Serum alanine aminotransferase is associated with serum adiponectin, C-reactive protein and apolipoprotein B in young healthy men.

Several studies have reported an association between markers of liver injury, including elevated concentrations of alanine aminotransferase (ALT) aspartate aminotransferase (AST), and prospective risk of type 2 diabetes. We therefore examined the relationship between ALT and AST on the one hand, and serum adiponectin and highly sensitive CRP on the other, both of which have been reported to be associated with prospective risk of type 2 diabetes; we also tested for variable components of metabolic syndrome in 198 male college students aged 18-20 years. ALT showed a positive relationship with percentage body fat (r = 0.19, p = 0.02), serum leptin (r = 0.21, p = 0.01), LDL cholesterol (r = 0.29, p = 0.0003), triglyceride (r = 0.28, p = 0.0004) and apolipoprotein B (r = 0.35, p < 0.0001) even after adjustment for body mass index (BMI). Although there was a significant relationship with serum insulin, adiponectin (inversely), homeostasis model assessment of insulin resistance, systolic and diastolic blood pressure, HDL cholesterol (inversely) and LDL particle diameter in simple regression analysis, significance disappeared after adjustment for BMI. In contrast, CRP (r = 0.16, p = 0.04) was associated with ALT after adjustment for BMI, although simple regression analysis revealed no association between the two. Relationships were smaller for AST, and significance disappeared after adjustment for BMI. Multiple regression analysis excluding lipid variables revealed significant and independent associations of ALT with adiponectin and percentage body fat. In a model including lipid variables, apolipoprotein B emerged as an independent predictor of ALT in addition to adiponectin and percentage body fat. These variables explained 29 % of ALT variability. In conclusion, serum ALT levels were associated with leptin and CRP as well as many components of the insulin resistance syndrome in young healthy men. Adiponectin, apolipoprotein B and percentage body fat emerged as significant and independent predictors of ALT. Since adiponectin and chronic subclinical inflammation have been reported to predict the development of type 2 diabetes and since abnormalities in apolipoprotein B metabolism occur in the early course of insulin resistance, these findings may be compatible with the association between liver markers and risk of diabetes.     

Clinical relevance of lipid panel and aminotransferases in the context of hepatic steatosis and fibrosis as measured by transient elastography (FibroScan®)

BackgroundNonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease and is associated with various co-morbidities. Transient elastography (FibroScan®) is a non-invasive method to detect NAFLD using the controlled attenuation parameter (CAP). We aimed to evaluate the association of the lipid panel and aminotransferases concentrations with the presence or absence of steatosis and fibrosis.MethodsOne hundred and five patients with NAFLD were included. Hepatic steatosis was quantified by CAP (dB/m) and liver stiffness by Kilopascals (kPa), these values were then analyzed against patient lipid panel and serum concentrations of the liver enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT). A correlation and multiple regression were used. Mann-Whitney U test was used as non-parametric analysis.ResultsWe observed an association between hepatic steatosis and total cholesterol (B = 0.021, p = 0.038, Exp (B) = 1.021, I.C = 1.001-1.041) as well as serum triglycerides (B = 0.017, p = 0.006, Exp (B) = 1.018 and I.C = 1.005-1.030). Similarly, we found an association between significant hepatic fibrosis and lower concentrations of total cholesterol (B = -0.019, p = 0.005, Exp (B) = 0.982 I.C = 0.969-0.995) and elevated AST (B = 0.042, p = 3.25 × 10^-4, Exp (B) = 1.043 I.C = 1.019-1.068) independent of age, gender and BMI.ConclusionsOur results suggest that, total cholesterol and triglyceride concentrations positively correlate with hepatic steatosis while significant hepatic fibrosis is associated with lower total cholesterol and higher AST concentrations.     

Tumor necrosis factor alpha system and plasma adiponectin concentration in women with gestational diabetes.

Plasma concentrations of adiponectin, tumor necrosis factor-alpha (TNF-alpha) and its soluble receptors sTNFR-1 and sTNFR-2 were measured in 80 patients with gestational diabetes (GDM) (mean age 29.0 +/- 4.9 years) and 30 pregnant women with normal glucose tolerance (NGT) (mean age 28.2 +/- 6.0 years). We found that GDM patients had significantly lower concentrations of adiponectin (11.28 +/- 5.91 vs. 16.31 +/- 6.04 microg/ml, p = 0.00009) and elevated levels of TNF-alpha (1.71 +/- 0.92 vs. 1.27 +/- 0.42 pg/ml, p = 0.0175) in comparison to NGT women. The differences remained statistically significant after adjusting for BMI. Plasma levels of sTNFR-1 and sTNFR-2 also tended to be higher in GDM patients. In the GDM group TNF-alpha concentrations correlated significantly with sTNFR-1 (r = 0.444, p = 0.00008), sTNFR-2 (r = 0.364, p = 0.0016) and with C-peptide concentrations (r = 0.318, p = 0.016), whereas in women with NGT TNF-alpha correlated only with TG levels (r = 0.50, p = 0.024). Multivariate linear regression analysis revealed that prepregnant BMI was the most predictive indicator of TNF-alpha concentrations in GDM women. TG concentrations as well as BMI before pregnancy and at the time of sampling in pregnant NGT women were significant predictors, explaining 62% of the variance in TNF-alpha concentration. There were also negative correlations between adiponectin concentrations and a pregestational BMI (r = - 0.298, p = 0.009), BMI at the time of sampling (r = - 0.239, p = 0.034) and TG concentrations (r = - 0.379, p = 0.039) in GDM patients, whereas women with NGT showed only a negative correlation between adiponectin and TG concentrations (r = - 0.488, p = 0.025). In a multivariate regression analysis, prepregnancy BMI and TG levels remained significant predictors, explaining 39% of the variation in plasma adiponectin concentration in GDM women. In conclusion, our results suggest that decreased adiponectin concentration in GDM may not simply reflect maternal adiposity and insulin resistant state, but may contribute to the impaired glucose metabolism during pregnancy, with potential implications for screening and prevention of the disease.     

Elevated serum GGT concentrations predict reduced insulin sensitivity and increased intrahepatic lipids.

Elevated serum gamma-glutamyltransferase (GGT) concentrations have been related to features of the metabolic syndrome as well as increased risk of cardiovascular and liver disease. More recently, elevated GGT levels were shown to predict development of type 2 diabetes in a longitudinal study from Korea. The aim of the present study was to test the hypothesis that serum GGT is associated with glucose tolerance, insulin sensitivity and beta-cell function in a healthy, non-diabetic Caucasian population from the Tübingen family study. Insulin sensitivity was estimated by oGTT (n = 850) or measured by hyperinsulinemic euglycemic clamp (n = 245), respectively. A subgroup (n = 70) underwent additional determination of intrahepatic lipid content using 1H magnetic resonance spectroscopy. Serum GGT was positively correlated with two-hour glucose during oGTT (r = 0.15, p < 0.0001) and negatively correlated with insulin sensitivity from oGTT (r = -0.31, p < 0.0001) and clamp (r = -0.27, p < 0.0001). The relationship between GGT and insulin sensitivity remained significant after adjusting for sex, age, BMI, and AST using multivariate regression analysis. Inclusion of serum triglyceride levels as a parameter of lipid metabolism kept the relationship significant in the oGTT group (p < 0.0001), but not in the smaller clamp group (p = 0.11). Additionally, serum GGT was positively correlated with hepatic lipid content (r = 0.49, p < 0.001) independent of sex, age, BMI, AST or serum triglycerides. There was no significant correlation between GGT and the index for beta-cell function after adjusting for age, sex, BMI and insulin sensitivity (p = 0.74). In conclusion, elevated serum GGT levels predict glucose intolerance probably via insulin resistance rather than beta-cell dysfunction. This may be primarily related to hepatic insulin resistance and increased intrahepatic lipids. The association observed between elevated hepatic lipids and reduced insulin sensitivity might explain the increased diabetes risk observed in subjects with elevated serum GGT concentrations. In the absence of overt liver disease, elevated serum GGT concentrations may point the clinician to incipient disturbances in the glucose metabolism.     

Immune responses against oxidative stress-derived antigens are associated with increased circulating tumor necrosis factor-alpha in heavy drinkers

Growing evidence indicates that pro-inflammatory cytokines play a key role in alcoholic liver disease (ALD). This study investigates whether immune response toward oxidative stress-derived antigens could be involved in promoting cytokine production in alcohol abusers. Cytokine profile and circulating IgG against human serum albumin modified by malondialdehyde (MDA-HSA) and against oxidized cardiolipin (Ox-CL) were evaluated in 59 heavy drinkers (HD) with (n=30) or without (n=29) ALD and 34 healthy controls. IgG against MDA-HSA and Ox-CL were significantly higher in HD with ALD than in HD without liver injury or healthy controls. The elevation of these antibodies was associated with higher circulating levels of IL-2 (p=0.005) and TNF-alpha (p=0.001), but not of IL-6 or IL-8. The prevalence of abnormal TNF-alpha was 5-fold higher in HD with oxidative stress-induced IgG than in those without. HD with the combined elevation of both TNF-alpha and oxidative stress-induced IgG had 11-fold (OR 10.7; 95%CI 1.2-97.2; p=0.023) greater risk of advanced ALD than those with high TNF-alpha, but no immune responses. Moreover, the combined elevation of TNF-alpha and lipid peroxidation-derived IgG was an independent predictor of ALD in HD. We propose that immune responses towards oxidative stress-derived antigen promote TNF-alpha production and contribute to liver damage in alcohol abusers.     

Circulating soluble CD36 is a novel marker of liver injury in subjects with altered glucose tolerance

Liver injury linked to insulin resistance is characterized by mild to moderate increases in aminotransferase activity. A soluble form of CD36 (sCD36) was recently identified in human plasma. The aim of this study was to evaluate the relationships among plasma sCD36, insulin sensitivity (SI) and indicators of liver health. We evaluated a cohort of men from the general population (n=117). As expected, serum (ALT), aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT) were associated positively with body mass index (BMI) and age and negatively with SI (minimal model method). Circulating sCD36 was positively associated with ALT, AST and GGT in subjects with altered glucose tolerance, but not in those with normal glucose tolerance. The difference in the slope of the relationships was significant (P=.01). Age, BMI and triglycerides (but not sCD36) contributed independently to 29% of ALT variance in subjects with normal glucose tolerance. In contrast, SI and sCD36 contributed independently to 39% of ALT variance in subjects with altered glucose tolerance. The correlation between ALT activity and sCD36 was confirmed in an independent, replication study. In summary, circulating sCD36 could represent a novel marker of liver injury in subjects with altered glucose tolerance.     

血清IL-1RA水平与非酒精性脂肪性肝病的相关性及无创诊断的临床价值

目的:探究血清白介素-1受体拮抗剂(IL-1RA)与非酒精性脂肪性肝病(NAFLD)进展的相关性,以及无创性预测诊断NASH的临床价值。方法:选取确诊NAFLD病例60例,配套肝穿刺活检组织标本及肝穿前一周血清。经B超检查无脂肪肝症状的正常健康人群30例,作为对照。测量身高、体重、腰围等生理指标,计算BMI;检测ALT、AST、AST/ALT、ALP、GGT、TC、TG、HDL、LDL等生化指标;双抗夹心法测定血清中IL-1RA浓度水平。结果:血清IL-1RA与ALT、AST及GGT具有相关性(P0.05),与肝细胞脂肪变性、气球样变、小叶内炎症、汇管区炎症及纤维化程度呈高度相关(P0.01);随NAS评分增高其浓度增大,呈高度正相关(r=0.915,P0.01);NASH患者血清中IL-1RA明显高于Non-NASH患者(t=2.88,P0.01),经ROC曲线分析,曲线下面积AUROC=0.986,利用Youden指数确定最佳敏感性为89.7%,特异性为97.9%,最佳cut-off值为171.8 ng/L。结论:NASH患者血清IL-1RA水平明显升高,血清IL-1RA可作为评价NASH及其严重程度的独立预测因子,可以作为一个无创性诊断指标对NASH进行诊断。     

Alcohol consumption and dietary patterns: the FinDrink study

The aim of this population-based study was to investigate differences in dietary patterns in relation to the level of alcohol consumption among Finnish adults. This study was part of the FinDrink project, an epidemiologic study on alcohol use among Finnish population. It utilized data from the Kuopio Ischaemic Heart Disease Risk Factor Study. A total of 1720 subjects comprising of 816 men and 904 women aged 53-73 years were included in the study in 1998-2001. Food intake was collected via a 4-day food diary method. Self-reported alcohol consumption was assessed with quantity-frequency method based on the Nordic Alcohol Consumption Inventory. Weekly alcohol consumption was categorized into three groups: non-drinkers (<12 grams), moderate drinkers (12-167.9 grams for men, 12-83.9 grams for women) and heavy drinkers (≥ 168 grams for men, ≥ 84 grams for women). Data were analyzed for men and women separately using multiple linear regression models, adjusted for age, occupational status, marital status, smoking, body mass index and leisure time physical activity. In women, moderate/heavy drinkers had lower fibre intake and moderate drinkers had higher vitamin D intake than non-drinkers. Male heavy drinkers had lower fibre, retinol, calcium and iron intake, and moderate/heavy drinkers had higher vitamin D intake than non-drinkers. Fish intake was higher among women moderate drinkers and men moderate/heavy drinkers than non-drinkers. In men, moderate drinkers had lower fruit intake and heavy drinkers had lower milk intake than non-drinkers. Moderate drinkers had higher energy intake from total fats and monosaturated fatty acids than non-drinkers. In contrast, energy intake from carbohydrates was lower among moderate/heavy drinkers than non-drinkers. In conclusion, especially male heavy drinkers had less favorable nutritional intake than moderate and non-drinkers. Further studies on the relationship between alcohol consumption and dietary habits are needed to plan a comprehensive dietary intervention programs in future.     

Effects of β‐carotene on antioxidant status in rats with chronic alcohol consumption

This study examined the effects of β‐carotene on antioxidant status in rats with chronic alcohol consumption. At the beginning of experiment (week 0), according to both the plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, rats (n = 24) were divided into 3 groups and fed with a standard diet (group C), a diet containing ethanol (group E), or a diet containing ethanol and β‐carotene (group E+B). After 10 weeks, plasma AST and ALT, fat accumulation in the liver, antioxidant enzyme activities in erythrocytes and the liver, malondialdehyde (MDA), and α‐tocopherol and retinol in plasma and hepatic samples were analyzed. The chronic alcohol diet significantly increased AST and ALT levels in plasma, and these changes were prevented by supplementing the diet with β‐carotene. Glutathione (GSH) in erythrocytes and in the liver was significantly elevated in rats fed with a diet containing β‐carotene. The results indicate that β‐carotene supplementation can prevent ethanol‐induced liver damage and increase GSH concentrations in erythrocytes and the liver. Copyright © 2009 John Wiley & Sons, Ltd.     

2 型糖尿病伴脂肪肝患者血浆FGF21水平与肥胖、脂代谢及胰岛素抵抗的相关性

目的:研究2型糖尿病伴脂肪肝患者血浆成纤维细胞生长因子21(FGF21)水平与肥胖、脂代谢及胰岛素抵抗的相关性,为临床诊疗提供依据。方法:选取2013年5月到2015年11月我院收治的2型糖尿病伴脂肪肝患者100例为研究组,另选取同期单纯脂肪肝患者100例为脂肪肝组,健康体检者100例为对照组,比较各组入选次日清晨FGF21、谷丙转氨酶(ALT)、谷草转氨酶(AST)、胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、游离脂肪酸(FFA)、体重指数(BMI)、腰臀比(WHR)、空腹胰岛素(FINS)、空腹血糖(FBG)以及胰岛素抵抗指数(HOMA-IR)。结果:研究组TG、TC、AST、ALT、LDL-C、FFA、FBG、BMI、WHR、FINS、HOMA-IR以及FGF21均显著高于对照组,HDL-C显著低于对照组,比较差异具有统计学意义(P0.05);研究组FFA、TG、FINS、FBG、HOMA-IR以及FGF21显著高于脂肪肝组,BMI和WHR显著低于脂肪肝组,比较差异具有统计学意义(P0.05);相关性分析显示:FGF21与TG、FFA、BMI以及HOMA-IR呈正相关关系(P0.05)。结论:2型糖尿病合并脂肪肝患者FGF21水平会显著升高,且与脂肪代谢、肥胖以及胰岛素抵抗有关。     

Potential Role of Interleukin‐18 in Liver Disease Associated with Insulin Resistance

Objective: Interleukin (IL)‐18 has been associated with obesity and insulin resistance, both risk factors for the development of liver disease, but the role of IL‐18 in liver disease associated with insulin resistance is presently unknown. We hypothesized that circulating IL‐18 would be related to serum concentrations of liver chemistry tests (LCTs) in apparently healthy subjects and wished to study whether this correlation was dependent on insulin sensitivity (S_I). Research Methods and Procedures: One hundred six apparently healthy white men consecutively enrolled in a cross‐sectional, population‐based study dealing with S_I in men were studied, and S_I (minimal model analysis), LCTs (colorimetry), and IL‐18 serum concentrations (immunoassay) were assessed. Results: Compared with subjects in the lowest quartile for serum IL‐18, subjects in the highest quartile exhibited increased serum triglycerides and decreased S_I, in addition to higher serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (all p < 0.05). The direct association between both ALT and AST and IL‐18 was further confirmed by examining the distribution of serum IL‐18 by quartiles of ALT and AST. Subjects in the highest quartile for serum ALT and AST had higher IL‐18 concentrations compared with subjects in the lowest quartile for these LCTs (both p = 0.01). In multiple regression analysis, IL‐18, but not S_I, was an independent predictor of serum concentrations of ALT and AST, explaining 7% and 4% of their variance, respectively. Discussion: In summary, IL‐18 serum concentrations are associated in apparently healthy humans with plasma concentrations of various LCTs. IL‐18 could contribute to the development of liver disease associated with insulin resistance.     

Lipocalin-2: development, analytical characterization, and clinical testing of a new ELISA.

Lipocalin-2 (also known as neutrophil gelatinase-associated lipocalin [NGAL]) has been described as a promising marker of metabolic syndrome associated with inflammation. The aim of our work was to develop an assay for the determination of lipocalin-2 in human serum and to investigate its levels in healthy volunteers and donors suffering from metabolic syndrome. We also conducted a pilot study on individuals with metabolic syndrome and on healthy probands and measured lipocalin-2 in these individuals. We developed and evaluated the sandwich ELISA method for the quantitative determination of human lipocalin-2 in serum samples. We measured blood pressure, waist circumference, serum cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, insulin, glucose, creatinine, hs-CRP, and adiponectin and calculated the BMI and Quicki insulin sensitivity index. In the study on 153 healthy volunteers, we showed that sex and age are not determinative for lipocalin-2 serum values. Furthermore, we tested 45 individuals with metabolic syndrome; values of lipocalin-2 did not differ (78.8 vs. 80.0 microg/l, p =0.56) from the data of healthy individuals from the first study. Neither group differed with regard to sex or age. Lipocalin-2 correlated with alanine aminotransferase (ALT) (r=-0.3, p<0.01) aspartate aminotransferase (AST) (r=-0.3, p<0.01), cholesterol (r=-0.21, p=0.047), creatinine (r=0.19, p=0.05), and high-sensitivity C-reactive protein (hs-CRP) (r=0.22, p=0.036). No significant correlation was found between serum lipocalin-2 and BMI, waist circumference, blood pressure, triglycerides, HDL, Quicki, or the number of metabolic syndrome components. When study patients with metabolic syndrome were further stratified according to the number of components of metabolic syndrome, serum concentrations of lipocalin-2 did not differ. The results presented demonstrate the analytical competence of the lipocalin-2 assay. However, we assumed that lipocalin-2 is not a routinely usable marker of metabolic syndrome or obesity. The association between serum lipocalin-2 and obesity or metabolic syndrome was not validated in our study.     

Oxidative stress in the pathogenesis of nonalcoholic fatty liver disease,in rats fed with a choline-deficient diet

Background/Aim : The pathogenesis of Nonalcoholic Fatty Liver Disease remains largely unknown, but oxidative stress seems to be involved. The aim of this study was to evaluate the role of oxidative stress in experimental hepatic steatosis induced by a choline-deficient diet. Methods : Fatty liver disease was induced in Wistar rats by a choline-deficient diet. The animals were randomized into three groups: I (G1) and II (G2), n=6 each - fed with a choline-deficient diet for four and twelve weeks respectively; Group III (control-G3; n=6) - fed with a standard diet for twelve weeks. Samples of plasma and liver were submitted to biochemical, histological and oxidative stress analysis. Variables measured included serum levels of aminotransferases (AST, ALT), cholesterol and triglycerides. Oxidative stress was measured by lucigenin-enhanced luminescence and the concentration of hydroperoxides (CE-OOH-cholesteryl ester) in the liver tissue. Results: We observed moderate macro- and microvesicular fatty change in periportal zones G1 and G2 as compared to controls (G3). In G2, fatty change was more severe. The inflammatory infiltrate was scanty and no fibrosis was seen in any group. There was a significant increase of AST and triglycerides in G1 and G2 as compared to control group G3. The lucigenin-amplified luminescence (cpm/mg/min × 10³) was significantly increased in G1 (1393±790) and G2 (7191±500) as compared to controls (513±170), p <0.05. The concentrations of CE-OOH were higher in G1 (5.7±0.9 nmol/mg protein) as compared to control (2.6±0.7 nmol/mg protein), p <0.05. Conclusion: 1) Oxidative stress was found to be increased in experimental liver steatosis; 2) The production of reactive oxygen species was accentuated when liver steatosis was more severe; 3) The alterations produced by oxidative stress could be an important step in the pathogenesis of nonalcoholic fatty liver disease.     

Increased production of IL-1alpha and TNF-alpha in lipopolysaccharide-stimulated blood from obese patients with non-alcoholic fatty liver disease

Enhanced pro-inflammatory cytokine production is considered a pathogenic factor in non-alcoholic fatty liver disease (NAFLD). Peripheral blood production of interleukin-1alpha (IL-1alpha) and tumor necrosis factor-alpha (TNF-alpha) was studied in relation to the severity of histological changes of the liver in obese NAFLD patients. Basal levels in serum and production of IL-1alpha and TNF-alpha in peripheral blood cell cultures after stimulation with lipopolysaccharide (enzyme-linked immunoabsorbent assays) were measured in 11 patients with steatosis and 15 with steatohepatitis, who underwent gastrectomy with a gastro-jejunal anastomosis in roux and Y, and in 9 controls who underwent anti-reflux surgery. Production of IL-1alpha and TNF-alpha was 122 and 67% higher in patients with steatosis than control values, respectively. In patients with steatohepatitis, IL-1alpha production was 300 and 80% higher and that of TNF-alpha 110 and 26% higher, as compared with controls and steatosis patients, respectively. Production of IL-1alpha was positively correlated with that of TNF-alpha (r=0.78, p<0.0001). IL-1alpha and TNF-alpha production were both positively correlated with the degree of steatosis (r=0.68, p<0.001 and r=0.74, p<0.0001) and steatohepatitis (r=0.77 and r=0.75, p<0.0001) at liver biopsy, and with the homeostasis model assessment index (r=0.73, p<0.0001 and r=0.63, p<0.01), respectively. Basal serum IL-1alpha and TNF-alpha levels were comparable in the three groups studied. It is concluded that elevated production of IL-1alpha and TNF-alpha by in vitro stimulated whole blood cell cultures occurs in NAFLD obese patients, which might play a pathophysiological role upon inflammatory leukocyte infiltration of the liver.     

Plasma tumor necrosis factor-alpha levels and insulin resistance in nondiabetic hypertensive subjects

OBJECTIVES: Tumor necrosis factor-alpha (TNF-alpha) is associated with insulin resistance in certain conditions. However, whether TNF-alpha is related to insulin resistance in hypertensive subjects is still controversial. The aim of this study was to determine the status of TNF-alpha and insulin resistance in hypertension. METHODS: Newly diagnosed nondiabetic 17 essentially hypertensive (6 men, 11 women) patients, and 11 control healthy subjects (5 men, 6 women) are involved in the study. Body mass index (BMI), insulin, fasting blood glucose, cholesterol, triglyceride, and TNF-alpha levels were measured. Insulin resistance is assessed according to homeostasis model of assessment (HOMA-IR). RESULTS: Serum insulin (8.4 +/- 2.7 vs. 6.1 +/- 1.4 mIU/ml; p < 0.01), triglyceride (245.0 +/- 39.9 vs. 193.0 +/- 22.8 mg/dl; p < 0.01), and TNF-alpha (4.2 +/- 0.7 vs. 3.0 +/- 0.6 pg/ml; p < 0.001) levels, and HOMA-IR (2.0 +/- 0.8 vs. 1.3 +/- 0.3; p < 0.001) were significantly higher in the hypertensive patients compared to the normotensive control group. There were positive correlations between TNF-alpha levels and body mass index (r = 0.64, p < 0.01), and triglyceride (r = 0.55 p = 0.02) levels in the whole study group. However, there was no correlation of either TNF-alpha or HOMA-IR. CONCLUSIONS: Our data revealed that hypertensive patients have insulin resistance and higher TNF-alpha levels, but there is no relation between TNF-alpha levels and insulin resistance.     

自噬抑制剂氯喹对急性酒精诱导小鼠肝损伤的影响

目的：探讨自噬抑制剂氯喹（CQ）对急性酒精诱导肝损伤的影响及其作用机制。方法：将雄性C57BL/6小鼠随机分为3组：正常对照组、酒精组、氯喹干预组（n=7）,其中酒精组按4.5 g/kg剂量给予33%（V/V）酒精灌胃。HE和油红O染色检测各组小鼠肝组织脂滴变化;检测肝组织甘油三酯（TG）含量变化;检测血清谷草转氨酶（AST）和谷丙转氨酶（ALT）活性;免疫荧光法检测微管相关蛋白轻链3（LC3）蛋白变化;Western blot法检测LC3蛋白和核蛋白P65表达的变化;ELISA法检测促炎因子TNF-α、IL-6的变化。结果：与对照组比较,酒精组脂滴形成、TG含量、血清AST和ALT活性明显增高。与对照组比较,酒精组LC3-Ⅱ蛋白表达明显增加;与酒精组比较,氯喹干预组使酒精诱导的LC3-Ⅱ蛋白表达增强进一步加剧,使酒精诱导的TG含量、血清AST和ALT活性进一步增高,同时增加了酒精诱导的p65入核及TNFα、IL-6释放。结论：急性酒精能引起小鼠肝脏脂肪变化及炎症,而自噬抑制剂氯喹抑制自噬进程,加剧酒精诱导的肝损伤,说明自噬在酒精诱导肝损伤中可能具有保护效应。     

Zinc status in plasma of obese individuals during glucose administration

To know whether plasma zinc status is altered under acute hyperglycemic state, the interrelationships among plasma glucose, insulin, and zinc concentrations during oral glucose tolerance test (OGTT) in obese individuals and their lean controls were studied. Plasma glucose and insulin concentrations under fasting as well as those values in response to OGTT were significantly higher in obese individuals than those in lean controls. On the other hand, the obese had lower fasting plasma zinc concentrations compared to lean controls (13.5 vs 18.1 Μmol/L,p < 0.005). Under fasting, plasma zinc concentrations in overall individuals inversely correlated to their body mass index (BMI) (r = -0.516), plasma glucose (r = -0.620), and plasma insulin (r = -0.510). However, there were no significant changes in plasma zinc and copper values during OGTT in both obese individuals and lean controls. This study showed that plasma zinc values had no changes during OGTT in obese individuals. The results also indicated that lower fasting plasma zinc concentrations in obese individuals were not the short-term metabolic result.     

Coffee,tea, and plasma cholesterol: the Jerusalem Lipid Research Clinic prevalence study.

The association of intake of coffee and tea, assessed by 24 hour dietary recall, with plasma cholesterol and its lipoprotein fractions was studied in a sample of 1007 men and 589 women aged 35-64 resident in Jerusalem. These cross sectional data showed a significant linear association (p less than 0.001) between consumption of coffee in men and plasma cholesterol and low density lipoprotein cholesterol concentrations. Men who drank five cups of coffee or more had plasma cholesterol concentrations about 0.5 mmol/l (20 mg/100 ml) higher than non-drinkers after controlling for age, ethnicity, body mass, education, season of year, smoking, tea drinking, and dietary intake of fat and carbohydrates. In women adjusted mean plasma cholesterol concentration was 0.34 mmol/l (13 mg/100 ml) higher in coffee drinkers grouped together (p less than 0.01). The test for a linear trend was not significant. The association in both sexes was largely with the low density lipoprotein cholesterol fraction. High density lipoprotein cholesterol concentrations were somewhat increased in women who drank coffee (p less than 0.01 for a linear trend) but not in men. Tea drinking was not associated with unadjusted plasma cholesterol concentrations in either sex. Male tea drinkers, but not female, had slightly higher adjusted plasma cholesterol concentrations than non-drinkers (0.15 mmol/l (6 mg/100 ml), p = 0.04). No dose response relation was evident. In this population, characterised by a low intake of saturated fatty acids and relatively low mean plasma cholesterol concentrations, coffee drinking may be a determinant of low density lipoprotein cholesterol concentrations.     

Hepatic steatosis and plasma dyslipidemia induced by a high-sucrose diet are corrected by an acute leptin infusion.

High sucrose (HS) feeding in rats induces hepatic steatosis and plasma dyslipidemia. In previous reports (Huang W, Dedousis N, Bhatt BA, O'Doherty RM. J Biol Chem 279: 21695-21700, 2004; and Huang W, Dedousis N, Bandi A, Lopaschuk GD, O'Doherty RM. Endocrinology 147: 1480-1487, 2006), our laboratory demonstrated a rapid ( approximately 100 min) leptin-induced decrease in liver and plasma VLDL triglycerides (TG) in lean rats, effects that were abolished in obese rats fed a high-fat diet, a model that also presents with hepatic steatosis and plasma dyslipidemia. To further examine the capacity of acute leptin treatment to improve metabolic abnormalities induced by nutrient excess, hepatic leptin action was studied in rats after 5 wk of HS feeding. HS feeding induced hepatic steatosis (TG+80+/-8%; P=0.001), plasma hyperlipidemia (VLDL-TG+102+/-14%; P=0.001), hyperinsulinemia (plasma insulin +67+/-12%; P=0.04), and insulin resistance as measured by homeostasis model assessment (+125+/-20%; P=0.02), without increases in adiposity or plasma leptin concentration compared with standard chow-fed controls. A 120-min infusion of leptin (plasma leptin 13.6+/-0.7 ng/ml) corrected hepatic steatosis (liver TG-29+/-3%; P=0.003) and plasma hyperlipidemia in HS (VLDL-TG-42+/-4%; P=0.001) and increased plasma ketones (+45+/-3%; P=0.006), without altering plasma glucose, insulin, or homeostasis model assessment compared with saline-infused HS controls. In addition, leptin activated liver phosphatidylinositol 3-kinase (+70+/-18%; P=0.01) and protein kinase B (Akt; +90+/-29%; P=0.02), and inhibited acetyl-CoA carboxylase (40+/-7%; P=0.04) in HS, further demonstrating that hepatic leptin action was intact in these animals. We conclude that 1) leptin action on hepatic lipid metabolism remains intact in HS-fed rats, 2) leptin rapidly reverses hepatic steatosis and plasma dyslipidemia induced by sucrose, and 3) the preservation of hepatic leptin action after a HS diet is associated with the maintenance of low adiposity and plasma leptin concentrations.     

TNF-alpha and leptin in experimental liver fibrosis models induced by carbon tetrachloride and by common bile duct ligation

In this study we investigated TNF-alpha and leptin levels in two different liver fibrosis models induced by carbon tetrachloride (CCl(4)) and common bile duct ligation (CBDL). A total of 36 male rats of Albino-Wistar strain were allocated to three groups. One of the groups was the control. The second group received 0.15 ml 100 g(-1) CCl(4) subcutaneously for 6 weeks, 3 days per week. The third group underwent common bile duct ligation (CBDL) and was monitored for 4 weeks. Histopathological investigation included fibrosis, steatosis and inflammation. Serum IL-6 and TNF-alpha levels were analysed by ELISA methods and leptin was analysed by RIA. Fibrosis and steatosis increased significantly in the CCl(4) group in comparison with the CBDL group (p < 0.01; p < 0.001). Leptin and TNF-alpha levels in CCl(4) group were higher than those in the CBDL and control groups (p < 0.05). TNF-alpha and leptin levels were not related to each another in either the CCl(4) group or the CBDL group (r=0.22, p > 0.05; r=0.19, p > 0.05). The IL-6 level was higher in the CCl(4) group in relation to severity of inflammation (p < 0.05). TNF-alpha and leptin levels were higher in animals with liver fibrosis induced by CCl(4), than they were in those whose liver fibrosis was induced by common bile duct ligation. Leptin and TNF-alpha may be less effective on the development of liver fibrosis in the group which underwent common bile duct ligation.