Association of Endocrine Active Environmental Compounds With Body Mass Index and Weight Loss Following Bariatric Surgery

Harshal Deshmukh; Lesa L. Aylward; Martin Rose; Alwyn Fernandes; Peter Sedman; Natalie J. Thatcher; Stephen L. Atkin; Thozhukat Sathyapalan

Disclosures

Clin Endocrinol. 2020;93(3):280-287. 

In This Article

Discussion

This is the first study in the UK population looking at the association of a suite of lipophilic, persistent chlorinated and brominated biphenyls, dioxins, furans and diphenylethers with BMI as well as changes in their concentration following bariatric surgery and weight loss. We show that several ortho-chlorinated biphenyls and nonortho-chlorinated biphenyls and PCDD/Fs are associated with BMI and that the concentrations of these environmental chemicals in fat tissues increase following bariatric surgery.

Our study showed that BMI was positively associated with selected polychlorinated biphenyls PCBs and structurally related polychlorinated dibenzo-p-dioxins dibenzofurans (PCDD/Fs) whereas BMI was not generally associated with the brominated dioxins (PBDDs), furans (PBDFs), biphenyls (PBBs), and diphenyl ethers (PBDEs) after correction for multiple testing. The positive association between concentrations of many of these compounds and age has been well documented in the literature; however, studies looking at the association with BMI with environmental chemicals have been equivocal.[27] Since the increase in BMI also correlates with an increase in body lipids, the concentrations of environmental chemicals in the body can increase or decrease depending upon the time course of environmental exposure to these compounds, acquisition of body fat and lipophilic properties of these compounds. As a result, it is difficult to establish a causal relationship between these compounds and BMI. A study by Dirinck et al[28] showed negative correlation between BMI, waist, fat mass percentage, total and subcutaneous abdominal adipose tissue, and serum levels of PCB 153, 180, 170 and the sum PCBs but positive association of β-hexachlorocyclohexane (βHCH) with BMI. On the other hand, studies have also indicated that increasing body mass index (BMI) may be associated with increased serum lipid concentrations of dioxins.[14,29–33] Many of these studies have been conducted in occupationally exposed populations who have elevated serum concentrations of PCDD/Fs compared to the general population. Relatively little information is available to assess the impact of obesity on background chlorinated dioxin levels, and no information is available for brominated dioxins. With the increasing prevalence of obesity in the general population in many countries, evaluation of if, and how much, dioxin levels are associated with obesity becomes relevant to risk assessment for these compounds. There are various sources of these endocrine active chemicals, and according to some studies, exposure to chlorinated POPs by the general population continues, mostly through consumption of fatty foods of animal origin. Thus, a high intake of animal source food can lead to higher levels of endocrine active chemicals leading to higher BMI.

The associations between BMI and environmental chemicals during the developmental period and childhood can be explored by prospective cohort studies looking at the exposure to environmental chemicals at birth and follow-up weight in the study participants; however, such studies have been limited. In a Belgian prospective cohort study[34] in the paediatric population, cord blood PCB (congeners 118, 138, 153, 170 and 180) concentrations were associated with increased follow-up BMI. Another study[35] showed that female foetuses with the highest transplacental PCB exposures were heavier for their heights than other girls (at age 11 years) who were not exposed, and however, these associations were only significant in caucasian participants. However, other studies have shown either negative[36] or null associations between PCBs and BMI.[37]

Animal studies have also provided some evidence showing associations with obesity. A study by Ruzzin et al[38] showed that male rats fed a high-fat diet of crude salmon oil (HFC) containing high levels of persistent organic pollutants (POPs) or refined salmon oil (HFR) with significantly lower environmental chemicals levels showed increased abdominal obesity, and elevated levels of diacylglycerol, triacylglycerol and total cholesterol in HFC rats compared with the HFR rats. HFC-fed rats developed insulin resistance, impaired lipid and glucose metabolism, and hepatosteatosis, confirming that chronic exposure to environmental chemicals severely impairs insulin sensitivity and contributes to abdominal obesity in male rats.

A further issue relates to the impact of weight reduction upon the concentration and amount of dioxins in the body. There is the possibility that significant weight reduction could cause release of dioxin from adipose tissue depots, as the adipose tissue is lost, and that the concentrations in blood and adipose tissue of dioxin and other toxic lipophilic chemicals could increase if the dioxin remains in the body as adipose tissue is lost, potentially increasing the internal exposure level for toxicologically relevant tissues or receptors. There is evidence that weight loss is associated with an increase in PCBs and other highly lipophilic contaminants[13–15,39]). However, the factors affecting the degree of increase in concentration, changes after weight loss and other mass balance issues have not been thoroughly assessed to date. The benefits of acute weight loss would be the primary finding but in the long term when weight loss has plateaued then hypothetically the increased concentrations of these chemicals could have a detrimental effect, though longer studies are needed to confirm this.

In this study, we also show that estimated concentrations of selected compounds increased in remaining fat depots following weight loss induced by bariatric surgery. Our findings are in agreement with an earlier study[16,29] which showed that the serum PCB concentrations increased by approximately 50% following weight loss at six months follow-up. The data presented in our study are generally consistent with the hypothesis that compounds stored in fat are mobilized and redistributed into remaining fat tissue following weight loss. There are reports of association of polychlorinated biphenyls (PCBs). Serum persistent organic pollutants (POPs) and serum organohalogen levels are associated with breast cancer,[3] prostate cancer[40,41] and other cancers.[42] It is possible that the increased concentration of these in the body following weight loss could accentuate the endocrine system disrupting and carcinogenic effects of these chemicals in the body.

In our study, the degree of change in observed concentrations of environmental chemicals following weight loss differed substantially by the individual, even taking into account the different amount of weight loss and estimated losses in fat mass. However, for each individual, the degree of change in concentration was very similar across contaminants, suggesting a consistent quantity of release of compound and redeposition into the remaining fat mass regardless of the specific contaminant. This observation suggests that the differing degrees of change in concentration may be related to interindividual differences in the accuracy of the fat mass estimation procedure used. Other possible explanations include a individual differences in elimination half-lives and a small sample size of the follow-up participants.

Our study had several limitations. Since this is a cross-sectional study, we are not able to establish a causal link between environmental chemicals and BMI. It is possible that the association of the environmental chemicals with BMI simply reflects the excess accumulation of lipophilic environmental chemicals in participants with high BMI and high concentration of body lipids. Furthermore, in this cross-sectional study, we are not able to adjust for the time course of lifelong environmental exposure to these chemicals, which are important determinants of their concentration in the body. Also, the scope of this study was limited to investigating the association of these endocrine active chemicals with BMI and changes in their concentration following bariatric surgery. Further studies are needed to investigate whether the accumulation of these chemicals following bariatric surgery increases the likelihood of endocrine or hormonal dysfunction in the long term, though in the short term the beneficial effects of bariatric surgery would be more evident. All the participants from this study were recruited, from Hull and East Riding of Yorkshire, which is a highly stable population epidemiologically; therefore, different environmental exposure is less likely than in a mobile population, but a detailed migratory history was not obtained to confirm this.

However, this study provides first paired liver and adipose tissue samples from adults for a range of environmental chemicals, including some with no previous human liver tissue data. We also show that if an environmental chemical is associated with BMI, this association is likely to be consistent across subcutaneous fat, visceral fat and in liver fat and likely is a consequence of high correlation levels across these depots. We also provide evidence of environmental chemicals redistribution following weight loss, which has implications for patients experiencing significant weight loss, whether following surgery, dietary restriction or secondary to illness. In summary, we show an association between BMI and various polychlorinated biphenyls PCBs and structurally related polychlorinated dibenzo-p-dioxins dibenzofurans (PCDD/Fs) and increased subcutaneous fat concentrations following weight loss. Further molecular, genetic and animal studies are needed to elucidate potential causal associations between these compounds and obesity.

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