Relation of C-reactive protein to body fat distribution and features of the metabolic syndrome in Europeans and South Asians.

OBJECTIVE: To investigate the association between circulating C-reactive protein (CRP) concentrations and indices of body fat distribution and the insulin resistance syndrome in South Asians and Europeans. DESIGN: : Cross-sectional study. SUBJECTS: A total of 113 healthy South Asian and European men and women in West London (age 40-55 y, body mass index (BMI) 17-34 kg/m(2)). MEASUREMENTS: Fatness and fat distribution parameters (by anthropometry, dual-energy X-ray absorptiometry and abdominal CT scan); oral glucose tolerance test with insulin response; modified fat tolerance test; and CRP concentration by sensitive ELISA. RESULTS: Median CRP level in South Asian women was nearly double that in European women (1.35 vs 0.70 mg/1, P=0.05). Measures of obesity and CRP concentration were significantly associated in both ethnic groups. The correlation to CRP was especially strong among South Asians (P0.15). CONCLUSION: We suggest that adiposity and in particular visceral adipose tissue is a key promoter of low-grade chronic inflammation. This observation may in part account for the association of CRP with markers of the metabolic syndrome. Future studies should confirm whether CRP concentrations are elevated in South Asians and whether losing weight by exercise or diet, or reduction in visceral fat mass, is associated with reduction in plasma CRP concentrations

The endocanabinnoid system and diabetes - critical analyses of studies conducted with rimonabant

Rimonabant is the first CB1 receptor inhibitor available in the Brazilian market. This new drug has been approved for the treatment of obese or overweight patients associated with cardiovascular risk factors. In this article it is compared the effects of rimonabant treatment in obese patients with cardiovascular risk factors to usual obesity pharmacological treatment

Drugs Associated with More Suicidal Ideations Are also Associated with More Suicide Attempts

In randomized controlled trials (RCTs), some drugs, including CB1 antagonists for obesity treatment, have been shown to cause increased suicidal ideation. A key question is whether drugs that increase or are associated with increased suicidal ideations are also associated with suicidal behavior, or whether drug-induced suicidal ideations are unlinked epiphenomena that do not presage the more troubling and potentially irrevocable outcome of suicidal behavior. This is difficult to determine in RCTs because of the rarity of suicidal attempts and completions.To determine whether drugs associated with more suicidal ideations are also associated with more suicide attempts in large spontaneous adverse event (AE) report databases.Generalized linear models with negative binomial distribution were fitted to Food and Drug Administration (FDA) Adverse Event (AE) Reporting System (AERS) data from 2004 to 2008. A total of 1,404,470 AEs from 832 drugs were analyzed as a function of reports of suicidal ideations; other non-suicidal adverse reactions; drug class; proportion of reports from males; and average age of subject for which AE was filed. Drug was treated as the unit of analysis, thus the statistical models effectively had 832 observations.Reported suicide attempts and completed suicides per drug.832 drugs, ranging from abacavir to zopiclone, were evaluated. The 832 drugs, as primary suspect drugs in a given adverse event, accounted for over 99.9% of recorded AERS. Suicidal ideations had a significant positive association with suicide attempts (p<.0001) and had an approximately 131-fold stronger magnitude of association than non-suicidal AERs, after adjusting for drug class, gender, and age.In AE reports, drugs that are associated with increased suicidal ideations are also associated with increased suicidal attempts or completions. This association suggests that drug-induced suicidal ideations observed in RCTs plausibly represent harbingers that presage the more serious suicide attempts and completions and should be a cause for concern

TNF-alpha Is Required for the Attraction of Mesenchymal Precursors to White Adipose Tissue in Ob/ob Mice

Most adult tissues harbour a stem cell subpopulation (Mesenchymal Precursors or MPs) that represent a small proportion of the total cell number and have the potential to differentiate into several cell types within the mesenchymal lineage. In adipose tissue, adipocytes account for two-thirds of the total cell number. The remaining cells include blood and endothelial cells, along with adipocyte precursors (adipose MPs). Obesity is defined as an excess of body fat that frequently results in a significant impairment of health. The ob/ob mice bear a mutation in the ob gene that causes a deficiency in the hormone leptin and hence obesity. Here, we present evidence that ob/ob mice have a dramatic decrease in the resident MP pool of several tissues, including squeletal muscle, heart, lung and adipose tissue. Moreover, we show that that there is a migration of MP cells from distant organs, as well as homing of these cells to the adipose tissue mass of the ob/ob mice. We call this process adipotaxis. Once in the adipose tissue, migrant MPs undergoe adipose differentiation, giving rise to new differentiated adipocytes within the adipose mass. Finally, we provide evidence that adipotaxis is largely explained by the production of high levels of Tumor Necrosis Factor-alpha (TNF-α) within the ob/ob adipose tissue. The therapeutic implications for human obesity as well as for regenerative medicine are further discussed in this paper

Plasma triglyceride concentrations are rapidly reduced following individual bouts of endurance exercise in women

It is known that chronic endurance training leads to improvements in the lipoprotein profile, but less is known about changes that occur during postexercise recovery acutely. We analyzed triglyceride (TG), cholesterol classes and apolipoproteins in samples collected before, during and after individual moderate- and hard-intensity exercise sessions in men and women that were isoenergetic between intensities. Young healthy men (n = 9) and young healthy women (n = 9) were studied under three different conditions with diet unchanged between trials: (1) before, during and 3 h after 90 min of exercise at 45% VO2peak (E45); (2) before, during and 3 h after 60 min of exercise at 65% VO2peak (E65), and (3) in a time-matched sedentary control trial (C). At baseline, high-density lipoprotein cholesterol (HDL-C) was higher in women than men (P < 0.05). In men and in women, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), HDL-C, apolipoprotein A-I (apoA-I), apolipoprotein B (apoB), and LDL peak particle size were unaltered by exercise either during exertion or after 3 h of recovery. In women, but not in men, average plasma TG was significantly reduced below C at 3 h postexercise by approximately 15% in E45 and 25% in E65 (P < 0.05) with no significant difference between exercise intensities. In summary, plasma TG concentration rapidly declines following exercise in women, but not in men. These results demonstrate an important mechanism by which each individual exercise session may incrementally reduce the risk for cardiovascular disease (CVD) in women

Waist circumference cut-off values for the prediction of cardiovascular risk factors clustering in Chinese school-aged children: a cross-sectional study

Background: Waist circumference has been identified as a valuable predictor of cardiovascular risk in children. The development of waist circumference percentiles and cut-offs for various ethnic groups are necessary because of differences in body composition. The purpose of this study was to develop waist circumference percentiles for Chinese children and to explore optimal waist circumference cut-off values for predicting cardiovascular risk factors clustering in this population.----- ----- Methods: Height, weight, and waist circumference were measured in 5529 children (2830 boys and 2699 girls) aged 6-12 years randomly selected from southern and northern China. Blood pressure, fasting triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and glucose were obtained in a subsample (n = 1845). Smoothed percentile curves were produced using the LMS method. Receiver-operating characteristic analysis was used to derive the optimal age- and gender-specific waist circumference thresholds for predicting the clustering of cardiovascular risk factors.----- ----- Results: Gender-specific waist circumference percentiles were constructed. The waist circumference thresholds were at the 90th and 84th percentiles for Chinese boys and girls respectively, with sensitivity and specificity ranging from 67% to 83%. The odds ratio of a clustering of cardiovascular risk factors among boys and girls with a higher value than cut-off points was 10.349 (95% confidence interval 4.466 to 23.979) and 8.084 (95% confidence interval 3.147 to 20.767) compared with their counterparts.----- ----- Conclusions: Percentile curves for waist circumference of Chinese children are provided. The cut-off point for waist circumference to predict cardiovascular risk factors clustering is at the 90th and 84th percentiles for Chinese boys and girls, respectively

Accurate Inference of Subtle Population Structure (and Other Genetic Discontinuities) Using Principal Coordinates

Accurate inference of genetic discontinuities between populations is an essential component of intraspecific biodiversity and evolution studies, as well as associative genetics. The most widely-used methods to infer population structure are model-based, Bayesian MCMC procedures that minimize Hardy-Weinberg and linkage disequilibrium within subpopulations. These methods are useful, but suffer from large computational requirements and a dependence on modeling assumptions that may not be met in real data sets. Here we describe the development of a new approach, PCO-MC, which couples principal coordinate analysis to a clustering procedure for the inference of population structure from multilocus genotype data.PCO-MC uses data from all principal coordinate axes simultaneously to calculate a multidimensional "density landscape", from which the number of subpopulations, and the membership within subpopulations, is determined using a valley-seeking algorithm. Using extensive simulations, we show that this approach outperforms a Bayesian MCMC procedure when many loci (e.g. 100) are sampled, but that the Bayesian procedure is marginally superior with few loci (e.g. 10). When presented with sufficient data, PCO-MC accurately delineated subpopulations with population F(st) values as low as 0.03 (G'(st)>0.2), whereas the limit of resolution of the Bayesian approach was F(st) = 0.05 (G'(st)>0.35).We draw a distinction between population structure inference for describing biodiversity as opposed to Type I error control in associative genetics. We suggest that discrete assignments, like those produced by PCO-MC, are appropriate for circumscribing units of biodiversity whereas expression of population structure as a continuous variable is more useful for case-control correction in structured association studies