Metabolic syndrome, adiponectin and fat ROS

The metabolic syndrome, a cluster of insulin resistance, elevated blood pressure, and atherogenic dyslipidemia, is a common basis of atherosclerosis. Accumulation of intra-abdominal visceral fat stands upstream of the metabolic syndrome. Adipose tissue expresses a variety of genes for bioactive secretory proteins conceptualized as adipocytokines. We discovered a novel adipose-specific protein named adiponectin from human fat cDNAs. Adiponectin circulates in the plasma and its serum level is decreased in visceral fat accumulation. Results of experimental and clinical researches have demonstrated that hypoadiponectinemia underlies the pathogenesis of multiple diseases related to visceral fat accumulation, including atherosclerosis, hypertension, cardiac failure, insulin resistance, diabetes, hepatic steatosis, inflammatory bowel disease, and cancers. Recently, we revealed fat-derived reactive oxygen species (fat ROS) as an upstream factor in the development of hypoadiponectinemia and metabolic syndrome. Intervention targeting visceral fat accumulation, hypoadiponectinemia and fat ROS should be the way to therapeutically tackle the metabolic syndrome.Biomedical Reviews 2006; 17: 1-10

Hyperinsulinemia correlates with low levels of plasma B-type natriuretic peptide in Japanese men irrespective of fat distribution

<p>Abstract</p> <p>Background</p> <p>B-type natriuretic peptide (BNP), a member of the natriuretic peptide family, is a cardiac-derived secretory hormone with natriuretic, diuretic, and vasorelaxant activities. Intraabdominal fat accumulation is associated with atherosclerotic cardiovascular diseases and cardiac dysfunction. Circulating BNP levels are relatively low (within the normal limits) in obesity and the metabolic syndrome. However, the relationship between plasma BNP levels and visceral fat accumulation in general population has not been reported. The present study analyzed the relationships between plasma BNP levels and various clinical variables, including insulin, visceral and subcutaneous fat area (VFA and SFA, respectively), in normal Japanese men.</p> <p>Methods</p> <p>The study (Victor-J study) subjects were consecutive 500 Japanese male workers, who underwent a health checkup and were measured VFA and SFA by computed tomography.</p> <p>Results</p> <p>Age-adjusted simple linear regression analysis showed that log-BNP correlated positively with HDL-cholesterol, and negatively with VFA, log-immunoreactive insulin (IRI), log-triglyceride, and LDL-cholesterol, but not body mass index or SFA. Stepwise multiple regression analysis identified log-IRI and HDL-cholesterol as significant determinants of log-BNP. Subjects with IRI ≥5.5 μIU/mL had lower plasma BNP levels than those with IRI < 5.5 μIU/mL, irrespective of obesity (body mass index, cutoff value 25 kg/m²), visceral fat accumulation (VFA, cutoff value 100 cm²) and subcutaneous fat accumulation (SFA, cutoff value 128 cm²).</p> <p>Conclusions</p> <p>Our study showed that hyperinsulinemia correlated with low levels of plasma BNP in general men, irrespective of fat distribution.</p> <p>Trial registration</p> <p>UMIN 000004318.</p

Clinical significance of visceral fat reduction through health education in preventing atherosclerotic cardiovascular disease - Lesson from the Amagasaki Visceral Fat Study: A Japanese perspective

The metabolic syndrome has received worldwide recognition and is useful clinical aid in early-preventing atherosclerosis. Visceral adiposity is the main component of the metabolic syndrome in Japan, based on ethnic and racial difference in the pattern of adiposity. In the Amagasaki Visceral Fat Study, subjects had undergone annual health check-ups and then received health education by medical personnel. Visceral fat reduction improved hypoadiponectinemia and the number of obesity-related cardiovascular risk factors, and effectively prevented cardiovascular events. The health education that includes voluntary lifestyle modification aimed at reducing visceral fat could be useful in preventing cardiovascular events in the metabolic syndrome

Treatment-Induced Changes in Plasma Adiponectin Do Not Reduce Urinary Albumin Excretion in the Diabetes Prevention Program Cohort.

BACKGROUND AND OBJECTIVES: Molecular data suggests that adiponectin may directly regulate urinary albumin excretion. In the Diabetes Prevention Program (DPP) we measured adiponectin and albuminuria before and after intervention, and we previously reported increases in adiponectin with interventions. Here we have used the DPP dataset to test the hypothesis that treatment-related increases in adiponectin may reduce albuminuria in obesity. DESIGN, SETTING, PARTICIPANTS AND METHODS: We evaluated cross-sectional correlations between plasma adiponectin and urinary albumin excretion at baseline, and the relationship of treatment-related changes in adiponectin and albuminuria. Baseline and follow-up urine albumin to creatinine ratios (ACR (albumin to creatinine ratio)) and plasma adiponectin concentration were available in 2553 subjects. RESULTS: Adjusting for age, sex and race/ethnicity, we observed a statistically significant but weak inverse relationship between adiponectin and ACR at baseline (conditional Spearman\u27s rho = (-) 0.04, p = 0.04). Although DPP treatments significantly increased plasma adiponectin, there were no treatment effects on ACR and no differences in ACR across treatment groups. There was a weak direct (not inverse) association between change in adiponectin and change in albuminuria (adjusted Spearman\u27s rho = (+) 0.04, p = 0.03). CONCLUSIONS: In a large, well-characterized cohort of obese dysglycemic subjects we observed a weak inverse association between circulating adiponectin concentrations and urinary albumin excretion at baseline. Contrary to the hypothesized effect, treatment-related increases in plasma adiponectin were not associated with a reduction in ACR. The association of change in adiponectin with change in ACR should be assessed in populations with overt albuminuria before excluding a beneficial effect of increasing adiponectin to reduce ACR in obesity

Metabolic syndrome correlates intracoronary stenosis detected by multislice computed tomography in male subjects with sleep-disordered breathing

<p>Abstract</p> <p>Background</p> <p>Sleep-disordered breathing (SDB), especially obstructive sleep apnea (OSA), has frequent complications include hypertension, dyslipidemia and insulin resistance based on abdominal obesity or excess visceral fat (called Syndrome Z). OSA is a potential risk factor for cardiovascular diseases. The clinical characteristics of Japanese OSA subjects with OSA remain unclear. The present study investigated prevalence and predictive factors of intracoronary stenosis detected by multislice computed tomography (MSCT) in Japanese male subjects with SDB/OSA.</p> <p>Findings</p> <p>The study (O-VFStudy) subjects were 39 Japanese men with SDB/OSA who underwent all-night cardiorespiratory monitoring with fully attended polysomnography, and moreover both fat computed tomography (CT) scan and 64-row MSCT coronary angiography. The prevalence of coronary stenosis in this selected population with SDB/OSA was 15%. Logistic regression analysis showed a significant relationship between age-adjusted CAD and metabolic syndrome (<it>p </it>< 0.05), but not serum adiponectin levels and nocturnal fall in adiponectin. Subjects with the metabolic syndrome had significantly higher prevalence of CAD (31.3 versus 4.3%, <it>p </it>= 0.033), and lower levels of serum adiponectin (4.5 ± 0.6 versus 6.4 ± 0.6 μg/mL, <it>p </it>= 0.014), compared with groups without the metabolic syndrome.</p> <p>Conclusions</p> <p>The present study describes that the prevalence of greater than 50% intracoronary stenotic lesions detected by MSCT was 15% and the metabolic syndrome was correlated with intracoronary stenosis detected by MSCT in Japanese SDB/OSA subjects.</p> <p>Trial Registration</p> <p>UMIN 000002997</p> <p><url>https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000003633&language=E</url>.</p

Cross-sectional and longitudinal study of association between circulating thiobarbituric acid-reacting substance levels and clinicobiochemical parameters in 1,178 middle-aged Japanese men - the Amagasaki Visceral Fat Study

Abstract Background Circulating thiobarbituric acid-reacting substance (TBARS) levels, a marker of systemic oxidative stress, are predictive of cardiovascular events. However, they has not been evaluated in Japanese, especially with regard to the factors that contribute to the changes in circulating TBARS levels. We investigated the cross-sectional and longitudinal relationships between circulating TBARS levels and various clinicobiochemical parameters in middle-aged men. Methods In this population-based study (The Amagasaki Visceral Fat Study), 1,178 Japanese male urban workers who had undergone health check-ups in 2006, 2007 and 2008 and were not on medications for metabolic disorders during the follow-up period, were enrolled. Serum TBARS levels were measured by the method of Yagi. The estimated visceral fat area (eVFA) by bioelectrical impedance was measured annually. After health check-ups, subjects received health education with lifestyle modification by medical personnel. Results The number of cardiovascular risk factors (hypertension, hyperglycemia, low HDL-C, hypertriglyceridemia, hyperuricemia, hyper-LDL-C and impaired renal function) augmented with the increases in log-eVFA (p &lt; 0.0001) and log-TBARS (p &lt; 0.0001). The combination of TBARS and eVFA had a multiplicative effect on risk factor accumulation (F value = 79.1, p = 0.0065). Stepwise multiple regression analysis identified log-eVFA, as well as age, log-body mass index (BMI), LDL-C, log-adiponectin, γ-glutamyl transpeptidase (γ-GTP) and uric acid as significant determinants of log-TBARS. Stepwise multiple regression analysis identified one-year changes in eVFA as well as BMI, γ-GTP and estimated glomerular filtration rate (eGFR) as significant determinants of one-year change in TBARS, and biennial changes in eVFA as well as BMI and γ-GTP, eGFR as significant determinants of biennial change in TBARS. Conclusions The present study showed a significant cross-sectional and longitudinal correlation between TBARS and eVFA, as well as BMI and γ- GTP, eGFR. Visceral fat reduction may independently associate with the improvement in systemic ROS in middle-aged Japanese men. Trial Registration The Amagasaki Visceral Fat Study UMIN000002391. </jats:sec

Amphotericin B assembles into seven-molecule ion channels: An NMR and molecular dynamics study

Amphotericin B, an antifungal drug with a long history of use, forms fungicidal ion-permeable channels across cell membranes. Using solid-state nuclear magnetic resonance spectroscopy and molecular dynamics simulations, we experimentally elucidated the three-dimensional structure of the molecular assemblies formed by this drug in membranes in the presence of the fungal sterol ergosterol. A stable assembly consisting of seven drug molecules was observed to form an ion conductive channel. The structure is somewhat similar to the upper half of the barrel-stave model proposed in the 1970s but substantially different in the number of molecules and in their arrangement. The present structure explains many previous findings, including structure-activity relationships of the drug, which will be useful for improving drug efficacy and reducing adverse effects

Correlation of insulin resistance and motor function in spinal and bulbar muscular atrophy

This study aimed to evaluate various metabolic parameters in patients with spinal and bulbar muscular atrophy (SBMA), to investigate the association between those indices and disease severity, and to explore the underlying molecular pathogenesis. We compared the degree of obesity, metabolic parameters, and blood pressure in 55 genetically confirmed SBMA patients against those in 483 age- and sex-matched healthy control. In SBMA patients, we investigated the correlation between these factors and motor functional indices. SBMA patients had lower body mass index, blood glucose, and Hemoglobin A1c, but higher blood pressure, homeostasis model assessment of insulin resistance (HOMA-IR, a marker of insulin resistance), total cholesterol, and adiponectin levels than the control subjects. There were no differences in visceral fat areas, high-density lipoprotein-cholesterol (HDL-C), or triglyceride levels in two groups. Revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R) correlated positively with HDL-C, but negatively with HOMA-IR. Through stepwise multiple regression analysis, we identified HOMA-IR as a significant metabolic determinant of ALSFRS-R. In biochemical analysis, we found that decreased expressions of insulin receptors, insulin receptor substrate-1 and insulin receptor-β, in autopsied muscles and fibroblasts of SBMA patients. This study demonstrates that SBMA patients have insulin resistance, which is associated with the disease severity. The expressions of insulin receptors are attenuated in the skeletal muscle of SBMA, providing a possible pathomechanism of metabolic alterations. These findings suggested that insulin resistance is a metabolic index reflecting disease severity and pathogenesis as well as a potential therapeutic target for SBMA.journal articl