Vascular smooth muscle responsiveness to nitric oxide is reduced in healthy adults with increased adiposity

Vascular smooth muscle responsiveness to nitric oxide, as assessed by nitroglycerin-induced dilation (NID), is impaired in clinical cardiovascular disease, but its relation to adiposity is unknown. We determined the relation of NID to total and abdominal adiposity in healthy adults varying widely in adiposity. In 224 men and women [age, 18-79 years; body mass index (BMI), 16.4-42.2 kg/m(2)], we measured NID (brachial artery dilation to 0.4 mg sublingual nitroglycerin), total body adiposity [BMI and percent body fat (percent BF via dual-energy X-ray absorptiometry)], and indexes of abdominal adiposity [waist circumference (WC) and waist-to-hip ratio (WHR)]. In a subgroup (n = 74), we also measured total abdominal fat (TAF), abdominal visceral fat (AVF), and subcutaneous fat (ASF) using computed tomography. Based on multiple linear regression, NID was negatively related to BMI [part correlation coefficient (r(part)) = -0.19, P = 0.004] and abdominal adiposity (WC, r(part) = -0.22; WHR, r(part) = -0.19; TAF, r(part) = -0.36; AVF, r(part) = -0.36; and ASF, r(part) = -0.30; all P ≤ 0.009) independent of sex, but only tended to be related to total percent BF (r(part) = -0.12, P = 0.07). In a subgroup of subjects with the highest compared with the lowest amount of AVF, NID was 35% lower (P = 0.003). Accounting for systolic blood pressure, HDL cholesterol, glucose, insulin resistance, adiponectin, and brachial artery diameter reduced or abolished some of the relations between NID and adiposity. In conclusion, NID is or tends to be negatively associated with measures of total adiposity (BMI and percent BF, respectively) but is consistently and more strongly negatively associated with abdominal adiposity. Adiposity may influence NID in part via other cardiovascular risk factors.     

Leptin,insulin and thyroid hormones in a cohort of Egyptian obese Down syndrome children: a comparative study

Oxidative stress has been implicated in the development of type 2 diabetes mellitus. Bilirubin is a potent endogenous antioxidant, and coffee is a major source of exogenous antioxidants. Serum gamma-glutamyltransferase (GGT), a marker of oxidative stress, is a strong predictor of the risk of type 2 diabetes mellitus. This study evaluated the effect modification of bilirubin and coffee consumption on the association of serum GGT with glycated hemoglobin (HbA1c) and the combined effect of bilirubin and coffee on HbA1c concentrations. The subjects were 4492 men and 6242 women aged 49–76 years who participated in the baseline survey of an on-going cohort study on lifestyle-related diseases in Fukuoka, Japan. Geometric means of HbA1c were examined according to quartile categories of GGT, with stratification by serum total bilirubin (≥ 0.6 mg/dL versus less in men and ≥ 0.5 mg/dL versus less in women) and coffee consumption (< 1, 1–3 and ≥ 4 cups of per day). Statistical adjustment was made for age, smoking, alcohol use and body mass index by using analysis of covariance. HbA1 concentrations increased progressively with increasing levels of GGT in both men and women. The increasing trend of HbA1c concentrations associated with GGT did not differ by either bilirubin status or coffee consumption. Both men and women with high bilirubin had consistently lower concentrations of HbA1c across the GGT quartiles. Higher coffee consumption was associated with lower concentrations of HbA1c in women with low bilirubin (trend P = 0.04), but not with high bilirubin (trend P = 0.37). There was no such association between coffee and HbA1c in men with either low or high bilirubin levels. Bilirubin is possibly protective against deterioration of glucose metabolism. Further studies are needed regarding the combined effect of bilirubin and coffee on glucose metabolism.     

Influence of endurance exercise training and sex on intramyocellular lipid and mitochondrial ultrastructure, substrate use, and mitochondrial enzyme activity

Impaired mitochondrial function and structure and intramyocellular lipid (IMCL) accumulation have been associated with obesity and Type 2 diabetes. We examined whether endurance exercise training and sex influenced IMCL and mitochondrial morphology using electron microscopy, whole-body substrate use, and mitochondrial enzyme activity. Untrained men (n = 5) and women (n = 7) were tested before and after 7 wk of endurance exercise training. Testing included 90 min of cycle ergometry at 60% Vo(2 peak) with preexercise muscle biopsies analyzed for IMCL and mitochondrial size/area using electron microscopy and short-chain beta-hydroxyacyl-CoA dehydrogenase (SCHAD) and citrate synthase (CS) enzyme activity. Training increased the mean lipid area density (P = 0.090), the number of IMCL droplets (P = 0.055), the number of IMCL droplets in contact with mitochondria (P = 0.010), the total mitochondrial area (P < 0.001), and the size of individual mitochondrial fragments (P = 0.006). Women had higher mean lipid area density (P = 0.030) and number of IMCL droplets (P = 0.002) before and after training, but higher individual IMCL area only before training (P = 0.013), compared with men. Women oxidized more fat (P = 0.027) and less carbohydrate (P = 0.032) throughout the study. Training increased Vo(2 peak) (P < 0.001), %fat oxidation (P = 0.018), SCHAD activity (P = 0.003), and CS activity (P = 0.042). In summary, endurance exercise training increased IMCL area density due to an increase in the number of lipid droplets, whereas the increase in total mitochondrial area was due to an increase in the size of individual mitochondrial fragments. In addition, women have higher IMCL content compared with men due mainly to a greater number of individual droplets. Finally, endurance exercise training increased the proportion of IMCL in physical contact with mitochondria.     

Attenuation of skeletal muscle and strength in the elderly: The Health ABC Study.

Although loss of muscle mass is considered a cause of diminished muscle strength with aging, little is known regarding whether composition of aging muscle affects strength. The skeletal muscle attenuation coefficient, as determined by computed tomography, is a noninvasive measure of muscle density, and lower values reflect increased muscle lipid content. This investigation examined the hypothesis that lower values for muscle attenuation are associated with lower voluntary isokinetic knee extensor strength at 60 degrees/s in 2,627 men and women aged 70-79 yr participating in baseline studies of the Health ABC Study, a longitudinal study of health, aging, and body composition. Strength was higher in men than in women (132.3 +/- 34.5 vs. 81.4 +/- 22.0 N x m, P < 0.01). Men had greater muscle attenuation values (37.3 +/- 6.5 vs. 34.7 +/- 7.0 Hounsfield units) and muscle cross-sectional area (CSA) at the midthigh than women (132.7 +/- 22.4 vs. 93.3 +/- 17.5 cm(2), P < 0.01 for both). The strength per muscle CSA (specific force) was also higher in men (1.00 +/- 0.21 vs. 0.88 +/- 0.21 N x m x cm(-2)). The attenuation coefficient was significantly lower for hamstrings than for quadriceps (28.7 +/- 8.7 vs. 41.1 +/- 6.9 Hounsfield units, P < 0.01). Midthigh muscle attenuation values were lowest (P < 0.01) in the eldest men and women and were negatively associated with total body fat (r = -0.53, P < 0.01). Higher muscle attenuation values were also associated with greater specific force production (r = 0.26, P < 0.01). Multivariate regression analysis revealed that the attenuation coefficient of muscle was independently associated with muscle strength after adjustment for muscle CSA and midthigh adipose tissue in men and women. These results demonstrate that the attenuation values of muscle on computed tomography in older persons can account for differences in muscle strength not attributed to muscle quantity.     

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.     

IMCL area density, but not IMCL utilization, is higher in women during moderate-intensity endurance exercise, compared with men

Women use more fat during endurance exercise as evidenced by a lower respiratory exchange ratio (RER). The contribution of intramyocellular lipid (IMCL) to lipid oxidation during endurance exercise is controversial, and studies investigating sex differences in IMCL utilization have found conflicting results. We determined the effect of sex on net IMCL use during an endurance exercise bout using an ultrastructural evaluation. Men (n = 17) and women (n = 19) completed 90-min cycling at 63% Vo(2peak). Biopsies were taken before and after exercise and fixed for electron microscopy to determine IMCL size, # IMCL/area, IMCL area density, and the % IMCL touching mitochondria. Women had a lower RER and carbohydrate oxidation rate and a higher lipid oxidation rate during exercise (P < 0.05), compared with men. Women had a higher # IMCL/area and IMCL area density (P < 0.05), compared with men. Women, but not men, had a higher % IMCL touching mitochondria postexercise (P = 0.03). Exercise decreased IMCL area density (P = 0.01), due to a decrease in the # IMCL/area (P = 0.02). There was no sex difference in IMCL size or net use. In conclusion, women have higher IMCL area density compared with men, due to an increased # IMCL and not an increased IMCL size, as well as an increased % IMCL touching mitochondria postexercise. Endurance exercise resulted in a net decrease in IMCL density due to decreased number of IMCL, not decreased IMCL size, in both sexes.     

Fatty liver in type 2 diabetes mellitus: relation to regional adiposity,fatty acids,and insulin resistance

The current study was undertaken to examine metabolic and body composition correlates of fatty liver in type 2 diabetes mellitus (DM). Eighty-three men and women with type 2 DM [mean body mass index (BMI): 34 +/- 0.5 kg/m2] and without clinical or laboratory evidence of liver dysfunction had body composition assessments of fat mass (FM), visceral adipose tissue (VAT), liver and spleen computed tomography (CT) attenuation (ratio of liver to spleen), muscle CT attenuation, and thigh adiposity; these assessments were also performed in 12 lean and 15 obese nondiabetic volunteers. Insulin sensitivity was measured with a euglycemic insulin infusion (40 mU. m-2. min-1) combined with systemic indirect calorimetry to assess glucose and lipid oxidation, and with infusions of [2H2]glucose for assessment of endogenous glucose production. A majority of those with type 2 DM (63%) met CT criteria for fatty liver, compared with 20% of obese and none of the lean nondiabetic volunteers. Fatty liver was most strongly correlated with VAT (r = -0.57, P < 0.0001) and less strongly but significantly associated with BMI (r = -0.42, P < 0.001) and FM (r = -0.37, P < 0.001), but only weakly associated with subcutaneous adiposity (r = -0.29; P < 0.01). Fatty liver was also correlated with subfascial adiposity of skeletal muscle (r = -0.44; P < 0.01). Volunteers with type 2 DM and fatty liver were substantially more insulin resistant those with type 2 DM but without fatty liver (P < 0.001) and had higher levels of plasma free fatty acids (P < 0.01) and more severe dyslipidemia (P < 0.01), a pattern observed in both genders. Plasma levels of cytokines were increased in relation to fatty liver (r = -0.34; P < 0.01). In summary, fatty liver is relatively common in overweight and obese volunteers with type 2 DM and is an aspect of body composition related to severity of insulin resistance, dyslipidemia, and inflammatory markers.     

Green tea extract attenuates hepatic steatosis by decreasing adipose lipogenesis and enhancing hepatic antioxidant defenses in ob/ob mice

Excess hepatic lipid accumulation and oxidative stress contribute to nonalcoholic fatty liver disease (NAFLD). Thus, we hypothesized that the hypolipidemic and antioxidant activities of green tea extract (GTE) would attenuate events leading to NAFLD. Obese mice (ob/ob; 5 weeks old, n=38) and their lean littermates (n=12) were fed 0%, 0.5% or 1% GTE for 6 weeks. Then, hepatic steatosis, oxidative stress and inflammatory markers were measured. Obese mice, compared to lean controls, had greater hepatic lipids and serum alanine aminotransferase (ALT). GTE at 1% lowered (P<.05) hepatic lipids and ALT in obese mice. The GTE-mediated attenuation in hepatic steatosis was accompanied by decreased mRNA expression of adipose sterol regulatory element-binding protein-1c, fatty acid synthase, stearoyl CoA desaturase-1, and hormone-sensitive lipase and decreased serum nonesterified fatty acid concentrations. Immunohistochemical data indicated that steatotic livers from obese mice had extensive accumulation of tumor necrosis factor-α (TNF-α), whereas GTE at 1% decreased hepatic TNF-α protein and inhibited adipose TNF-α mRNA expression. Hepatic total glutathione, malondialdehyde and Mn- and Cu/Zn-superoxide dismutase activities in obese mice fed GTE were normalized to the levels of lean littermates. Also, GTE increased hepatic catalase and glutathione peroxidase activities, and these activities were inversely correlated with ALT and liver lipids. Collectively, GTE mitigated NAFLD and hepatic injury in ob/ob mice by decreasing the release of fatty acids from adipose and inhibiting hepatic lipid peroxidation as well as restoring antioxidant defenses and decreasing inflammatory responses. These findings suggest that GTE may be used as an effective dietary strategy to mitigate obesity-triggered NAFLD.     

Distribution of subcutaneous fat predicts insulin action in obesity in sex-specific manner

The pattern of adipose tissue (AT) distribution is an important predictor of metabolic risk. The aim of this study was to analyze the association of peripheral (insulin-mediated glucose disposal--M) and hepatic (suppression of endogenous glucose production--EGP) insulin action with abdominal (subcutaneous abdominal AT-SAAT intraabdominal AT-IAAT) and thigh AT depots in obese individuals. Fifty-seven Pima Indians with normal glucose tolerance underwent magnetic resonance imaging (MRI) and euglycemic-hyperinsulinemic clamp. M was negatively related to intraperitoneal IAAT (P = 0.02) and deep SAAT (P = 0.03). Suppression of EGP was negatively related to total (P < 0.05) or deep SAAT (P < 0.05 and P = 0.01, respectively), and total or intraperitoneal IAAT (P = 0.009 and P = 0.002, respectively). A significant interaction with sex was found in the association between superficial SAAT and M, so that in women, but not men, M negatively correlated with superficial SAAT (P = 0.02). In stepwise regression analysis, both M (r2 = 0.09) and EGP suppression (r2 = 0.17) were associated only with intraperitoneal IAAT in the whole group. In the sex-specific analysis (because of the significant interaction), lower M was associated with higher deep SAAT (r2 = 0.15) in combination with lower superficial SAAT (r2 = 0.09) in men, and with higher superficial SAAT (r2 = 0.29) in combination with lower thigh subcutaneous AT (r2 = 0.16) in women. Although intraperitoneal IAAT and deep SAAT were major predictors of peripheral and hepatic insulin action in obese Pima Indians, the largest variance in M rate was explained in a sex-specific manner by relative size of subcutaneous AT depots.     

原发性高血压患者α-Adducin基因单核苷酸多态性(Gly460Trp)与血清胆红素含量相关性

探讨了自 2 0 0 0年 9月到 2 0 0 1年 1月来自安徽省霍邱县地区原发性高血压人群中α Adducin基因单核苷酸多态性与血清中总胆红素、直接胆红素和间接胆红素含量的相关性。在原发性高血压女性患者中 ,在校正了许多可能影响胆红素含量的重要因素后 ,与携带有Gly4 6 0Gly基因型的高血压女性患者相比较 ,携带有Trp4 6 0Trp基因型的高血压女性患者血清平均总胆红素 (β =- 1 2 μmol/L ;P =0 0 1)、直接胆红素 (β =- 0 4 μmol/L ;P =0 0 2 )和间接胆红素 (β=- 0 8μmol/L ;P =0 0 3)的含量比较低。在女性中抽取总胆红素、直接胆红素和间接胆红素含量最高和最低的各 2 5 % ,在校正了重要的变量后发现携带Trp/Trp基因型的女性比Gly4 6 0Gly基因型的女性有更大的可能性血清总胆红素含量 (OR值 =4 0 ;95 %可信区间 :1 6～ 10 2 ;P <0 0 1)、直接胆红素含量 (OR值 =4 0 ;95 %可信区间 :1 6～ 9 7;P <0 0 1)和间接胆红素含量 (OR值 =2 7;95 %可信区间 :1 1～ 6 7;P =0 0 3)更低。然而 ,在男性高血压患者中没有发现任何明显的相关性。以上的结果认为在中国原发性高血压女性患者中 ,Trp/Trp基因型与低的血清胆红素含量有直接关系 ,因为Trp/Trp基因型的女性的低血清胆红素 ,进而认为也许增加了患心血     

脐带间充质干细胞对内毒素血症诱发的大鼠急性肝功能损伤的影响

目的评价脐带间充质干细胞（hUC-MSCs）对内毒素血症诱发的大鼠急性肝功能损伤的影响及其与凋亡机制的关系。 方法6周龄雄性SD大鼠18只,随机分为3组,分别是对照组（C组）、内毒素血症组（M组）和内毒素血症+hUC-MSCs治疗组（M+cells组）,每组6只。大鼠腹腔注射5 mg/kg脂多糖（LPS）诱导内毒素血症模型,并经尾静脉注射含20×10⁶个hUC- MSCs。4 h时检测血清谷草转氨酶（AST）和谷丙转氨酶（ALT）,ELISA方法检测肿瘤坏死因子（TNF-α）、白细胞介素6（IL-6）,HE常规染色鉴定肝脏组织病理,Western Blot法检测肝脏组织抗凋亡蛋白Bcl-2、促凋亡蛋白Bax、凋亡信号调节激酶1（ASK1）、应激活化蛋白激酶即JUN氨基末端激酶（JNK）蛋白的表达。多组间比较采用单因素方差分析,相关分析选用pearson。 结果（1）C组AST、ALT、TNF-α和IL-6浓度分别为（74.66±6.39）U/ L、（40.07±6.07）U/ L、（37.74±3.08）ng/L和（0.42±0.07）ng/L;与M组比较（310.75±9.13）U/L、（107.04±10.04）U/ L、（160.32±4.88）ng/L和（0.90±0.09）ng/L,差异具有统计学意义（P均 < 0.05）,M组AST、ALT、TNF-α、IL-6浓度分别为（310.75±9.13）U/L、（107.04±10.04）U/ L、（160.32±4.88）ng/ L和（0.90±0.09）ng/L,与M+cells组比较（204.49±15.36）U/L、（71.24± 7.34）U/ L、（117.61±9.37）ng/ L和（0.60±0.10）ng/L,差异具有统计学意义（P均 < 0.05）。（2）C组大鼠肝细胞形态正常,可见肝小叶结构清晰,肝汇管区无炎性细胞浸润,M组大鼠肝小叶散在点状坏死肝细胞伴炎性浸润,肝细胞间隙散布增生的Kuffer细胞,M+cells组大鼠肝小叶炎性细胞浸润及肝细胞间隙Kuffer细胞浸润改善。（3）与C组比较,M组大鼠肝脏组织JUN、ASK1和Bax蛋白表达均增高（P均 < 0.05）,Bcl-2蛋白表达降低（P < 0.05）;与M组比较,M+cells组大鼠肝脏组织JUN、ASK1和Bax蛋白表达降低（P均 < 0.05）,Bcl-2蛋白增加（P < 0.05）。（4）单因素相关分析显示大鼠血清ALT、AST与TNF-a指数呈正相关（r值分别为0.9580、0.9865,P均< 0.05）,大鼠血清ALT、AST与IL-6指数呈正相关（r值分别为0.9892、0.9630,P均 < 0.05）,大鼠血清ALT、AST分别与BAX、ASK1、JNK指数均呈正相关（r值分别为0.9993、0.9851、0.7901、0.9864、0.9557、0.7128,P均 < 0.05）,大鼠血清ALT、AST分别与BCL-2指数均呈负相关（r值分别为-0.8824、-0.9338,P均 < 0.05）,大鼠血清TNF-α分别与BAX、ASK1、JNK指数均呈正相关（r值分别为0.9466、0.8958、0.6025,P均< 0.05）,大鼠血清TNF-α与BCL-2指数呈负相关（r = -0.6025,P均 < 0.05）,大鼠血清IL-6分别与BAX、ASK1、JNK指数均呈正相关（r值分别为0.9941、0.9997、0.8679,P均< 0.05）,大鼠血清IL-6与BCL-2指数呈负相关（r = -0.8078,P均 < 0.05）。 结论hUC-MSCs具有减轻内毒素血症大鼠急性肝功能损伤的作用,其机制与抑制肝脏细胞凋亡相关。     

Exercise training enhances leg vasodilatory capacity of 65-yr-old men and women

To determine whether extremity vasodilatory capacity may be augmented in older persons by endurance exercise training, lower leg blood flow and conductance were characterized plethysmographically at rest and during maximal hyperemia in 9 men and 10 women aged 64 +/- 3 (SD) yr before and after 31 +/- 6 wk of walking and jogging at 70-90% of maximal oxygen uptake for 45 min 3-5 days/wk. Maximal oxygen uptake expressed as milliliters per kilogram per minute improved 25% in men and 21% in women (P less than 0.01). Maximal leg blood flow and conductance increased in all nine men by an average of 39 +/- 33 (P less than 0.001) and 42 +/- 44% (P less than 0.004), respectively. Results were more variable in women and achieved unequivocal statistical significance only for maximal blood flow (+33 +/- 54% for blood flow and +29 +/- 55% for conductance; P less than 0.02 and P = 0.05, respectively). Body weight and skinfold adiposity declined in both sexes (P less than 0.05). Enhancement of vasodilatory capacity was related to weight loss in men and adipose tissue loss in women (r = 0.61 and 0.51, respectively; P less than 0.05). There were no significant changes in exercise capacity, body weight, or maximal blood flow in four male and three female controls aged 66 +/- 4 yr. Thus adaptability of the lower limb circulation to endurance exercise training is retained to at least age 65 yr.     

胆道闭锁患儿血清GPC3、TGF-β1和VEGF水平与肝硬度值和肝功能的关系研究

目的:研究胆道闭锁(BA)患儿血清磷脂酰肌醇蛋白聚糖3(GPC3)、转化生子因子β1(TGF-β1)和血管内皮生长因子(VEGF)水平与肝硬度值和肝功能的关系。方法:选择2016月3月-2019年3月期间在我院接受Kasai手术治疗的62例BA患儿作为研究对象(BA组),并根据总胆红素水平分为黄疸患儿(总胆红素≥34.2μmol/L)、无黄疸患儿(总胆红素<34.2μmol/L);另取同期在本院体检的50例健康儿童作为对照组。检测BA组患儿术后2个月、对照组儿童体检时的血清GPC3、TGF-β1、VEGF及肝功能指标白蛋白(ALB)、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、γ-谷氨酰转肽酶(GGT)的水平及肝硬度值,采用Pearson相关分析血清GPC3、TGF-β1和VEGF水平与肝硬度值和肝功能的相关性。结果:BA组患儿的血清GPC3、TGF-β1、VEGF、ALT、AST、GGT水平及肝硬度值均明显高于对照组(P<0.05),血清ALB水平与对照组比较无统计学差异(P>0.05);BA组中黄疸患儿的血清GPC3、TGF-β1、VEGF、ALT、AST、GGT水平及肝硬度值均明显高于无黄疸患儿,血清ALB水平明显低于无黄疸患儿(P<0.05);BA组中血清GPC3、TGF-β1、VEGF水平与血清ALT、AST、GGT水平及肝硬度值呈正相关(P<0.05),与血清ALB水平呈负相关(P<0.05)。结论:BA患儿术后GPC3、TGF-β1和VEGF的升高与肝纤维化进程、肝功能破坏有关,未来可能成为研究BA术后肝纤维化发生机制的靶点。     

Skeletal muscle attenuation determined by computed tomography is associated with skeletal muscle lipid content.

The purpose of this investigation was to validate that in vivo measurement of skeletal muscle attenuation (MA) with computed tomography (CT) is associated with muscle lipid content. Single-slice CT scans performed on phantoms of varying lipid concentrations revealed good concordance between attenuation and lipid concentration (r(2) = 0.995); increasing the phantom's lipid concentration by 1 g/100 ml decreased its attenuation by approximately 1 Hounsfield unit (HU). The test-retest coefficient of variation for two CT scans performed in six volunteers was 0.51% for the midthigh and 0.85% for the midcalf, indicating that the methodological variability is low. Lean subjects had significantly higher (P < 0.01) MA values (49.2 +/- 2.8 HU) than did obese nondiabetic (39.3 +/- 7.5 HU) and obese Type 2 diabetic (33.9 +/- 4. 1 HU) subjects, whereas obese Type 2 diabetic subjects had lower MA values that were not different from obese nondiabetic subjects. There was also good concordance between MA in midthigh and midcalf (r = 0.60, P < 0.01), psoas (r = 0.65, P < 0.01), and erector spinae (r = 0.77, P < 0.01) in subsets of volunteers. In 45 men and women who ranged from lean to obese (body mass index = 18.5 to 35.9 kg/m(2)), including 10 patients with Type 2 diabetes mellitus, reduced MA was associated with increased muscle fiber lipid content determined with histological oil red O staining (P = -0.43, P < 0. 01). In a subset of these volunteers (n = 19), triglyceride content in percutaneous biopsy specimens from vastus lateralis was also associated with MA (r = -0.58, P = 0.019). We conclude that the attenuation of skeletal muscle in vivo determined by CT is related to its lipid content and that this noninvasive method may provide additional information regarding the association between muscle composition and muscle function.     

Selected genetic polymorphisms and plasma coagulation factor VII changes with exercise training.

We assessed the effects of coagulation factor VII (FVII) gene polymorphisms, lipid-related polymorphisms, and exercise training-induced plasma lipoprotein lipid changes on FVII level changes with exercise training in middle- to older-aged men and women. Forty-six healthy sedentary men and women were stabilized on a low-fat diet and then underwent baseline testing, 6 mo of endurance exercise training, and final testing. Plasma FVII-Ag levels decreased with exercise training (106.7 +/- 1.4 vs. 104.2 +/- 1.6%, P = 0.005). There were no significant differences in FVII-Ag changes with exercise training between -323 (0/10 bp)/-401 (G/T) haplotype or -402 (G/A) genotype groups. FVII-Ag changes with training were not correlated with changes in plasma lipoprotein lipids. In linear regression analyses, FVII-Ag changes with training remained significant after adjusting for training-induced plasma lipoprotein lipid changes (P = 0.01). FVII changes with training were associated with apolipoprotein E genotype (P = 0.012); this relationship was still evident after adjusting for training-induced plasma lipoprotein lipid changes (P = 0.047). FVII changes with training also were significantly associated with human ATPase binding cassette-1 genotype (P = 0.018); this relationship persisted after accounting for the effect of the training-induced plasma lipoprotein lipid changes (P = 0.045). We conclude that plasma FVII-Ag changes with exercise training are more closely related to selected lipid-related genotypes than FVII gene promoter variants.     

Evidence of LPL gene-exercise interaction for body fat and LPL activity: the HERITAGE Family Study.

Evidence of a gene-exercise interaction for traits related to body composition is limited. Here, the association between the lipoprotein lipase (LPL) S447X polymorphism and changes in body mass index, fat mass, percent body fat, abdominal visceral fat measured by computed tomography, and post-heparin plasma LPL activity in response to 20 wk of endurance training was investigated in 741 adult white and black subjects. Changes were compared between carriers and noncarriers of the X447 allele after adjustment for the effects of age and pretraining values. No evidence of association was observed in men. However, white women carrying the X447 allele exhibited greater reductions of body mass index (P = 0.01), fat mass (P = 0.01), and percent body fat (P = 0.03); in black women, the carriers exhibited a greater reduction of abdominal visceral fat (P = 0.05) and a greater increase in post-heparin LPL activity (P = 0.02). These results suggest that the LPL S447X polymorphism influences the training-induced changes in body fat and post-heparin LPL activity in women but not in men.     

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.     

Associations of maximal strength and muscular endurance test scores with cardiorespiratory fitness and body composition

The purpose of the present study was to assess the relationships between maximal strength and muscular endurance test scores additionally to previously widely studied measures of body composition and maximal aerobic capacity. 846 young men (25.5 ± 5.0 yrs) participated in the study. Maximal strength was measured using isometric bench press, leg extension and grip strength. Muscular endurance tests consisted of push-ups, sit-ups and repeated squats. An indirect graded cycle ergometer test was used to estimate maximal aerobic capacity (V(O2)max). Body composition was determined with bioelectrical impedance. Moreover, waist circumference (WC) and height were measured and body mass index (BMI) calculated. Maximal bench press was positively correlated with push-ups (r = 0.61, p < 0.001), grip strength (r = 0.34, p < 0.001) and sit-ups (r = 0.37, p < 0.001) while maximal leg extension force revealed only a weak positive correlation with repeated squats (r = 0.23, p < 0.001). However, moderate correlation between repeated squats and V(O2)max was found (r = 0.55, p < 0.001) In addition, BM and body fat correlated negatively with muscular endurance (r = -0.25 - -0.47, p < 0.001), while FFM and maximal isometric strength correlated positively (r = 0.36-0.44, p < 0.001). In conclusion, muscular endurance test scores were related to maximal aerobic capacity and body fat content, while fat free mass was associated with maximal strength test scores and thus is a major determinant for maximal strength. A contributive role of maximal strength to muscular endurance tests could be identified for the upper, but not the lower extremities. These findings suggest that push-up test is not only indicative of body fat content and maximal aerobic capacity but also maximal strength of upper body, whereas repeated squat test is mainly indicative of body fat content and maximal aerobic capacity, but not maximal strength of lower extremities.     

Arterial compliance of rowers: implications for combined aerobic and strength training on arterial elasticity

Regular endurance exercise increases central arterial compliance, whereas resistance training decreases it. It is not known how the vasculature adapts to a combination of endurance and resistance training. Rowing is unique, because its training encompasses endurance- and strength-training components. We used a cross-sectional study design to determine arterial compliance of 15 healthy, habitual rowers [50 +/- 9 (SD) yr, 11 men and 4 women] and 15 sedentary controls (52 +/- 8 yr, 10 men and 5 women). Rowers had been training 5.4 +/- 1.2 days/wk for 5.7 +/- 4.0 yr. The two groups were matched for age, body composition, blood pressure, and metabolic risk factors. Central arterial compliance (simultaneous ultrasound and applanation tonometry on the common carotid artery) was higher (P < 0.001) and carotid beta-stiffness index was lower (P < 0.001) in rowers than in sedentary controls. There were no group differences for measures of peripheral (femoral) arterial stiffness. The higher central arterial compliance in rowers was associated with a greater cardiovagal baroreflex sensitivity, as estimated during a Valsalva maneuver (r = 0.54, P < 0.005). In conclusion, regular rowing exercise in middle-aged and older adults is associated with a favorable effect on the elastic properties of the central arteries. Our results suggest that simultaneously performed endurance training may negate the stiffening effects of strength training.     

No apparent progress in bioelectrical impedance accuracy: validation against metabolic risk and DXA

Bioelectrical impedance (BIA) is quick, easy, and safe when quantifying fat and lean tissue. New BIA models (Tanita BC-418 MA, abbreviated BIA(8)) can perform segmental body composition analysis, e.g., estimate %trunkal fatness (%TF). It is not known, however, whether new BIA models can detect metabolic risk factors (MRFs) better than older models (Tanita TBF-300, abbreviated BIA(4)). We therefore tested the correlation between MRF and percentage whole-body fat (%BF) from BIA(4) and BIA(8) and compared these with the correlation between MRF and dual-energy X-ray absorptiometry (DXA, used as gold standard), BMI and waist circumference (WC). The sample consisted of 136 abdominally obese (WC >or= 88 cm), middle-aged (30-60 years) women. MRF included fasting blood glucose and insulin; high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides; high sensitive C-reactive protein, plasminogen activator inhibitor-1 (PAI-1), and fibrinogen; and alanine transaminase (ALT) liver enzyme. We found that similar to DXA, but in contrast to BMI, neither %BF BIA(4) nor %BF BIA(8) correlated with blood lipids or ALT. In the segmental analysis of %TF, BIA(8) only correlated with inflammatory markers, but not insulin, blood lipids, or ALT liver enzyme (in contrast to WC and %TF DXA). %TF DXA was associated with homeostatic model assessment insulin resistance (HOMA-IR) independently of WC (P = 0.03), whereas %TF BIA(8) was not (P = 0.53). Receiver-operating characteristic (ROC) curves confirmed that %TF BIA(8) did not differ from chance in the detection of insulin resistance (P = 0.26). BIA estimates of fatness were, at best, weakly correlated with obesity-related risk factors in abdominally obese women, even the new eight-electrode model. Our data support the continued use of WC and BMI.