Ya-Yu Wang

Association between adenomas of rectosigmoid colon and metabolic syndrome features in a Chinese population

Background and Aims:  Metabolic syndrome (MS) consists of a cluster of diseases, including obesity, dyslipidemia, hyperglycemia and high blood pressure. The purpose of the present study was to assess the association of MS with adenomas of the rectosigmoid colon, a well‐established precancerous lesion.

Adipose proinflammatory cytokine expression through sympathetic system is associated with hyperglycemia and insulin resistance in a rat ischemic stroke model

Patients who experience acute ischemic stroke may develop hyperglycemia, even in the absence of diabetes, but the exact mechanisms are still unclear. Adipose tissue secretes numerous proinflammatory cytokines and is involved in the regulation of glucose metabolism. This study aimed to determine the effects of acute stroke on adipose inflammatory cytokine expression. In addition, because sympathetic activity is activated after acute stroke and catecholamines can regulate the expression of several adipocytokines, this study also evaluated whether alterations in adipose proinflammatory cytokines following acute stroke, if any, were medicated by sympathetic system. Acute ischemic brain injury was induced by ligating the right middle cerebral artery and bilateral common carotid arteries in male adult Sprague-Dawley rats. Adipose tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) mRNA and protein levels were determined by RT-PCR and enzyme-linked immunoassay, respectively. The stroke rats developed glucose intolerance on days 1 and 2 after cerebral ischemic injury. The fasting blood insulin levels and insulin resistance index measured by homeostasis model assessment were higher in the stroke rats compared with the sham group. Epididymal adipose TNF-α and MCP-1 mRNA and protein levels were elevated one- to twofold, in association with increased macrophage infiltration into the adipose tissue. When the rats were treated with a nonselective β-adrenergic receptor blocker, propranolol, before induction of cerebral ischemic injury, the acute stroke-induced increase in TNF-α and MCP-1 was blocked, and fasting blood insulin concentration and homeostasis model assessment-insulin resistance were decreased. These results suggest a potential role of adipose proinflammatory cytokines induced by the sympathetic nervous system in the pathogenesis of glucose metabolic disorder in rats with acute ischemic stroke.

Activation of Hepatic Inflammatory Pathways by Catecholamines Is Associated With Hepatic Insulin Resistance in Male Ischemic Stroke Rats

Patients who experience acute ischemic stroke may develop hyperglycemia, even in the absence of diabetes. In the current study we determined the effects of acute stroke on hepatic insulin signaling, TNF-α expression, endoplasmic reticulum (ER) stress, the activities of c-Jun N-terminal kinase (JNK), inhibitor κB kinase β (IKK-β), and nuclear factor-κB (NF-κB) pathways. Rats with cerebral ischemia developed higher blood glucose, and insulin levels, and insulin resistance index, as well as hepatic gluconeogenic enzyme expression compared with the sham-treated group. The hepatic TNF-α mRNA and protein levels were elevated in stroke rats in association with increased ER stress, phosphorylation of JNK1/2 and IKK-β proteins, IκB/NF-κB signaling, and phosphorylation of insulin receptor-1 (IRS-1) at serine residue. The basal and insulin-stimulated tyrosine phosphorylation of IRS-1 and AKT proteins was reduced. In addition, acute stroke increased circulating catecholamines in association with hepatic adrenergic signaling activation. After administration of a nonselective β-adrenergic receptor blocker (propranolol) before induction of cerebral ischemic injury, hepatic adrenergic transduction, TNF-α expression, ER stress, and the activation of the JNK1/2, IKK-β, and NF-κB pathways, and serine phosphorylation of IRS-1 were all attenuated. In contrast, the phosphorylated IRS-1 at tyrosine site and AKT levels were partially restored with improved poststroke hyperglycemia and insulin resistance index. These results suggest that acute ischemic stroke can activate proinflammatory pathways in the liver by the catecholamines and is associated with the development of hepatic insulin resistance.

Hyperglycemia is associated with enhanced gluconeogenesis in a rat model of permanent cerebral ischemia

Hyperglycemia is common after acute stroke. In the acute phase of stroke (within 24h), rats with permanent cerebral ischemia developed higher fasting blood glucose and insulin levels in association with up-regulation of hepatic gluconeogenic gene expression, including phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, and fructose-1,6-bisphosphatase. In addition, hepatic gluconeogenesis-associated positive regulators, such as FoxO1, CAATT/enhancer-binding proteins (C/EBPs), and cAMP responsive element-binding protein (CREB), were up-regulated. For insulin signaling transduction, phosphorylation of insulin receptor (IR), insulin receptor substrate-1 (IRS1) at the tyrosine residue, Akt, and AMP-activated protein kinase (AMPK), were attenuated in the liver, while negative regulators of insulin action, including phosphorylation of p38, c-Jun N-terminal kinase (JNK), and insulin receptor substrate-1 (IRS1) at the serine residue, were increased. In addition, the brains of rats with stroke exhibited a reduction in phosphorylation of IRS1 at the tyrosine residue and Akt. Circulating cortisol, glucagon, C-reactive protein (CRP), monocyte chemoattractant protein 1 (MCP-1), and resistin levels were elevated, but adiponectin was reduced. Our data suggest that cerebral ischemic insults might modify intracellular and extracellular environments, favoring hepatic gluconeogenesis and the consequences of hyperglycemia.

Obesity and diabetic hyperglycemia were associated with serum alanine aminotransferase activity in patients with hepatitis B infection.

Several studies have reported that obesity and diabetes are important risk factors for elevated blood aminotransferase activity in individuals with no underlying causes of liver disease. The aim of this study was to determine whether obesity and fasting glucose level were associated with hepatic dysfunction in patients with hepatitis B infection. A total of 934 patients with hepatitis B infection were enrolled, among whom increased alanine aminotransferase (ALT) activity (> or =40 IU/L) was observed in 25.1%. By univariate analysis, factors associated with increased ALT activity among patients with hepatitis B infection included body mass index (BMI), fasting blood glucose level, and blood triglyceride and high-density cholesterol levels. By multivariate logistic regression analysis, BMI and fasting blood glucose level were independent predictors of elevated ALT activity, with odds ratios of 1.73 (95% confidence interval, 1.17-2.56) for subjects with a BMI greater than or equal to 25 kg/m2 and 1.88 (95% confidence interval, 1.06-3.33) for subjects with a fasting blood glucose greater than or equal to 126 mg/dL. Even in subjects with ALT activity within the reference range, ALT activity was found to be associated with BMI. In conclusion, a BMI greater than or equal to 25 kg/m2 and a fasting blood glucose level greater than or equal to 126 mg/dL were risk factors for increased ALT activity in subjects with hepatitis B infection, suggesting that obesity and diabetic fasting hyperglycemia may aggravate liver injury in this population.

Protein nitration is associated with increased proteolysis in skeletal muscle of bile duct ligation–induced cirrhotic rats

Cirrhosis is characterized by skeletal muscle wasting. In this study, the effects of nitric oxide production on skeletal muscle protein nitration and degradation in cirrhosis were investigated. Cirrhosis was induced by bile duct ligation (BDL) in Sprague-Dawley rats for 4 weeks. The BDL-induced cirrhotic rats and sham-operated rats were then injected daily with either saline or N(G)-l-nitro-arginine methyl ester (l-NAME) for 7 days from week 4 to week 5, after which nitrite/nitrate, glutathione reduction, as well as protein nitration, ubiquitination, and degradation were assessed in skeletal muscle. Elevated muscular nitrite/nitrate concentrations, protein nitration, total ubiquitin conjugates, and degradation fragments of myosin heavy chain as well as diminished glutathione reduction levels were observed in BDL-induced cirrhotic rats as compared with controls. Administration of l-NAME for 1 week led to reduction of nitrite/nitrate levels; protein nitration was also decreased in the skeletal muscle. In addition, ubiquitination of muscular proteins and degradation of myosin heavy chain were significantly diminished after treatment of l-NAME. In conclusion, nitrosative stress occurred in the skeletal muscle of BDL-induced cirrhotic rats and may lead to increased proteolysis of muscle-specific structural proteins.

Serum total bilirubin concentrations are inversely associated with total white blood cell counts in an adult population

Background Several studies have shown that serum bilirubin has a protective effect against cardiovascular disease and that inflammation plays an important role in its pathogenesis. This cross-sectional study investigated whether there was an association between blood total white blood cell count, a simple indicator of inflammation, and serum total bilirubin concentration in a cohort of an adult population in Taiwan. Methods A total of 2458 apparently healthy adults (1246 men and 1212 women) who attended health examination at a medical centre in central Taiwan were enrolled. We collected anthropometric measurements, fasting blood test results, lifestyle habits and medical history. Results Total white blood cell counts decreased progressively when the concentrations of total bilirubin increased as demonstrated in the total bilirubin quartiles. Both total bilirubin concentrations and total white blood cell counts showed significant correlations with the components of metabolic syndrome, including triglyceride and high-density lipoprotein cholesterol concentrations. Multivariate linear regression analysis revealed that, for both genders, total bilirubin showed an independent negative correlation with total white blood cell count after adjusting for conventional cardiovascular risk factors. Conclusions Higher serum total bilirubin concentrations within the reference range were associated with lower blood total white blood cell counts, regardless of other classical cardiovascular risk factors.

Skeletal muscle proteolysis is associated with sympathetic activation and TNF-α-ubiquitin-proteasome pathway in liver cirrhotic rats.

This study examined the effects of adrenergic blockade on muscle wasting and expression of the ubiquitin‐proteasome system, tumor necrosis factor‐α (TNF‐α) and its signaling pathways in skeletal muscles of cirrhotic rats.

Age and sex differences in the relationship between neutrophil-to-lymphocyte ratio and chronic kidney disease among an adult population in Taiwan

BACKGROUND This study investigated the association between systemic inflammation and chronic kidney disease (CKD), and whether this association changes with aging in adults, by using neutrophil-to-lymphocyte ratio (NLR) as an inflammation marker. MATERIALS AND METHODS A total of 2954 adults (1815 men and 1139 women) who attended a health examination at a medical center in central Taiwan were included for the final cross-sectional analysis. RESULTS Compared with participants aged <60 years, participants aged ≥60 years had a markedly higher prevalence rate of CKD in both men (7.6% vs. 37.8%, p < .001) and women (3.8% vs. 28.0%, p < .001). In men aged <60 years, multivariable logistic regression analysis revealed that, after adjusting for conventional CKD risk factors, higher NLR (per 1 unit increment) was independently associated with higher risk of CKD [adjusted OR = 1.48 (95% C.I.: 1.10 to 1.99, p = .009)]. There was no such association in both men and women aged ≧60 years, and woman aged <60 years. CONCLUSIONS Our study showed a differential effect that aging has on the relationship between NLR and CKD in men but not in women. Being inexpensive and readily available, NLR may potentially be used for CKD risk assessment in men younger than 60 years of age.