The Role of Endocrine Disruptors on Metabolic Dysfunction

Abstract

Abstract:Abdominal obesity appears to be an important component of the metabolic syndrome (MetS), in which along with insulin resistance, hypertension and dyslipidaemia represents an increased risk for developing cardiovascular diseases and type 2 diabetes (T2D). The aetiology of obesity and its comorbidities is multifactorial, but despite the evidence of traditional contributing factors, the role of environmental toxicants with endocrine disrupting activity has been recently highlighted. Indeed, even small concentrations of these endocrine disrupting chemicals (EDCs) have the ability to cause severe health damages. In this revision, we focused our attention on the mechanisms of action and impact of EDCs exposure as a contributor to the present epidemics of obesity and MetS.The "environmental obesogens" hypothesis associates environmental EDCs to the disruption of energy homeostasis, with recent studies demonstrating the ability of these compounds to modulate the adipocyte biology. On the other hand, the distinct distribution pattern observed between two metabolically distinct AT depots (visceral and subcutaneous) and subsequent repercussion in the aggravation of metabolic dysfunction in a context of obesity, provides accumulating evidence to hypothesise that EDCs might have an important "environmental dysmetabolism" effect.However, in addition to adulthood exposure, the perinatal effects are very important, since it may allow a change in the metabolic programming, promoting the further development of obesity and MetS. Therefore, additional research directed at understanding the nature and action of EDCs will illuminate the connection between health and the environment and the possible effects triggered by these compounds in respect to public health.

Adipose tissue dysfunction as a central mechanism leading to dysmetabolic obesity triggered by chronic exposure to p,p’-DDE

“…Concerns have focused on the hypothesis that exposure to environmental endocrine-disrupting chemicals (EDCs) may be involved in the rise of obesity and MetS epidemic observed worldwide in the last 40 years. In particular, the man-made lipophilic persistent organic pollutants (POPs) with hormone-like activity (endocrine disruptors) can lead to an environmental disruption of metabolism and putative diabetogenic effect 5 , 7 – 11 . POPs are bioaccumulated and biomagnified in the food chain and can be found in the adipose tissue (AT) of virtually all human populations 12 , functioning not only as a reservoir and a source of chronic internal exposure, but also as a possible tissue target of their disruptive effects 13 , 14 .…”

“…Studies such as those developed by Ruzzin et al . where dietary supplementation with salmon oil contaminated with a mixture of POPs in conjunction with high-fat (HF) diet feeding promoted the development of obesity and T2D in a rodent model 25 , 26 , led to the proposition of a broader metabolism disrupting chemical hypothesis where ECDs act as metabolic disruptors that increase the susceptibility to metabolic diseases 7 , 10 , 27 , 28 . A recent publication reviewed the putative mechanisms of metabolic disruption 28 , highlighting the effects on adipogenesis and adipokine production 29 , 30 , neuroendocrine control of feeding and metabolism 31 , 32 , energy homeostasis and T2D trough alteration of insulin action, glucose disposal and beta cell survival and function 33 , as well as hepatic steatosis 34 , and hyperlipidemia 35 .…”

“…Involved molecular mechanism encompass the alteration of hormonal and homeostatic systems related to sex hormones (e.g. estrogens and androgens, thyroid function and corticosteroids) acting through nuclear receptors, nonnuclear steroid hormone receptors, nonsteroid receptors (for example, neurotransmitter receptors), orphan receptors (such as aryl hydrocarbon receptor, AhR), endoplasmic reticulum and oxidative stress, inflammatory disruption and epigenetic changes 7 , 28 .…”

Persistent organic pollutants (POPs) increase rage signaling to promote downstream cardiovascular remodeling

“…Since POPs exposure has been positively correlated with hyperglycemia and T2DM, and T2DM complications, including cardiac remodeling as indicated by left ventricular function and/or hypertrophy as described in previous studies, we aimed to determine the role of POPs exposure and the potential mechanisms responsible for increased incidence of maladaptive responses resulting from AGE-RAGE signaling. 7,10,36 The AGE-RAGE signaling cascade activation has been shown to increase proinflammatory and oxidative stress modulators, such as NF-κB, SOD-1, and SOD-2, to adapt to changes in inflammation and ROS levels. 19,26 NF-κB protein expression was shown to be significantly diminished in ob/ob-POPs mice.…”

“…These observations are the first of its kind to suggest a possible role for POPs as a promoter of the AGE‐RAGE signaling cascade and subsequent cardiac remodeling. Since POPs exposure has been positively correlated with hyperglycemia and T2DM, and T2DM complications, including cardiac remodeling as indicated by left ventricular function and/or hypertrophy as described in previous studies, we aimed to determine the role of POPs exposure and the potential mechanisms responsible for increased incidence of maladaptive responses resulting from AGE‐RAGE signaling …”