Endocrine Aspects of Environmental "Obesogen" Pollutants

Abstract

Growing evidence suggests the causal link between the endocrine-disrupting chemicals (EDCs) and the global obesity epidemics, in the context in the so-called "obesogenic environment". Dietary intake of contaminated foods and water, especially in association with unhealthy eating pattern, and inhalation of airborne pollutants represent the major sources of human exposure to EDCs. This is of particular concern in view of the potential impact of obesity on chronic non-transmissible diseases, such as type 2 diabetes, cardiovascular disease, and hormone-sensitive cancers. The key concept is the identification of adipose tissue not only as a preferential site of storage of EDCs, but also as an endocrine organ and, as such, susceptible to endocrine disruption. The timing of exposure to EDCs is critical to the outcome of that exposure, with early lifetime exposures (e.g., fetal or early postnatal) particularly detrimental because of their permanent effects on obesity later in life. Despite that the mechanisms operating in EDCs effects might vary enormously, this minireview is aimed to provide a general overview on the possible association between the pandemics of obesity and EDCs, briefly describing the endocrine mechanisms linking EDCs exposure and latent onset of obesity.

Keywords: endocrine-disrupting chemicals; inflammation; obesity; obesogenic environment.

Figure 1

EDCs are known to activate PPAR-γ, which leads to weight gain in vivo preferentially committing the mesenchymal stem cells toward differentiation into adipocytes regulating the relative expression of PPARγ-induced genes. As the vast majority of EDCs are lipophilic, these compounds might be easily accumulated in the adipose tissue over the years. Thus, a continuous spiral is created, with the increasing burden of EDCs stored in the body fat along with the EDC-induced accrual of adipose tissue. EDCs, endocrine-disrupting chemicals; PPAR-γ, Peroxisome Proliferator-Activated Receptor-γ.

Figure 2

A possible pathway involving BPA, liver-spleen axis, hyperandrogenism, and low-grade inflammation in pathogenesis of the polycystic ovary syndrome taking into account the suggested role of BPA as EDC for the “environmental obesogen hypothesis”, and considering the possible relationship between in utero exposure to BPA and PCOS pathogenesis. Besides a direct hepatotoxic and adipogenetic effect, BPA could act as pro-inflammatory primer, via macrophage activation and pro-inflammatory cytokine hypersecretion, being spleen enlargement as marker of this process, with a possible link with immune/autoimmune derangement in women with PCOS. PCOS exposure to low-chronic BPA doses might initiate or exacerbates obesity and IR, while in turn, BPA influences androgen metabolism. BPA, Bisphenol A; EDCs, endocrine-disrupting chemicals; PCOS, polycystic ovary syndrome; IR, insulin resistance.