Abstract and Introduction
Introduction: The objective of this study was to study associations of a wide range of halogenated biphenyls, dibenzo-p-dioxins, dibenzofurans and diphenylethers with body mass index (BMI) and evaluate changes in their concentration following bariatric surgery.
Methods: Subcutaneous fat, visceral fat and liver tissue samples were collected from 106 patients undergoing Roux-en-Y gastric bypass surgery for weight loss or patients who were undergoing abdominal surgery for nonbariatric reasons. We measured concentrations of an extensive panel of chlorinated and brominated biphenyls, dioxins, and furans, and brominated diphenylethers in the samples. We conducted linear regression to examine associations with BMI, adjusting for age and gender. Changes in concentration for indicator chemicals were evaluated in samples collected following bariatric surgery in a small subpopulation.
Results: After adjustments for age and gender and correction for multiple testing, seven ortho-chlorinated biphenyls, one nonortho-chlorinated biphenyl, four PCDD/Fs and one ortho-brominated biphenyl were associated with BMI. The strongest associations between BMI and lipid-adjusted concentrations were seen with PCB-105 in subcutaneous fat (beta = 16.838 P-val = 1.45E-06) PCB-126 in visceral fat (beta = 15.067 P-val = 7.72E-06) and PCB-118 (beta = 14.101 P-val = 2.66E-05) in liver. The concentrations of sum PCBs, chlorinated toxic equivalent quantity (TEQ's) and brominated compounds increased significantly with weight loss in subcutaneous fat in a group of ten individuals resampled up to five years after bariatric surgery and substantial weight loss.
Conclusion: We show that selected polychlorinated biphenyls PCBs and structurally related polychlorinated dibenzo-p-dioxins dibenzofurans (PCDD/Fs) were associated with BMI. Concentrations of these lipophilic compounds in subcutaneous fat increased following bariatric surgery.
Halogenated biphenyls, dibenzo-p-dioxins, dibenzofurans and diphenylethers are chemicals that can interfere with endocrine systems and are implicated in the pathogenesis of obesity, cancer, birth defects and other developmental disorders.[1–5] There are increasing concerns that some of these chemicals can interfere with regulatory processes involved in lipid metabolism and in the control of adipocyte function resulting in excess weight and obesity.[6,7] While some of these chemicals are of natural origin, the majority are synthetic chemicals, which have been released by human activities into the environment. Among the chemicals in this broad category are polychlorinated biphenyls (PCBs) and structurally related polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), the brominated dioxins (PBDDs), furans (PBDFs), biphenyls (PBBs), and diphenyl ethers (PBDEs).[8,9] The patterns of distribution of these chemicals in the body have been studied in numerous species. These chemicals are highly lipophilic and tend to distribute in the body primarily on the basis of the lipid content of the tissue, with data indicating that in general, the concentration of these compounds in lipid throughout the body is usually very similar. PCDD/Fs, PBDD/Fs and coplanar PCBs are also found in liver tissue as they bind to a specific protein, cytochrome p4501a2, which is present in the liver and can be induced by dioxin activation of the aryl hydrocarbon receptor.[11,12] As a result, hepatic concentrations of these compounds can significantly exceed the concentrations expected on the basis of the lipid content of the liver.
Concentrations of many of these environmental chemicals have been monitored in the blood in the US population through the US National Health and Nutrition Examination Survey (NHANES), however, to our knowledge, there have been no systematic biomonitoring studies for chlorinated dioxins in UK populations and there are no UK studies looking at the association of environmental chemicals with BMI and obesity. Furthermore, since the concentrations of these compounds vary with the lipid content in the body, there are concerns that their concentrations might increase in the body following rapid weight lipid loss following procedures such as bariatric surgery.[13–15] There are limited data looking at the changes in the body concentrations of these environmental chemicals following bariatric surgery and no data looking at the changes of these in liver tissue following weight loss.[16,17] For example, Jansen A et.al. analysed 17 different polyfluoroalkylated substances (PFASs) to assess the effect of weight loss before and one year after bariatric surgery, and showed that the plasma levels of all PFASs decreased up to 4%-34%. Another study examined 17 persistent organic pollutants (POPs) and 13 PFAA at baseline and following bariatric surgery and showed that there was a significant increase in POP levels in response obesity surgery.
The prevalence of obesity is increasing in the Western world, and genetic factors explain only a small proportion of the heritability of BMI/obesity.[20,21] It is therefore important to investigate the association of known potentially endocrine active compounds with BMI. The objectives of this study were (a) to look at the association of selected persistent lipophilic environmental chemicals with BMI and (b) compare the concentration of these compounds in the body before and after bariatric surgery in a subset of the study population.
Clin Endocrinol. 2020;93(3):280-287. © 2020 Blackwell Publishing