas the resistin decreased. There was a positive relationship between resistin and obesity, a negative relationship between adiponectin and obesity. The adiponectin negative correlated with FBS, positive correlated with HDL. But resistin had not relationships with blood pressure, hyperlipemia and FBS.4. Leptin receptor LyslO9Arg polymorphism may be involved in the regulation of abdominal wall fat thickness. Whether leptin receptor LyslO9Arg polymorphism affected fatty liver disease is still unknown. Leptin receptor Arg223Gln polymorphism may not be involved in the pathogenesis of nonalcoholic fatty liver disease. |
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