benzofurans and Metabolic-Syndrome

Background exposure to persistent organic pollutants (POPs) has emerged as a new risk factor for metabolic syndrome (MetS), while hyperuricemia is associated with MetS through unclear mechanisms.. We examined cross-sectional data for consistency with the hypothesis that POPs are a common underlying risk factor of both MetS and hyperuricemia.. We evaluated associations of POPs with hyperuricemia in subjects aged ≥20 years in the population-based National Health and Nutrition Examination Survey (NHANES) 2003-2004. Sample size was n = 1331 for organochlorine (OC) pesticides and n = 1299 for polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs).. Among all subjects, the risk of hyperuricemia was higher for higher serum concentrations of OC pesticides, PCDDs, and dioxin-like PCBs. PCDFs and nondioxin-like PCBs did not show any clear trend. Adjusted odds ratios (ORs) for OC pesticides, PCDDs, and dioxin-like PCBs were 1.0, 2.4, 2.3, 3.0, and 2.5 (P trend = 0.05), 1.0, 1.6, 1.4, 2.1, and 2.5 (P trend = 0.01), and 1.0, 1.3, 1.4, 1.3, and 2.4 (P trend = 0.04). When we restricted the analyses to subjects without MetS, all these associations appeared to strengthen.. This study is consistent with our hypothesis that the risk of hyperuricemia relates to background exposure to a mixture of POPs even among persons without MetS. There should be further research about whether avoiding exposure to POPs and otherwise decreasing body burden of POPs would be helpful to prevent or manage hyperuricemia or gout.

Topics: Adult; Aged; Aged, 80 and over; Benzofurans; Chlorine; Cross-Sectional Studies; Dibenzofurans, Polychlorinated; Dioxins; Environmental Pollutants; Female; Humans; Hyperuricemia; Male; Metabolic Syndrome; Middle Aged; Nutrition Surveys; Odds Ratio; Organic Chemicals; Pesticides; Polychlorinated Biphenyls; Polychlorinated Dibenzodioxins; Risk Factors; United States; Young Adult

The inhibition of protein tyrosine phosphatase 1B (PTP1B) is considered a valid strategy to combat insulin resistance and type II diabetes. We show here that a dichloromethane extract of Ratanhiae radix ( RR_EX) dose-dependently inhibits human recombinant PTP1B in vitro and enhances insulin-stimulated glucose uptake in murine myocytes. By determination of the PTP1B inhibiting potential of 11 recently isolated lignan derivatives from RR_EX, the observed activity of the extract could be partly assigned to ratanhiaphenol III. This compound inhibited PTP1B in vitro with an IC (50) of 20.2 µM and dose-dependently increased insulin receptor phosphorylation as well as insulin-stimulated glucose uptake in cultured myotubes. This is the first report to reveal an antidiabetic potential for a constituent of rhatany root, traditionally used against inflammatory disorders, by showing its capability of inhibiting PTP1B.

Topics: Animals; Benzofurans; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Enzyme Inhibitors; Glucose; Humans; Hypoglycemic Agents; Insulin Resistance; Krameriaceae; Lignans; Metabolic Syndrome; Mice; Muscle Cells; Muscle Fibers, Skeletal; Phytotherapy; Plant Preparations; Plant Roots; Protein Tyrosine Phosphatase, Non-Receptor Type 1

Metabolic syndrome (MetS) consists of a constellation of metabolic abnormalities that confer increased risk of cardiovascular disease. There is a positive correlation between exposure to persistent organic pollutants and MetS. We examine the association between PCDD/Fs and MetS components in 1490 non-diabetic persons living near a highly dioxin-contaminated area. We used factor analysis, with a set of core variables considered central features of MetS and PCDD/Fs, to group similar risk factors. Serum PCDD/Fs were positively and significantly correlated with the number of MetS components. Four risk factors-lipidemia, blood pressure, body size, and glycemia-accounted for 72.6% of the variance in the 10 core factors, and PCDD/Fs were linked to MetS through shared correlations with high blood pressure. After adjusting for confounding factors, we found that diastolic blood pressure (β=0.018; p=0.006), glucose (β=0.013; p=0.046), and waist circumference (β=0.721; p=0.042) significantly increased with increasing serum PCDD/F levels. We found significant trends for associations between metabolic syndrome and serum low-chlorinated PCDD/Fs. The highest quintiles of 2,3,4,7,8-PeCDF, 1,2,3,6,7,8-HxCDF and 2,3,7,8-TCDD had the top three adjusted ORs (95% CI) of 3.5 (1.9-6.3), 2.9 (1.7-4.9) and 2.8 (1.6-4.9), respectively. We also found a slight monotonic relationship between serum PCDD/Fs and the prevalence of MetS, especially when the serum dioxin level was higher than 25.4pg WHO(98)-TEQ(DF)g(-1) lipid (the fourth Quintile). We hypothesize that high-dose exposure to PCDD/Fs is a blood pressure-related factor that raises MetS risk.

Topics: Adult; Aged; Benzofurans; Dibenzofurans, Polychlorinated; Environmental Exposure; Environmental Pollutants; Female; Humans; Hypertension; Male; Metabolic Syndrome; Middle Aged; Polychlorinated Dibenzodioxins; Taiwan

Environmental exposure to some persistent organic pollutants has been reported to be associated with a metabolic syndrome in the U.S. population.. We evaluated the associations of body burden levels of dioxins and related compounds with the prevalence of metabolic syndrome among the general population in Japan.. We conducted a cross-sectional study with 1,374 participants not occupationally exposed to these pollutants, living throughout Japan during 2002-2006. In fasting blood samples, we measured biochemical factors and determined lipid-adjusted concentrations of 10 polychlorinated dibenzo-p-dioxins (PCDDs), 7 polychlorinated dibenzofurans (PCDFs), and 12 dioxin-like poly-chlorinated biphenyls (DL-PCBs) all of which have toxic equivalency factors. We also performed a questionnaire survey.. The toxic equivalents (TEQs) of PCDDs, PCDFs, and DL-PCBs and total TEQs had significant adjusted associations with metabolic syndrome, whether or not we excluded diabetic subjects. By analyzing each component of metabolic syndrome separately, the DL-PCB TEQs and total TEQs were associated with all components, and the odds ratios (ORs) in the highest quartile of DL-PCB TEQs in four of the five components were higher than those for PCDDs or PCDFs. We also found congener-specific associations with metabolic syndrome; in particular, the highest quartiles of PCB-126 and PCB-105 had adjusted ORs of 9.1 and 7.3, respectively.. These results suggest that body burden levels of dioxins and related compounds, particularly those of DL-PCBs, are associated with metabolic syndrome. Of the components, high blood pressure, elevated triglycerides, and glucose intolerance were most closely associated with these pollutants.

Topics: Adolescent; Adult; Aged; Benzofurans; Body Burden; Dibenzofurans, Polychlorinated; Environmental Pollutants; Female; Humans; Japan; Male; Metabolic Syndrome; Middle Aged; Polychlorinated Biphenyls; Polychlorinated Dibenzodioxins; Prevalence; Young Adult

Hypertension is commonly accompanied by obesity, hyperlipidemia, and insulin resistance in humans, a cluster of abnormalities known as metabolic syndrome X. With the notable exception of inhibitors of the renin-angiotensin system, which have mildly beneficial effects on insulin resistance, most antihypertensive agents worsen one or more components of metabolic syndrome X. Second-generation centrally acting antihypertensive agents such as rilmenidine and moxonidine have mixed effects on components of metabolic syndrome X, which might reflect in part actions on two different receptors: I(1)-imidazoline and alpha(2)-adrenergic. Using a rat model of metabolic syndrome X, we sought to separate the influence of these two receptors on glucose and lipid metabolism by using selective antagonists. Rilmenidine and moxonidine acutely raised glucose and lowered insulin, thereby further worsening glucose tolerance. These effects were entirely mediated by alpha(2)-adrenergic receptors. Rilmenidine and moxonidine also lowered glucagon, an effect that was mediated solely by I(1)-imidazoline receptors since it was potentiated by alpha(2)-blockade, but eliminated in the presence of I(1)-antagonists. Lowering of triglyceride and cholesterol levels followed the same pattern as glucagon, implicating I(1)-imidazoline receptors in lipid-lowering actions. Chronic treatment with moxonidine reproduced the beneficial effects on glucagon and lipids while the acute hyperglycemic response did not persist. Thus, alpha(2)-adrenergic receptors mediate an acute deterioration of glucose tolerance, whereas in contrast I(1)-imidazoline receptors appear to mediate the persistent long-term improvements in glucose tolerance. The therapeutic action of I(1)-imidazoline agonists may be primarily mediated through reduced glucagon secretion.

Topics: Adrenergic alpha-Antagonists; Animals; Antihypertensive Agents; Benzofurans; Blood Pressure; Disease Models, Animal; Female; Glucagon; Glucose; Glucose Tolerance Test; Humans; Imidazoles; Imidazoline Receptors; Lipid Metabolism; Male; Metabolic Syndrome; Obesity; Oxazoles; Rats; Rats, Inbred SHR; Receptors, Adrenergic, alpha-2; Receptors, Drug; Rilmenidine; Yohimbine