Obesity treatment and cardiovascular prevention in mentally retarded subjects.
Zoppo A, Asteria C.
1Department of Experimental Endocrinology and Cardiovascular Prevention, IRCCS MultiMedica, Sesto San Giovanni, Milan, Italy.
Infection-induced inflammatory response of adipocytes in vitro.
Background:Abdominal obesity plays an important role in the development of insulin resistance, diabetes mellitus and atherosclerosis. The exact pathophysiological mechanisms are unclear but adipocyte dysfunction is thought to be crucial. Infections are associated with the development of atherosclerosis as well as diabetes. In this study we investigated whether adipocytes can be infected and whether this results in production of inflammatory cytokines relevant for the development of atherosclerosis and diabetes.Methods:Pre-adipocytes were cultured and differentiated into mature adipocytes in vitro. Adipocytes and pre-adipocytes were incubated with infective and heat-inactivated Chlamydia pneumoniae, cytomegalovirus (CMV), adenovirus (Ad) subtypes 2 and 36, influenza A and respiratory syncitial virus (RSV). After 48 h, adiponectin, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and plasminogen activator inhibitor-1 (PAI-1) were measured in supernatants.Results:Infection of adipocytes with Ad-36, CMV and RSV resulted in increased IL-6 production from 192+/-22 pg ml(-1) (uninfected) to 1030+/-86 pg ml(-1), 838+/-59 pg ml(-1) and 1241+/-191 pg ml(-1), respectively (all P<0.01 vs control). In addition, Ad-36 infection slightly reduced PAI production in adipocytes (285+/-26.8 ng ml(-1) vs uninfected: 477+/-71.2 ng ml(-1); P=0.05) and pre-adipocytes (709+/-43.3 ng ml(-1) vs uninfected: 1071+/-71.8 ng ml(-1); P<0.01). In contrast, human Ad type 2 did not exert any effect on IL-6 or PAI production. None of the microorganisms induced significant changes in adiponectin and/or TNF-alpha production.Conclusions:Adipocytes can be infected with several microorganisms in vitro. Infection of adipocytes with Ad-36, but not Ad-2 leads to increased production of IL-6 which might contribute to chronic low-grade inflammation, a process known to be involved in the development of cardiovascular diseases and type 2 diabetes.International Journal of Obesity advance online publication, 18 March 2008; doi:10.1038/ijo.2008.36.
Bouwman JJ, Visseren FL, Bouter KP, Diepersloot RJ.
1Department of Medical Microbiology and Immunology, Diakonessen Hospital Utrecht, Bosboomstraat, Utrecht, The Netherlands.
Sleep patterns and television viewing in relation to obesity and blood pressure: evidence from an adolescent Brazilian birth cohort.
Background:Disruption of circadian rhythms has been associated with obesity in children and adolescents, and with hypertension in adults, in industrialized populations.Objective:We examined cross-sectional associations between sleep duration or television viewing and obesity and blood pressure in Brazilian adolescents.Design:The sample consisted of 4452 adolescents aged 10-12 years participating in a prospective birth cohort study in Pelotas, Brazil. Sleep duration and television viewing were determined through questionnaires. Obesity was assessed using international cut-offs for body mass index (BMI), and body fatness by skinfold thicknesses. Blood pressure was measured using a validated monitor.Results:Short sleep duration was associated with increased BMI, skinfolds, systolic blood pressure, activity levels and television viewing. Each hour of sleep reduced BMI by 0.16 kg/m(2) (s.e. 0.04), and was associated with odds ratio for obesity of 0.86 (s.e. 0.04), both P<0.001. Television viewing was associated with increased BMI and skinfolds, and increased blood pressure. The effects of sleep duration and television viewing on obesity were independent of one another. Their associations with blood pressure were mediated by body fatness.Conclusions:Both short sleep duration and increased television viewing were associated with greater body fatness, obesity and higher blood pressure, independently of physical activity level. These associations were independent of maternal BMI, identified in other studies as the strongest predictor of childhood obesity. Our study shows that behavioural factors associated with metabolic risk in industrialized populations exert similar deleterious effects in a population undergoing nutritional transition and suggest options for public health interventions.International Journal of Obesity advance online publication, 18 March 2008; doi:10.1038/ijo.2008.37.
Wells JC, Hallal PC, Reichert FF, Menezes AM, Araújo CL, Victora CG.
1Childhood Nutrition Research Centre, Institute of Child Health, London, UK.
Genomewide association for schizophrenia in the CATIE study: results of stage 1.
Little is known for certain about the genetics of schizophrenia. The advent of genomewide association has been widely anticipated as a promising means to identify reproducible DNA sequence variation associated with this important and debilitating disorder. A total of 738 cases with DSM-IV schizophrenia (all participants in the CATIE study) and 733 group-matched controls were genotyped for 492 900 single-nucleotide polymorphisms (SNPs) using the Affymetrix 500K two-chip genotyping platform plus a custom 164K fill-in chip. Following multiple quality control steps for both subjects and SNPs, logistic regression analyses were used to assess the evidence for association of all SNPs with schizophrenia. We identified a number of promising SNPs for follow-up studies, although no SNP or multimarker combination of SNPs achieved genomewide statistical significance. Although a few signals coincided with genomic regions previously implicated in schizophrenia, chance could not be excluded. These data do not provide evidence for the involvement of any genomic region with schizophrenia detectable with moderate sample size. However, a planned genomewide association study for response phenotypes and inclusion of individual phenotype and genotype data from this study in meta-analyses hold promise for eventual identification of susceptibility and protective variants.Molecular Psychiatry advance online publication, 18 March 2008; doi:10.1038/mp.2008.25.
Sullivan PF, Lin D, Tzeng JY, van den Oord E, Perkins D, Stroup TS, Wagner M, Lee S, Wright FA, Zou F, Liu W, Downing AM, Lieberman J, Close SL.
[1] 1Departments of Genetics, Psychiatry, and Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA [2] 2Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Glutamate as a spectroscopic marker of hippocampal structural plasticity is elevated in long-term euthymic bipolar patients on chronic lithium therapy and correlates inversely with diurnal cortisol.
While an excess of glucocorticoids is associated with hippocampal pathology in mood disorders, lithium exerts robust neuroprotective and neurotrophic effects. Here, 21 stably remitted bipolar I patients who had been on chronic lithium maintenance therapy, on average, for more than a decade, and 19 carefully matched healthy controls were studied using 3 T (1)H-magnetic resonance spectroscopy of left and right hippocampus. Salivary cortisol samples were obtained to assess activity of the hypothalamus-pituitary-adrenal system. Absolute concentrations of N-acetylaspartate (NAA), choline-containing compounds and total creatine were similar in euthymic bipolar patients and healthy controls. Hippocampal glutamate concentrations were significantly increased as an effect of patient status (patients>controls) and laterality (left hippocampus>right hippocampus). Hippocampal glutamate content (Glu) was strongly correlated with NAA. Across groups and within the patient group, diurnal saliva cortisol levels showed a significant inverse relationship with both Glu and NAA. Taken together, these results add to the concept of bipolar disorder as an illness involving disturbed hippocampal structural plasticity under the opposing influences of lithium and glucocorticoids.Molecular Psychiatry advance online publication, 18 March 2008; doi:10.1038/mp.2008.26.
Colla M, Schubert F, Bubner M, Heidenreich JO, Bajbouj M, Seifert F, Luborzewski A, Heuser I, Kronenberg G.
1Department of Psychiatry, Charité, Campus Benjamin Franklin, Berlin, Germany.
Mode of action of mood stabilizers: is the arachidonic acid cascade a common target?
Bipolar disorder is a major medical, social and economic burden worldwide. However, the mechanisms of action of effective antibipolar disorder drugs remain elusive. In this paper, we review studies using a neuropharmacological approach in unanesthetized rats, combined with kinetic, biochemical and molecular biology techniques, showing that chronic administration of three Food and Drug Administration-approved mood stabilizers (lithium, valproate and carbamazepine) at therapeutically relevant doses, selectively target the brain arachidonic acid (AA) cascade. Whereas chronic lithium and carbamazepine decrease the binding activity of activator protein-2 and in turn the transcription, translation and activity of its AA-selective calcium-dependent phospholipase A(2) gene product, valproate appears to be a non-competitive inhibitor of long-chain acyl-CoA synthetase. The net overlapping effects of the three drugs are decreased turnover of AA but not of docosahexaenoic acid in rat brain phospholipids, and decreased brain cyclooxygenase-2 and prostaglandin E(2). Although these observations support the hypothesis proposed by Rapoport and colleagues that the AA cascade is a common target of mood stabilizers, this hypothesis is not necessarily exclusive of other targets. Targeting the AA cascade with drugs or diet may be a useful therapeutic approach in bipolar disorder, and examining the AA cascade in patients might help in better understanding the disease.Molecular Psychiatry advance online publication, 18 March 2008; doi:10.1038/mp.2008.31.
Rao JS, Lee HJ, Rapoport SI, Bazinet RP.
1Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
