检测视黄醇结合蛋白4在非酒精性脂肪性肝病中的意义

目的探讨非酒精性脂肪性肝病(NAFLD)患者血清视黄醇结合蛋白4(RBP4)的临床意义。方法选择NAFLD肝患者62例,正常对照60例,采用ELISA方法测定空腹血清RBP4,同时检测其血糖、血脂、肝功能及胰岛素水平,并计算胰岛素抵抗指数(HOMA-IR)。结果与正常对照组比较,NAFLD患者的空腹血糖(FBG)、总胆固醇(TC)、甘油三酯(TG)、低密度酯蛋白(LDL-C)、血清胰岛素(FINS)、HOMA-IR、ALT、AST和RBP4显著增高(P<0.01),而且NAFLD患者治疗后血清RBP4水平显著降低。相关分析显示,血清RBP4与FBG、TC、TG、FINS、HOMA-IR呈正相关。结论在NAFLD的发病过程中,RBP4可能参与其发病,在其早期诊断和评判肝脏损害程度中有一定的临床意义。     

Decreased hepatic RBP4 secretion is correlated with reduced hepatic glucose production but is not associated with insulin resistance in patients with liver cirrhosis

Objective  Patients with liver cirrhosis have a high incidence of insulin resistance and diabetes. This study was designed to determine circulating levels and hepatic production of retinol-binding protein 4 (RBP4) in relation to parameters of hepatic and systemic metabolism in patients with liver cirrhosis.
Design and method  Circulating RBP4 levels were measured in 19 patients with liver cirrhosis at different clinical stages of the disease and in 20 age-, sex- and body mass index (BMI)-matched controls. Hepatic production rates of RBP4 and glucose were assessed by measuring the arterial hepatic venous concentration difference together with hepatic blood flow. Insulin resistance was determined by the Quantitative Insulin Sensitivity Check Index (QUICKI) and the homeostasis model assessment of insulin resistance (HOMA-IR), energy expenditure by indirect calorimetry and body composition by bioelectrical impedance analysis (BIA).
Results  Compared with controls, RBP4 levels in cirrhosis were decreased (8·1 ± 1·8 vs. 22·6 ± 2·4 mg/l, P  < 0·001) due to decreased hepatic production ( P <  0·05). RBP4 correlated with hepatic protein synthesis capacity ( P <  0·01), but not with insulin resistance, energy expenditure, BMI or body fat mass. Plasma RBP4 correlated with hepatic glucose production ( P <  0·05).
Conclusions  These data demonstrate that RBP4 in cirrhosis (i) is decreased due to reduced hepatic production, (ii) is not associated with insulin resistance, and (iii) might have a beneficial role by decreasing hepatic glucose production and could thus also be regarded as a hepatokine.     

Expression of adiponectin and its receptors in livers of morbidly obese patients with non-alcoholic fatty liver disease

Background and Aim:  Obesity is one of the risk factors for non-alcoholic fatty liver disease (NAFLD) and a common disease that comprises simple steatosis and non-alcoholic steatohepatitis (NASH), and can eventually lead to liver cirrhosis. Adiponectin is an adipocyte-derived protein that has anti-obesity, antidiabetic and anti-inflammatory properties, and is considered to possess a hepatoprotective function. Its role in the development and progression of NAFLD in morbidly obese patients is unknown. In this study, we examined the expression levels of adiponectin and its receptors in liver biopsies of morbidly obese patients and then determined whether there was an association with the disease severity.
Methods:  Liver biopsies from 30 morbidly obese patients (18 NASH vs 12 steatosis) were analyzed. The needle core biopsies were subjected to routine histological examination and stained immunohistochemically for adiponectin, adiponectin receptor I (adipoRI) and receptor II (adipoRII).
Results:  The two groups were comparable with respect to body mass index, age and gender distribution. The expression of adiponectin decreased in liver biopsies with NASH as compared to those with simple steatosis (1.61 ± 0.70 vs 2.25 ± 0.75, P  = 0.028). Spearman's rank correlation coefficient analysis showed that the staining intensity of adiponectin negatively correlated with the grade of inflammation ( r  = −0.368, P  = 0.045) and stage of fibrosis ( r  = −0.380, P  = 0.038). There was no significant difference in expression of adipoRI and adipoRII between the two groups.
Conclusion:  These findings indicate that decreased liver adiponectin expression may play a role in the development and progression of NAFLD, from simple steatosis to NASH, in morbidly obese patients.     

2型糖尿病合并非酒精性脂肪性肝病患者血清视黄醇结合蛋白4水平变化及影响因素的研究

目的 研究T2DM合并非酒精性脂肪性肝病（NAFLD）患者血清视黄醇结合蛋白4（RBP4）水平变化.方法 选取单纯T2DM患者（T2DM） 32例,T2DM合并NAFLD者（T2DM＋NAFLD）31例及正常对照（NC）者34名,测定血清RBP4水平,并计算胰岛β细胞功能指数（HOMA-β）及葡萄糖处置指数（DI）.结果 与其他两组比较,T2DM＋ NAFLD组血清RBP4水平最高（P＜0.05或P＜0.01）,而DI最低（P均＜0.01）.且TG、WC、SBP、DI是RBP4的独立影响因素（P均＜0.05）.RBP4是T2DM合并NAFLD独立危险因素（OR=1.142,P=0.057）.结论 血清RBP4在T2DM＋NAFLD组最高,与胰岛β细胞功能密切相关.     

Increased serum liver X receptor ligand oxysterols in patients with non-alcoholic fatty liver disease

Background

This study is a post-hoc analysis of a subset of patients who participated in our multi-institutional case-control study that evaluated the effects of pitavastatin in patients with non-alcoholic fatty liver disease (NAFLD) with hypercholesterolemia.

Methods

Serum samples of fifteen patients with biopsy-proven NAFLD with dyslipidemia were investigated. Serum markers of lipid metabolism were quantified by liquid chromatography-mass spectrometry (LC–MS)/MS. These data were then compared with those of 36 sex- and age-matched healthy controls. In addition, changes in these markers produced by treatment with pitavastatin were evaluated.

Results

Serum non-cholesterol sterols, reflecting intestinal cholesterol absorption, were significantly lower in the NAFLD patients compared to the controls, and the cholesterol synthesis marker, the ratio of lathosterol to cholesterol, was not significantly different between the two groups. Serum proportions of liver X receptor α (LXRα) ligand oxysterols (ratios to cholesterol) were significantly elevated in the NAFLD patients compared to the controls. The sum of oxysterols relative to cholesterol and the homeostasis model assessment as an index of insulin resistance (HOMA-IR) were significantly correlated. The marker representing cholesterol synthesis was significantly suppressed by pitavastatin treatment, from 3?months after initiation of the treatment, and the suppression remained significant during the observation period. The markers representing cholesterol absorption were unchanged at 3?months, but had significantly increased at 12?months. Serum oxysterol levels relative to cholesterol maintained high values and did not change significantly during the 12-month period of treatment.

Conclusions:

We speculate that serum LXRα ligand oxysterol levels (relative to cholesterol) could be surrogate markers of insulin resistance, and that high oxysterol levels in the circulation may play an important role in the development of hepatic and peripheral insulin resistance followed by NAFLD.     

Serum retinol-binding protein 4 levels are elevated in non-alcoholic fatty liver disease

Objective Retinol‐binding protein 4 (RBP4) is a recently identified adipokine that is elevated in the serum in several insulin‐resistant states. We investigated the relationship between non‐alcoholic fatty liver disease (NAFLD) and serum RBP4 in nondiabetic adults. Methods One hundred and fifty‐nine nondiabetic, non‐alcoholic subjects (95 males and 64 females) participated in this study. Division of subjects into a NAFLD group (n = 73; 45 males and 28 females) or a normal group (n = 86; 50 males and 36 females) was based on the presence of fatty liver disease determined by sonography. Results Serum RBP4 levels in the NAFLD group were significantly higher than those in the normal group (62·8 ± 16·0 mg/l vs. 51·7 ± 14·6 mg/l, P < 0·0001). Multiple logistic regression analysis revealed that the RBP4 level was an independent factor associated with NAFLD (P = 0·0042). In addition, serum RBP4 levels were positively correlated with serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ‐glutamyltranspeptidase (GGT) levels. The significant association between serum RBP4 and GGT levels remained even after adjusting for age, gender, body mass index, the homeostasis model of assessment (HOMA) value and the presence of NAFLD (r = 0·3097, P = 0·0002). Conclusion Serum RBP4 levels are significantly associated with NAFLD and liver enzymes.     

Serum retinol binding protein 4 and nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus

Retinol binding protein 4 (RBP4) is a protein secreted by adipocytes, and closely associated with insulin resistance. Whereas RBP4 is also mainly expressed in hepatocytes as the principal transport protein for retinol (vitamin A) in the circulation, and its pathophysiological role in liver remain unclear. The aim of this paper was to investigate the association between RBP4 and nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM). Serum RBP4 and adiponectin concentrations were measured by radioimmunoassay in 52 diabetic patients who had NAFLD and 50 sex- and age-matched diabetic patients without any clinical features of liver diseases who had normal liver ultrasonic appearance and normal liver function. Serum RBP4 levels were elevated in diabetic patients with NAFLD (32.0+/-8.9 microg/ml vs. 41.3+/-9.8 microg/ml, p<0.001), while adiponectin decreased (17.4+/-9.3 microg/ml vs. 13.8+/-7.0 microg/ml, p=0.032). Male diabetic patients had higher serum RBP4 concentration and lower serum adiponectin concentration than female diabetic patients (38.5+/-9.9 microg/ml vs. 34.0+/-10.7 microg/ml, p=0.031 and 12.7+/-5.7 microg/ml vs. 20.23+/-9.8 microg/ml, p<0.001, respectively). Multiple logistic regression analysis revealed RBP4 and triglyceride as independent association factors for NAFLD, while the association between serum adiponectin and NAFLD was not significant. Increasing concentrations of RBP4 were independently and significantly associated with NAFLD in diabetic patients. In multiple linear regression analysis, alanine aminotransferase, fasting serum insulin and adiponectin were independent factors for serum RBP4 level. The study demonstrates that retinol binding protein 4 might contribute to the pathogenesis of nonalcoholic fatty liver disease.     

Elevation of serum aminotransferase activity increases risk of carotid atherosclerosis in patients with non-alcoholic fatty liver disease

Background and Aim:  Patients with non-alcoholic fatty liver disease (NAFLD) have an increased risk of atherosclerosis and alanine aminotransferase (ALT) is associated with insulin resistance independently of metabolic factors. The aim of the present study was to investigate whether NAFLD patients with ALT elevation had a higher risk of carotid atherosclerosis.
Methods:  A total of 190 individuals were enrolled from the health management center. Among them, 20 subjects were excluded due to the presence of hepatitis B surface antigen (HbsAg), anti-hepatitis C virus (HCV) and cardiovascular disease. NAFLD was diagnosed by ultrasound examination. Carotid ultrasonography was used to measure maximal intima-media thickness (IMT) of the common carotid artery (CCA) and IMT (mean) > 1.0 mm was defined as the presence of carotid atherosclerosis.
Results:  NAFLD patients with ALT elevation had increased risk of carotid atherosclerosis than those with normal ALT by Fisher's exact test ( P  < 0.05). Multivariate analyses showed that serum ALT levels were positively associated with carotid atherosclerosis after adjustment for age, sex, number of metabolic syndrome components or status of metabolic syndrome (OR, 1.44; 95% CI 1.09–1.89; OR, 1.45; 95% CI 1.11–1.91). In addition, the higher the serum ALT levels with every 10 IU/L increment, the greater the risk of carotid atherosclerosis.
Conclusions:  Serum ALT levels are positively associated with the risk of carotid atherosclerosis in patients with NAFLD, suggesting that serum ALT levels could serve as a surrogate marker of cardiovascular risk in this special clinical setting.     

Protein glutathionylation increases in the liver of patients with non-alcoholic fatty liver disease

Background and Aim:  Oxidative stress is an important pathophysiological mechanism in non-alcoholic steatohepatitis, where hepatocyte apoptosis is significantly increased correlating with disease severity. Protein glutathionylation occurs as a response to oxidative stress, where an increased concentration of oxidized glutathione modifies post-translational proteins by thiol disulfide exchange. In this study, we analyzed the protein glutathionylation in non-alcoholic fatty liver disease (NAFLD) and evaluated a potential association between glutathionylation, fibrosis, and vitamin E treatment.
Methods:  Protein glutathionylation was studied in the livers of 36 children (mean age 12.5 years, range 4–16 years) subdivided into three groups according to their NAFLD activity score (NAS) by Western blot analysis and immunohistochemistry, using a specific monoclonal antibody. In addition, we identified the hepatocyte ultrastructures involved in glutathionylation by immunogold electron microscopy.
Results:  Our findings showed that protein glutathionylation increases in the livers of patients with NAFLD and it is correlated with steatohepatitis and liver fibrosis. Its increase appears mainly in nuclei and cytosol of hepatocytes, and it is reversed by antioxidant therapy with reduced fibrosis.
Conclusion:  Protein glutathionylation significantly increases in livers with NAFLD, strongly suggesting that oxidative injury plays a crucial role in this disease. Furthermore, the marked increase of protein glutathionylation, in correlation with collagen VI immunoreactivity, suggests a link between the redox status of hepatic protein thiols and fibrosis.     

Circulating retinol-binding protein 4 is associated with the development and regression of non-alcoholic fatty liver disease

AimRetinol-binding protein 4 (RBP4), primarily secreted by liver and adipose tissue, has been linked with non-alcoholic fatty liver disease (NAFLD). However, investigations on the relationships between RBP4 and NAFLD have produced inconsistent results. Therefore, the association between serum RBP4 levels and the development or regression of NAFLD was prospectively investigated.MethodsA total of 3389 Chinese adults, aged 40–75 years and followed-up for 3.09 years, were included and analyzed in the study. NAFLD was diagnosed by abdominal ultrasonography. Serum RBP4 levels were measured, and their relationship to NAFLD development and regression assessed.ResultsOf the 1318 participants without NAFLD at baseline, 410 developed NAFLD after follow-up. Baseline RBP4 was positively associated with incident NAFLD: the fully adjusted odds ratio (OR) was 2.01 with a 95% confidence interval (CI) of 1.33–3.04 (P = 0.003 for trend). After follow-up, a significant increase in RBP4 levels was observed in participants who developed NAFLD. On the other hand, in 1382 subjects diagnosed with NAFLD at baseline, 339 experienced NAFLD regression after follow-up. Thus, baseline RBP4 was inversely associated with NAFLD regression: the fully adjusted OR was 0.52 with a 95% CI of 0.34–0.80 (P < 0.001 for trend). A significant decrease in RBP4 after follow-up was also noted in participants with NAFLD regression.ConclusionSerum RBP4 concentrations are associated with the development and regression of NAFLD, making them a potential novel preventative and therapeutic target in NAFLD management.     

Serum neopterin levels in patients with non-alcoholic steatohepatitis

Aim:  Neopterin is a marker of cell-mediated immunity. It also has a fundamental role in host-defense reactions, including interactions with reactive oxygen intermediates and the promotion of local and systemic oxidative stress. The present study aimed to assess the importance of serum neopterin levels in patients with non-alcoholic steatohepatitis (NASH).
Methods:  Thirty-nine patients with NASH diagnosed by liver biopsy and 32 healthy adults (controls) were enrolled in the study. Serum neopterin levels were measured with an enzyme-linked immunosorbent assay in addition to other biochemical parameters, including liver enzymes. Histopathological examinations were graded as suggested by both the necroinflammatory activity grading system and the NASH scoring system.
Results:  The mean serum neopterin levels were higher in patients with NASH compared to the controls (24.1 ± 16.4 vs 16.2 ± 9.5, P  = 0.019). The histological examination of liver biopsies revealed that 34 of the patients with NASH had grade 1 steatohepatitis and only five patients had grade 2 steatohepatitis. A higher serum mean neopterin level was detected in grade 2 patients compared to grade 1 (40.6 ± 5.6 vs 21.7 ± 16.1, P  = 0.014). A gradual increase was also observed in serum neopterin levels with the increase of the NASH score.
Conclusion:  The serum neopterin levels were significantly higher in patients with NASH compared to the controls, and levels showed an association with the severity of liver damage.     

Circulating microRNAs in patients with non-alcoholic fatty liver disease

AIM: To identify novel non-invasive biomarkers for non-alcoholic fatty liver disease(NAFLD). METHODS: Twenty patients with histologically proven NAFLD and 20 controls were included. All NAFLD cases were scored using the NAFLD activity score. The rela-tive expressions of miR-197, miR-146 b, miR-10 b, miR-181d, miR-34 a, miR-122, miR-99 a and miR-29 a were analyzed using real-time polymerase chain reaction. RESULTS: Serum levels of miR-181 d, miR-99 a, miR-197 and miR-146 b were significantly lower in biopsy-proven NAFLD patients than in the healthy controls. Serum lev-els of miR-197 and miR-10 b were inversely correlated with degree of inflammation and miR-181 d and miR-99 a were inversely correlated with serum gamma glu-tamyl transferase levels in non-alcoholic steatohepatitis patients. CONCLUSION: NAFLD is associated with altered se-rum miRNA expression pattern. This study provides clues for defining the non-invasive diagnosis of NAFLD.     

Polymorphism of human leptin receptor gene is associated with type 2 diabetic patients complicated with non-alcoholic fatty liver disease in China

Background and Aim:  To investigate the relationship between human leptin receptor ( LEPR ) gene G3057A polymorphism and type 2 diabetes mellitus (T2DM) patients complicated with or without non-alcoholic fatty liver disease (NAFLD).
Methods:  Two hundred and sixteen cases of newly diagnosed T2DM patients (104 cases complicated with NAFLD) and 108 cases of normal glucose tolerances (NGT) were recruited. Hemi-nested polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and PCR-direct sequence analysis were conducted to detect the polymorphism of LEPR G3057A variation. Plasma leptin levels were measured by enzyme-linked immunosorbent assay kit. Plasma lipid and glucose metabolic parameters were measured routinely. Liver ultrasound was carried out for all subjects.
Results:  T2DM patients complicated with NAFLD had higher plasma insulin, leptin, triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) levels than those without NAFLD and NGT subjects. The variant frequency at nucleotide 3057 G→A transversion was 76.0% in type 2 diabetic patients complicated with NAFLD, which was also significantly higher than those without NAFLD (62.1%) and NGT cases (53.2%). There was also significant difference in genotype distribution between the three groups (χ² = 14.63, P  < 0.01).
Conclusion:  The polymorphism of LEPR gene 3057 probably contributes to the onset of NAFLD by regulating lipid metabolism and affecting insulin sensitivity.     

非酒精性脂肪性肝病合并2型糖尿病患者血清抵抗素和黄醇结合蛋白4水平及其临床意义探讨

目的 探讨非酒精性脂肪性肝病(NAFLD)合并2型糖尿病(T2DM)血清抵抗素和黄醇结合蛋白4(RBP4)水平变化及其临床意义。方法 2017年10月～2021年1月我院诊治的NAFLD合并T2DM患者106例和NAFLD患者106例,检测空腹血糖(FBG),采用化学发光法检测空腹胰岛素(FINS)水平,计算HOMA-β指数和胰岛素抵抗指数(HOMA-IR),采用ELISA法检测血清抵抗素、RBP4、肿瘤坏死因子(TNF-α)和白介素(IL-6)水平。结果 合并T2DM患者血清TC和HDL-C水平分别为(4.7±0.5)mmol/L和(1.1±0.2)mmol/L,显著低于NAFLD患者【分别为(5.6±0.6)mmol/L和(1.4±0.3)mmol/L,P<0.05】;合并T2DM患者血清GGT水平(102.3±15.5)U/L,显著高于NAFLD患者【(71.6±4.6),P<0.05】,而两组血清ALT、AST和ALP水平无显著性差异(P>0.05);合并T2DM患者血清FBG、FINS和HOMA-IR水平分别为(7.7±0.8)mmol/L、(6.7±1.2...     

Influence of inducible nitric oxide synthase polymorphisms in Japanese patients with non-alcoholic fatty liver disease

Aim:  Genetic factors as well as environmental factors play an important role in the development of non-alcoholic fatty liver disease (NAFLD). Recently, inducible nitric oxide synthase (iNOS) was significantly higher in the severest form of non-alcoholic steatohepatitis (NASH), and nitric oxide (NO) has been determined to play an important role in the process of fibrosis in NASH. In this study, we investigated iNOS gene polymorphisms for associations with NAFLD.
Methods:  A total of 115 NAFLD patients, consisting of 65 patients with NASH and 50 patients with simple steatosis, in whom a positive diagnosis had been made by liver biopsy, and 435 healthy control subjects, were recruited into this study.
Results:  We investigated 10 single nucleotide polymorphisms (SNP) of the iNOS gene, one of which, rs1060822, had the lowest P -value in the allele frequency model ( P  = 0.00078) with an odds ratio (95% confidence interval) of 0.49 (0.32–0.75). Four SNP, rs2297510, rs2297511, rs2797512 and rs1060822, were significantly associated with NAFLD, even when the most conservative Bonferroni's correction was applied. Linkage disequilibrium analysis revealed that SNP rs1060822 and three other SNP, rs2297510, rs2297511 and rs2797512, were in the same block. We also investigated associations between rs1060822 genotypes and the fibrosis index, and the results of the analysis revealed an additive increase in the fibrosis index and intrahepatic iNOS mRNA expression in the patients with the T allele of rs1060822.
Conclusion:  This is the first study to identify genetic variations in iNOS that may influence the risk of NAFLD and liver fibrosis in NAFLD.     

Serum levels of hepatoprotective peptide adiponectin in non-alcoholic fatty liver disease

OBJECTIVE: Adiponectin is an adipose tissue-specific protein that has anti-inflammatory, antidiabetic and antiobesity effects. It has been suggested that adiponectin has a hepatoprotective role. Non-alcoholic fatty liver disease (NAFLD) is becoming more prevalent with increasingly adverse clinical outcomes. In this study, serum adiponectin levels were investigated in patients with NAFLD to determine its possible role on hepatic inflammation and injury. METHODS: Twenty-nine biopsy-proven NAFLD patients (14 women, 15 men) with elevated liver enzymes, 20 clinically diagnosed NAFLD patients (13 women, seven men) with normal liver enzymes, and 20 healthy adults (10 women, 10 men) were enrolled. From fasting blood samples, serum adiponectin levels were measured by enzyme-linked immunosorbent assay. The body mass index, serum glucose, insulin, cholesterol and triglyceride levels were determined. RESULTS: Serum adiponectin levels were 4.99+/-2.1, 9.49+/-3.91 and 7.74+/-4.41 micro/ml in the NAFLD with elevated liver enzymes, NAFLD with normal liver enzymes and healthy adult control groups, respectively. The mean serum adiponectin level in the NAFLD with elevated liver enzymes group was significantly lower than those of other groups tested (P<0.001). Insulin, cholesterol and triglyceride levels of NAFLD patients with elevated liver enzymes were significantly higher than control groups (P<0.05) but were not significantly different from the NAFLD group with normal liver enzymes (P>0.05). On histopathologic examination, the mean serum adiponectin levels of non-alcoholic steatohepatitis patients with grade 2 or more inflammatory activity was significantly lower than patients with grade 1 inflammatory activity (P=0.013). CONCLUSION: Serum adiponectin levels are significantly lower in NAFLD patients with elevated liver enzymes. Non-alcoholic steatohepatitis patients show lower levels of adiponectin with higher grades of inflammation.     

Plasma adiponectin is decreased in nonalcoholic fatty liver disease

OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver-related morbidity and is frequently associated with obesity and metabolic syndrome. The recently discovered hormone adiponectin is produced by adipose tissue, and low plasma adiponectin is considered a key factor in the development of the insulin resistance underlying metabolic syndrome. Animal studies suggest that adiponectin may protect against non-alcoholic steatohepatitis, but direct evidence in humans is lacking. We therefore conducted this study to assess the relationship between plasma adiponectin and nonalcoholic fatty liver disease to explore its role in the pathogenesis of this disease. DESIGN AND METHODS: We measured plasma adiponectin and anthropometric, biochemical, hormonal and metabolic correlates in a group of 17 NAFLD patients with diagnosis confirmed by biopsy, and 20 controls with comparable age, body-mass index and sex. Furthermore we compared plasma adiponectin in patients with simple steatosis and steatohepatitis. RESULTS: Plasma adiponectin was significantly lower in NAFLD patients than controls (5.93+/-0.45 vs 15.67+/-1.60ng/ml). Moreover, NAFLD patients were significantly more insulin resistant while having similar serum leptin. Adiponectin was similar in simple steatosis and in steatohepatitis (6.16+/-0.78 vs 5.69+/-0.49ng/ml). An inverse correlation was observed between adiponectin and homeostatic model assessment (HOMA) of insulin resistance (P = 0.008), while adiponectin did not correlate with serum transaminases and lipid values. CONCLUSIONS: These data support a role for low circulating adiponectin in the pathogenesis of NAFLD and confirm the strict association between reduced adiponectin production by adipose tissue, NAFLD and insulin resistance.     

非酒精性脂肪肝血尿酸水平与胰岛素抵抗的相关性

目的:研究非酒精性脂肪肝(non-alcoholic fatty liver,NAFL)患者血尿酸水平及其与胰岛素抵抗程度的相关性.方法:选取单纯NAFL患者40例,NAFL合并2型糖尿病患者(type2diabetes mellitus,T2DM)72例,健康体检者62名为研究对象.测定体重指数(body mass index,BMI),检测空腹血糖(fasting blood glucose,FBG)、尿酸(serum uric acid,SUA)、丙氨酸氨基转移酶(alanine aminotransferase,ALT)、门冬氨酸氨基转移酶(aspartate aminotransferase,AST)、胆固醇(cholesterol,TC)、甘油三酯(triglyceride,TG)、糖化血红蛋白(glycated hemoglobin,HbA1C)、尿微量白蛋白/尿肌酐(Ualb/UCr)等生化指标并行肝脏B超检查.放射免疫法测定空腹胰岛素(fasting insulin,FINS),计算胰岛素抵抗指数(HOMA IR).结果:NAFL合并T2DM组BMI、SUA、ALT、AST、TG、FBG、FINS、HOMA IR、HbA1C、Ualb/UCr、SF均高于对照组;与单纯NAFL比较,NAFL合并T2DM组胰岛素抵抗及SUA水平更重;相关性研究表明FBG、HOMA IR、HbA1C与SUA呈正相关.结论:NAFL患者存在明显的胰岛素抵抗及高血尿酸血症,且两者具有一定的相关性.降低胰岛素抵抗联合纠正尿酸代谢紊乱对防止NAFL的发生发展具有重要的临床意义.     

RBP-to-retinol ratio, but not total RBP, is elevated in patients with type 2 diabetes

Aim:  It was recently reported that serum retinol-binding protein (RBP), also known as retinol-binding protein 4 (RBP4), was positively associated with systemic insulin resistance. We hypothesized that an imbalance between RBP and retinol might be the underlying cause for this association.
Methods:  We studied the ratio between RBP and retinol in 233 humans divided into groups depending on normal glucose tolerance (NGT), impaired glucose tolerance (IGT), type 2 diabetes (T2DM) and presence or absence of obesity.
Results:  Plasma RBP and retinol levels were lower in patients with T2DM than in individuals with NGT (p < 0.05 and p < 0.0001 respectively). In contrast, RBP-to-retinol ratio was higher in individuals with T2DM (p < 0.0001) and IGT (p < 0.05). Following multivariate adjustment, RBP and retinol correlated positively with low-density lipoprotein (LDL) and triglycerides (p < 0.0001, except retinol and LDL: p < 0.001). RBP-to-retinol ratio correlated positively with glucose 2 h after an oral glucose tolerance test (p < 0.0001) and with C-reactive protein (p < 0.001). Retinol, RBP and adipose tissue RBP messenger RNA (mRNA) levels shared an inverse relationship with plasma interleukin-6, and adipose tissue RBP mRNA levels correlated positively with plasma tumour necrosis factor-α (TNF-α) and skeletal muscle TNF-α mRNA levels.
Conclusions:  Our results suggest that the excess of RBP relative to retinol, assessed as the RBP-to-retinol ratio, is more indicative of T2DM than RBP itself. Hence, the previously reported insulin resistance in mice induced by overexpression or injection of RBP could be because of higher levels of RBP relative to retinol rather than higher total levels of RBP. Moreover, TNF-α may have a role in RBP-mediated adipose to muscle crosstalk.     

Association between low thigh fat and non-alcoholic fatty liver disease

Background and Aim:  Some people have a fatty liver despite having low visceral fat and a low body mass index (BMI). We investigated whether fat distribution, especially thigh subcutaneous fat and thigh intramuscular fat, is associated with non-alcoholic fatty liver disease (NAFLD).
Methods:  The patients consisted of 408 men and women. NAFLD was defined by an ultrasound scan and excluded other liver diseases. Visceral, subcutaneous abdominal, intramuscular, and subcutaneous thigh adipose tissue was measured by computed tomography.
Results:  The frequency of NAFLD decreased over a quartile of thigh fat independently of BMI in the female patients. Additional adjustments for age and visceral fat area did not change the results. This finding was not observed in the male patients. To investigate the relationship between each fat distribution and NAFLD, we performed a logistic regression analysis. Fat distribution was divided into four groups: visceral fat, abdominal subcutaneous fat, thigh subcutaneous fat, and thigh intramuscular fat. All four fat components were chosen as variables for the regression model. Age, BMI, and the homeostasis model assessment (HOMA) index were then adjusted successively. A larger subcutaneous fat area was negatively associated with NAFLD after adjustment for visceral fat and abdominal subcutaneous fat areas in women, but not in men. It did not change even after age adjustment, BMI, and the HOMA index.
Conclusion:  Low femoral subcutaneous fat amounts were shown to be independently associated with fatty liver disease in women. These results show the importance of accurate measurements of other regional body compositions as well as visceral fat amounts when investigating NAFLD.