Accumulation of organophosphorus pollutants in adipose tissue of obese women - metabolic alterations.

Organophosphorus pesticides (OPPs) and organophosphate esters (OPEs) are organophosphorus compounds created as substitutes for persistent environmental pollutants, namely organochlorines pesticides and brominated flame retardants, respectively. However, there is evidence that organophosphorus compounds are also widespread across the environment and have adverse effects on biota. In humans, OPPs and OPEs were reported to be carcinogenic, neurotoxic, hepatotoxic, nephrotoxic, amongst others. As lipophilic compounds, these accumulate in fat tissues as adipose tissue. Yet biomonitoring studies and analytical methodologies to assess these compounds in the human body are scarce, particularly in adipose tissue. In this study, the presence of six OPPs and seven OPEs was determined in samples of subcutaneous adipose tissue (scAT) and visceral adipose tissue (vAT) from 188 adult obese women. OPPs and OPEs were quantified by gas chromatography (GC) flame photometric detection and confirmed in GC tandem mass spectrometry. The detection frequencies ranged between 0.5-1.6% and 48-53%, respectively for OPPs and OPEs. Organophosphorus pollutants were present in both adipose tissues and median concentrations were 0.008 ± 0.020 µg/g scAT and 0.009 ± 0.020 µg/g vAT. A total of 32 Spearman's correlations were found between organophosphorus pollutants concentrations in adipose tissue and several biochemical parameters (18 positive and 14 negative). Our results show that anthropometric and hormonal parameters, cholesterol, glycaemia, macrominerals, urea and sedimentation velocity might be influenced by the presence of these compounds. The presence of organophosphorus pollutants in the environmental and their possible effect on female metabolic processes is concerning. Particularly because presently OPEs usage is not controlled or limited by any regulation. More studies are needed to fully understand these pollutants behaviour and hazard effects on human health, biota, and the environment so control regulations can be drawn to prevent and lessen their effects.

Adipose tissue fatty acids as biomarkers for metabolic dysfunction in obese females: Implication of menopause and ageing.

Fatty acids (FA) are biomarkers of metabolic dysfunction. Adipose tissue is the largest reservoir of FA and acts differently in obese individuals. Menopause by itself significantly alters metabolism, lipid metabolism dysregulation, and adipose tissue distribution. How adipose tissue FA alters an obese individual's metabolism depending on a female's menopausal status is yet poorly understood. Hence, the subcutaneous (scAT) and visceral adipose tissue (vAT) FA profile for 173 obese premenopausal and postmenopausal women was measured and associated with biochemical parameters. scAT and vAT FA profiles were distinct by themselves and in menopause. In total 816 associations were found with biochemical parameters, where only 58 were independent of the menopausal status. The associations found to emphasize the importance of assessing the adipose tissue FA profile and how their behavior changes with menopause. The FA are crucial in metabolic processes and can be helpful biomarkers in the prevention/treatment and follow-up of female obesity.

Assessment of synthetic musks, polychlorinated biphenyls and brominated flame retardants in adipose tissue of obese northern Portuguese women - Metabolic implications.

Obesity is a worldwide multifactorial disease linked to persistent pollutants exposure amongst other factors. Humans are daily exposed to an assort of pollutants, such as polychlorinated biphenyls, brominated flame retardants and synthetic musks. These, also known as endocrine disruptors, were all found in human adipose tissue, the preferable matrix for the assessment of long-time accumulation. There are several accounts of hazardous effects of polychlorinated biphenyls and brominated flame retardants on the human organism, whereas for synthetic musks little is still known. Hence, in this study, the levels of polychlorinated biphenyls, brominated flame retardants, and synthetic musks were measured in samples of adipose tissue from 188 Obese Portuguese Women (subcutaneous or scAT and visceral or vAT). After which, associations between pollutants levels and several biochemical parameters from assorted of metabolic processes were studied. Brominated flame retardants were not found in any sample analysed, synthetic musks were found in all the samples analysed (100 % detection frequency) with median levels of 0.4 ± 0.6 µg/g in scAT and 0.4 ± 0.7 µg/g in vAT and polychlorinated biphenyls were found in the majority of samples (<90 % detection frequency) with median levels of 0.1 ± 0.3 µg/g in both tissues. Median concentrations of synthetic musks and polychlorinated biphenyls were similar between scAT and vAT. In total 315 associations were achieved with pollutants levels in adipose tissue, including 273 Spearman's correlations (146 negative and 127 positive). Additionally, 3 multiple linear regressions were achieved. Synthetic musks behave differently than polychlorinated biphenyls and other well-known persistent pollutants in the human body. Synthetic musks behaviour is yet poorly known and their high levels and detection frequencies enforces the need for more studies about their impact on human health. Understanding how these chemicals alter the metabolism is crucial knowledge and hopefully will contribute to improving the treatment and follow-up of obesity in the female population.

Brominated flame retardants effect in MCF-7 cells: Impact on vitamin D pathway.

Brominated flame retardants (BFRs) are persistent environmental pollutants, allowing a constant human exposure which carries several health risks, including the occurrence of breast cancer and vitamin D deficiency. Vitamin D inhibits cell growth and is negatively associated with breast cancer risk. The effect of BFRs in breast cancer and vitamin D pathway is still poorly understood. MCF-7 cells were treated with hexabromocyclododecane (HBCD), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (TBB), hexabromobenzene (HBB) and pentabromotoluene (PBT) using short and long-term exposure protocols. Viability, proliferation, migration, cell cycle and gene expression were assessed. Gene expression of hVDBP and hCYP2R1 was also evaluated in hepatocytes. Long-term exposure of MCF-7 cells to HBB increased cell proliferation and migration, consequently increasing MMP-9 expression. The vitamin D pathway was also altered by BFRs: cells appeared less prepared to activate and transport vitamin D and the signaling, action and inactivation mechanisms were diminished in the presence of BFRs. Untreated MCF-7 cells showed cell cycle arrest in phase G0/G1 in the presence of activated vitamin D. However, when MCF-7 cells were exposed to BFRs, cell cycle was arrested in phase G2/M, possibly due to DNA damage. Nonetheless, calcitriol seems to be able to mitigate the effect of some BFRs exposure, e.g. PBT.

Evaluation of the QuEChERS and magnetic micro dispersive solid-phase extraction of brominated flame retardants in red fruits with determination by GC/MS.

A sample preparation method, QuEChERS extraction combined with a magnetic micro dispersive solid phase extraction (MµdSPE), was optimized and evaluated for the trace analysis of 9 brominated flame retardants in red fruit samples (strawberries, blueberries, and raspberries) using gas chromatography-mass spectrometry. Magnetic nanomaterials were used as sorbents providing an extraction of the target compounds. Linearity was established for all the analytes (from 10 to 200 µg kg-1). Seven concentration levels were analyzed with three measurements at each concentration. Linear responses (R2 > 0.99) were obtained, recoveries of all target analytes were within the range of 65-141%, relative standard deviations were <20% at all three spiking levels, while intraday and interday precisions were below 20%. This study demonstrated that the new sample preparation with magnetic nanoparticles could potentially be expanded to extract and pre-concentrate the BFRs in different red fruit samples. The method has been successfully applied to study BFRs in 12 samples from conventional and organic farming.