Young Sook Song

Effects of weight reduction on serum vaspin concentrations in obese subjects: modification by insulin resistance.

Visceral adipose tissue‐derived serpin (vaspin) has been regarded as a novel adipokine with potential insulin sensitizing properties. We investigated the changes of serum vaspin concentration in response to weight reduction, and the associations between changes in serum vaspin concentrations and changes of anthropometric and metabolic variables in obese subjects after weight reduction. We performed a longitudinal clinical intervention study on 63 obese persons enrolled in a 12‐week weight reduction program that included lifestyle modification and adjuvant treatment with the antiobesity agent orlistat. Anthropometric variables, lipid profiles, fasting glucose, fasting insulin, and serum vaspin concentrations were measured. Statistical analyses were performed according to the homeostasis model assessment of insulin resistance (HOMAIR). Serum vaspin concentrations decreased significantly in responders (≥2% reduction in baseline weight), but not in nonresponders (<2% reduction in baseline weight). Changes in serum vaspin concentrations were significantly correlated with body weight, BMI, waist circumference, and hip circumference in the higher, but not in the lower, HOMAIR group. In multivariate linear regression analysis, change in serum vaspin concentrations in the higher, but not in the lower, HOMAIR group was positively correlated with change in BMI and negatively correlated with initial HOMAIR level. The associations between changes in serum vaspin concentrations and changes in anthropometric and metabolic parameters differed according to insulin resistance status in obese subjects. These relationships were more prominent in the higher HOMAIR group. Insulin resistance may influence the correlations between changes in serum vaspin concentration and related metabolic variables.

Association between low SIRT1 expression in visceral and subcutaneous adipose tissues and metabolic abnormalities in women with obesity and type 2 diabetes

AIMS To assess the importance of adipose tissue sirtuin 1 (SIRT1) in the regulation of whole-body metabolism in humans with obesity and type 2 diabetes. METHODS In total, 19 non-diabetic obese women, 19 type 2 diabetic women undergoing gastric bypass surgery, and 27 normal-weight women undergoing gynecological surgery (total 65 women) were enrolled. Their anthropometric variables, abdominal fat distribution and metabolic parameters, serum adiponectin concentrations, and SIRT1 mRNA and protein and adiponectin mRNA expressions in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were measured. RESULTS SIRT1 mRNA levels in VAT and SAT were similar and these levels were suppressed in obese and type 2 diabetic women compared to normal-weight subjects. These decreases in SIRT1 expression were observed in both adipocytes and non-fat cells. There was a strong association between adipose tissue SIRT1 mRNA and protein levels. Adipose SIRT1 expression correlated inversely with HOMA-IR and other insulin resistance-related parameters. Adipose SIRT1 and adiponectin mRNA expression correlated very strongly and positively. SIRT1 mRNA level in VAT correlated inversely with visceral obesity whereas its expression in SAT correlated negatively with body mass index. CONCLUSIONS Adipose tissue SIRT1 may play a key role in the regulation of whole body metabolic homeostasis in humans. Downregulation of SIRT1 in VAT may contribute to the metabolic abnormalities that are associated with visceral obesity.

IL-34 is associated with obesity, chronic inflammation, and insulin resistance.

OBJECTIVES IL-34 is a recently identified alternative ligand for colony-stimulating factor-1 (CSF-1) receptor. IL-34 and CSF-1 are regulators of differentiation, proliferation, and survival in mononuclear phagocytes. Here, we investigated the IL-34 serum concentration and expression in human adipose tissues and any associations with insulin resistance. METHODS We recruited 19 nondiabetic obese women, 9 type 2 diabetic women, and 27 normal-weight women. Metabolic parameters, abdominal fat distribution, serum IL-34 concentration, and IL-34 mRNA expression were measured in abdominal sc adipose tissue (SAT) and visceral adipose tissue (VAT). In addition, the expression/secretion and putative effects of IL-34 were assessed in human differentiated adipocytes. Serum IL-34 concentration was measured before and 5 to 9 months after laparoscopic Roux-en-Y gastric bypass surgery was performed on the 20 obese patients. RESULTS Regardless of diabetes status, obese patients demonstrated significantly higher serum IL-34 concentrations than controls. Serum IL-34 was significantly and positively correlated with insulin resistance-related metabolic parameters. IL-34 mRNA was significantly higher in VAT than SAT. IL-34 was expressed in adipocytes as well as nonadipocytes, and expression was significantly higher during adipogenesis. In differentiated adipocytes, the expression/secretion of IL-34 was enhanced by TNFα and IL-1β. In addition, IL-34 augmented fat accumulation and inhibited the stimulatory effects of insulin on glucose transport. Moreover, serum IL-34 was significantly decreased after Roux-en-Y gastric bypass-induced weight loss. CONCLUSION The present study demonstrates, for the first time, that IL-34 is expressed in human adipose tissues and the circulating concentration is significantly elevated in obese patients. This suggests that IL-34 is associated with insulin resistance.

Implication of phosphorylation of the myosin II regulatory light chain in insulin-stimulated GLUT4 translocation in 3T3-F442A adipocytes.

In adipocytes, insulin stimulates glucose transport primarily by promoting the translocation of GLUT4 to the plasma membrane. Requirements for Ca2+/ calmodulin during insulin-stimulated GLUT4 translocation have been demonstrated; however, the mechanism of action of Ca2+ in this process is unknown. Recently, myosin II, whose function in non-muscle cells is primarily regulated by phosphorylation of its regulatory light chain by the Ca2+/calmodulin-dependent myosin light chain kinase (MLCK), was implicated in insulin-stimulated GLUT4 translocation. The present studies in 3T3- F442A adipocytes demonstrate the novel finding that insulin significantly increases phosphorylation of the myosin II RLC in a Ca2+-dependent manner. In addition, ML-7, a selective inhibitor of MLCK, as well as inhibitors of myosin II, such as blebbistatin and 2,3-butanedione monoxime, block insulin- stimulated GLUT4 translocation and subsequent glucose transport. Our studies suggest that MLCK may be a regulatory target of Ca2+/calmodulin and may play an important role in insulin-stimulated glucose transport in adipocytes.

Association between serum vaspin concentrations and visceral adipose tissue in Korean subjects.

Adipokines modulate multiple signaling pathways of insulin resistance via endocrine, paracrine, or autocrine mechanisms. Visceral adipose tissue (VAT)-derived serpin (vaspin) is a novel adipokine with potential insulin-sensitizing effects. We investigated the association between serum vaspin concentrations and abdominal adiposity. We recruited subjects (N = 150) aged 20 to 69 years who visited our hospital for regular health examinations. Abdominal VAT and subcutaneous adipose tissue areas were assessed by computed tomography. We measured serum vaspin concentrations by enzyme-linked immunosorbent assay. Statistical analysis was performed after stratification, using a homeostasis model for insulin resistance (HOMA-IR). Serum vaspin concentrations correlated positively with age (r = 0.196) when data from all subjects were analyzed. In the higher-HOMA-IR group, serum vaspin levels correlated more prominently with age (r = .344) and VAT area (r = .327) although these associations were not found in the lower-HOMA-IR group. In multivariate linear regression analysis, the VAT area was independently correlated with serum vaspin concentrations in the higher-HOMA-IR group. The association between serum vaspin concentrations and VAT differs according to insulin resistance. Insulin resistance might influence the correlation between serum vaspin concentration and VAT in human subjects.

Clinical and Radiogical Outcomes of Endovascular Detachable Coil Embolization in Paraclinoid Aneurysms : A 10-Year Experience

OBJECTIVE Direct surgical clipping of paraclinoid aneurysms poses technical challenges to even very experienced neurosurgeons, making endovascular treatment an alternative treatment modality in many centers. We have therefore retrospectively evaluated the safety and efficacy of endovascular detachable coil embolization of paraclinoid aneurysms. METHODS From June 1997 to June 2007, 65 patients underwent endovascular detachable coiling for 67 paraclinoid aneurysms (of which 9 were ruptured and 58 were unruptured) in our institute. Their medical records, radiological images and readings, and operation records were reviewed retrospectively. RESULTS After the initial embolization procedure, complete occlusion was achieved in 29 (43.3%) of the aneurysms treated by endovascular detachable coiling. Six aneurysms required retreatment, with two each requiring one, two, or three additional endovascular procedures. Fifty-five (82.1%) aneurysms were measured by three-dimensional time of flight (TOF) magnetic resonance images (MRI) or transfemoral cerebral angiography (TFCA) at a mean follow-up of 29.7 months (range from 4 to 94 months), with 39 aneurysms (70.9%) showing complete occlusion. Thromboembolic events (3.8%) were the most frequent complication. Rupture did not occur during or after any of the procedures. According to the Glasgow Outcome Scale (GOS), 98.4% of the patients treated by coil embolization had a score of 4 or 5. CONCLUSION Our results indicate that endovascular detachable coiling is a safe and effective treatment modality in paraclinoid aneurysms.

Fibronectin Gene Expression in Human Adipose Tissue and Its Associations with Obesity-Related Genes and Metabolic Parameters

BackgroundLimited data are available on the in vivo expression of fibronectin, one of the main extracellular matrix components. We investigated the expression of fibronectin in abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) and the associations of leptin, adiponectin, and vaspin gene expression with metabolic parameters in obese women.MethodsWe recruited female subjects undergoing bariatric surgery for obesity (n = 24) and patients undergoing benign gynecological surgery as the control group (n = 23). We measured anthropometric variables, abdominal fat distribution, metabolic parameters, serum concentrations of leptin, adiponectin, and vaspin, and depot-specific mRNA expression of fibronectin, leptin, adiponectin, and vaspin.ResultsFibronectin expression in both VAT and SAT was significantly lower in the obese group than in the control group. Fibronectin expression in both VAT and SAT were negatively correlated with body mass index or waist circumference, with higher prominence in VAT. In multiple regression analysis, fibronectin expression in both VAT and SAT was negatively correlated with serum leptin concentration. Fibronectin expression in VAT was negatively correlated with leptin expression in VAT. Additionally, fibronectin expression in SAT was negatively correlated with leptin expression in SAT and positively correlated with adiponectin expression in VAT and SAT.ConclusionsWe found significant negative associations between depot-specific fibronectin expression in human adipose tissue and obesity indices and obesity-related biomarkers. Our results suggest that fibronectin expression may contribute to obesity and metabolic dysregulation in humans.

Multimodal treatment for complex intracranial aneurysms: clinical research.

OBJECTIVE For patients with giant or dissecting aneurysm, multimodal treatment consisting extracranial-intracranial bypass surgery plus clip or coil for parent artery occlusion may be necessary. In this study, the safety and efficacy of multimodal treatment in 15 patients with complex aneurysms were evaluated retrospectively. METHODS From January 1995 to June 2007, the authors treated 15 complex aneurysms that were unable to be clipped or coiled. Among them, nine patitents had unruptured aneurysms and 6 had ruptured aneurysms. Aneurysms were located in the internal cerebral artery (ICA) in 11 patients (4 in the dorsal wall, 4 in the terminal ICA, 1 in the paraclinoid, and 2 in the cavernous ICA), in the middle cerebral artery (MCA) in 2, and in the posterior circulation in two patients RESULTS Fifteen patients with complex aneurysms were treated with bypass surgery previously. Thirteen patients were treated with external carotid middle cerebral artery (ECA-MCA) anastomosis, and one patient with superficial temporal to posterior cerebral artery (STA-PCA) and another patient with occipital artery to posterior inferior cerebellar artery (OA-PICA) anastomosis. Parent artery occlusion was then performed with a clip in 9 patients, with a coil in 4, with balloon plus coil in one patient. All 15 aneurysms were successfully treated with clip or coil combined with bypass surgery. Follow-up angiograms showed good patency of anastomotic site in 10 out of 11 patients, and perfusion study showed sufficient perfusion in 6 out of 9 patients. CONCLUSION These findings indicate that for patients with complex aneurysms, clip or coil for parent vessel occlusion with additive bypass surgery can successfully exclude the aneurysm from the neurovascular circulatory system.