The Role of Persistent Organic Pollutants in Obesity: A Review of Laboratory and Epidemiological Studies

Abstract

Persistent organic pollutants (POPs) are considered as potential obesogens that may affect adipose tissue development and functioning, thus promoting obesity. However, various POPs may have different mechanisms of action. The objective of the present review is to discuss the key mechanisms linking exposure to POPs to adipose tissue dysfunction and obesity. Laboratory data clearly demonstrate that the mechanisms associated with the interference of exposure to POPs with obesity include: (a) dysregulation of adipogenesis regulators (PPARγ and C/EBPα); (b) affinity and binding to nuclear receptors; (c) epigenetic effects; and/or (d) proinflammatory activity. Although in vivo data are generally corroborative of the in vitro results, studies in living organisms have shown that the impact of POPs on adipogenesis is affected by biological factors such as sex, age, and period of exposure. Epidemiological data demonstrate a significant association between exposure to POPs and obesity and obesity-associated metabolic disturbances (e.g., type 2 diabetes mellitus and metabolic syndrome), although the existing data are considered insufficient. In conclusion, both laboratory and epidemiological data underline the significant role of POPs as environmental obesogens. However, further studies are required to better characterize both the mechanisms and the dose/concentration-response effects of exposure to POPs in the development of obesity and other metabolic diseases.

Prenatal Environmental Exposure to Persistent Organic Pollutants and Indices of Overweight and Cardiovascular Risk in Dutch Adolescents

“…Several explanations for the obesogenic effects of POPs have been suggested [ 38 , 39 ]. POPs can interfere with hormonally responsive tissue functions via dysregulation of hormone signaling and cell function [ 38 ].…”

Combinatorial pathway disruption is a powerful approach to delineate metabolic impacts of endocrine disruptors

“…Similarly, BPA or its structural analogues (bisphenols AF, B, E, F and S) and halogenated derivatives [tetrabromobisphenol A (TBBPA) and tetrachlorobisphenol-A], phthalates [e.g. diethylhexyl phthalate (DEHP)], parabens, PFOS, PFOA and organochlorine pesticides such as DDT/DDE and HCB are associated with an increased adipogenesis and subsequently to an increased body weight and other disorders such as inflammation, hyperglycaemia, dyslipidaemia, glucose intolerance and insulin resistance [38][39][40][41][42][43]. For some chemicals such as tetrachlorodibenzo-p-dioxin (TCDD), PCB153, a second hit (e.g.…”

“…(b) At the hepatic level, there are multiple targets of BPA: it behaves as a reverse agonist of CAR [70], a receptor suppressing gluconeogenesis; as a consequence, BPA potentially contributes to hyperglycaemia but it also reduces the level of insulin receptor contributing to insulin resistance [76], which could be enhanced by inflammatory cytokine production [78] and polarisation of KCs to a pro-inflammatory phenotype. (c) BPA promotes in AT, increased adipogenesis associated with increased body weight but also inflammation that contributes to insulin resistance and hyperglycaemia [38][39][40]. BPA and its substitutes (AF, F and S), act by modulating the activity of PPARc; it should be noted that, in this tissue, the effects of the BPA substitute, BPS, are even more powerful and include a robust induction of adipogenic genes such as FABP4, LPL, leptin and perilipin [52].…”

Effect of Pesticides on Peroxisome Proliferator-Activated Receptors (PPARs) and Their Association with Obesity and Diabetes

“…Lately, many epidemiological studies have linked exposure to environmental toxicants such as phthalates, bisphenols, and pesticides to obesity and diabetes [4,5]. The environmental toxicants capable of promoting lipid accumulation and adipogenesis are known as obesogens; some examples are pesticides such as DDT (dichloro diphenyl trichloroethane), DDE (dichloro diphenyl dichloroethylene), HCH (hexachlorocyclohexane), and chlorpyrifos [6,7].…”