Wayne Huey-Herng Sheu

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.

A relationship between serum ferritin and the insulin resistance syndrome is present in non‐diabetic women but not in non‐diabetic men

background Previous studies have suggested that serum ferritin is one of the components of the insulin resistance syndrome in Caucasians. Because serum ferritin levels differ significantly between men and women, variation in the role of ferritin in insulin resistance between the sexes, particularly in Asian populations, is still unknown.

Increased serum leptin concentrations correlate with soluble tumour necrosis factor receptor levels in patients with cirrhosis

Objective Several reports have documented the involvement of hyerleptinaemia in malnutrition associated with liver cirrhosis. However, the mechanisms of elevated leptin levels remains unclear. Serum concentrations of tumour necrosis factor‐α (TNF‐α), and two soluble TNF receptors (sTNF‐RI and sTNF–RII) are increased in patients with liver cirrhosis. In rodents, administration of TNF‐α has been shown to stimulate plasma leptin concentration, suggesting that a cytokine–leptin link may mediate anorexia and weight loss during chronic inflammation. In this study, we investigate the potential interaction of the TNF‐α system with leptin in the development of malnutrition in liver cirrhosis.

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.

Stimulated resistin expression in white adipose of rats with bile duct ligation-induced liver cirrhosis: relationship to cirrhotic hyperinsulinemia and increased tumor necrosis factor-alpha

Resistin, an adipose-derived polypeptide hormone, is proposed as a candidate of insulin resistance, although its roles in inhibiting adipogenesis and in inflammation have also been suggested. Liver cirrhosis is characterized by elevated circulating proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha), hyperinsulinemia and insulin resistance. The study aimed to examine resistin expression and its association with insulin and TNF-alpha in a cirrhotic rat model using bile duct ligation (BDL). The BDL-induced cirrhotic rats showed significantly lower fat mass, insulin sensitivity and elevated plasma insulin and TNF-alpha compared to sham animals. In addition, epididymal TNF-alpha and resistin mRNA and protein levels were higher in cirrhotic rats. In normal control rats, in vivo insulin infusion and ex vivo administration of TNF-alpha to cultured fat pads increased resistin gene expression significantly. These results implied that hyperinsulinemia and increased TNF-alpha levels might upregulate adipose resistin gene in BDL-induced liver cirrhosis. Further study is necessary to document the role of resistin in metabolic abnormalities of liver cirrhosis.

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.

Synergistic effect of renalase and chronic kidney disease on endothelin-1 in patients with coronary artery disease ‒ a cross-sectional study

Endothelin-1 (ET-1) is associated with endothelial dysfunction and vasoconstriction. Increased circulating ET-1 levels are associated with long-term cardiovascular mortality. Renalase, released from kidney, metabolizes catecholamines and regulates blood pressure. An increase in circulating renalase levels has been reported in patients with chronic kidney disease (CKD) and is associated with coronary artery disease (CAD). We hypothesized the existence of a synergistic effect of serum renalase levels and CKD on ET-1 levels in patients with CAD. We evaluated 342 non-diabetic patients with established CAD. ET-1 and renalase levels were measured in all patients after an overnight fast. Patients with CKD had higher ET-1 (1.95 ± 0.77 vs. 1.62 ± 0.76 pg/ml, P < 0.001) and renalase levels (46.8 ± 17.1 vs. 33.9 ± 9.9 ng/ml, P < 0.001) than patients without CKD. Patients with both CKD and high renalase levels (>the median of 36.2 ng/ml) exhibited the highest serum ET-1 (P value for the trend <0.001). According to multivariate linear regression analysis, the combination of high serum renalase levels with CKD was a significant risk factor for increased serum ET-1 levels (regression coefficient = 0.297, 95% confidence interval = 0.063‒0.531, P = 0.013). In conclusion, our data suggest a synergistic effect of high serum renalase levels and CKD on increases in ET-1 levels in patients with established CAD.

Association of MMP-9 to TIMP-1 ratio with long-term body weight and waist circumference after dietary weight reduction in men with metabolic syndrome.

N 21 Age, y 46 ± 11 Body weight, kg 94.4 ± 9.3 85.4 ± 10.8 b0.001 Body mass index, kg/m 32.7 ± 3.0 29.6 ± 3.7 b0.001 Waist circumference, cm 108.3 ± 8.0 97.2 ± 8.0 b0.001 Systolic blood pressure, mmHg 139 ± 17 120 ± 19 b0.001 Diastolic blood pressure, mmHg 79 ± 13 73 ± 12 0.018 Total cholesterol, mmol/l 5.3 ± 1.5 4.8 ± 0.9 0.024 HDL cholesterol, mmol/l 1.1 ± 0.2 1.1 ± 0.3 NS LDL cholesterol, mmol/l 3.2 ± 0.8 2.9 ± 0.7 0.035 Triglycerides, mmol/l 3.7 ± 6.6 2.2 ± 3.7 0.038 Fasting plasma glucose, mmol/l 5.8 ± 0.9 5.4 ± 0.6 0.01 Fasting serum insulin, pmol/l 102 ± 44 75 ± 36 0.001 HOMA-IR 4.4 ± 2.2 3.0 ± 1.6 0.002 Area of subcutaneous fat, cm 323 ± 85 235 ± 82 b0.001 Area of abdominal visceral fat, cm 488 ± 86 421 ± 81 b0.001 Leptin, ng/ml 14.1 ± 8.7 10.5 ± 9.9 NS Adiponectin, μg/ml 3.0 ± 1.7 3.1 ± 1.5 NS MMP-9, ng/ml 386 ± 144 387 ± 149 NS Dear Editor: