New Evidence on BPA’s Role in Adipose Tissue Development of Proinflammatory Processes and Its Relationship with Obesity

Abstract

Bisphenol A (BPA) is a xenobiotic with endocrine disruptor properties which interacts with various receptors, eliciting a cellular response. In the plastic industry, BPA is widely used in the production of polycarbonate and epoxy-phenolic resins to provide elastic properties. It can be found in the lining of canned foods, certain plastic containers, thermal printing papers, composite dental fillings, and medical devices, among other things. Therefore, it is a compound that, directly or indirectly, is in daily contact with the human organism. BPA is postulated to be a factor responsible for the global epidemic of obesity and non-communicable chronic diseases, belonging to the obesogenic and diabetogenic group of compounds. Hence, this endocrine disruptor may be responsible for the development of metabolic disorders, promoting in fat cells an increase in proinflammatory pathways and upregulating the expression and release of certain cytokines, such as IL6, IL1β, and TNFα. These, in turn, at a systemic and local level, are associated with a chronic low-grade inflammatory state, which allows the perpetuation of the typical physiological complications of obesity.

The Role of Endocrine Disruptors Bisphenols and Phthalates in Obesity: Current Evidence, Perspectives and Controversies

“…BPA and phthalates may interact with several nuclear hormone receptors including ERα and ERβ, with an affinity being 10 3 –10 4 times lower compared to 17β-estradiol (E2), androgen receptor (AR), progesterone receptor (PR), glucocorticoid receptor (GR), thyroid hormone receptors (TRα and TRβ), G-protein-coupled receptor 30 (GPR30), estrogen-related γ receptor (ERR-γ), mineralocorticoid receptor (MR), peroxisome-proliferator-activated receptors (PPARs) and retinoid receptors [ 83 , 84 , 85 , 86 , 87 ]. Obesogenic EDCs such as BPA and phthalates may be implicated in the etiopathogenesis of obesity and associated metabolic disorders by (1) increasing the number and size of adipocytes through the regulation of genes involved in adipogenesis; (2) modulating epigenetic pathways during development, enhancing susceptibility to obesity; (3) impacting neuroendocrine signals responsible for appetite and satiety; (4) promoting a proinflammatory milieu in adipose tissue and inducing a state of chronic subclinical inflammation; (5) dysregulating gut microbiome and immune homeostasis; and (6) inducing dysfunction in thermogenic adipose tissues.…”

“…BPA and phthalates may induce the expression and secretion of certain proinflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α and downregulate the expression of anti-inflammatory adipokines such as adiponectin, leading to a sustained low-grade inflammation both locally and systematically, adipose dysfunction and insulin resistance [ 84 , 116 , 117 ]. Nevertheless, the mechanisms implicated in metabolic inflammation are still under investigation.…”

“…Nevertheless, the mechanisms implicated in metabolic inflammation are still under investigation. The majority of in vitro studies in 3T3-L1 cells and in adipocytes derived from subcutaneous tissues have shown that exposure to 1 nM BPA induced an increase in IL-6 and interferon (IFN)-γ while prolonged exposure upregulated the mRNA levels of IL-6, IL-1β, IFN-γ and monocyte chemoattractant protein-1 (MCP1), which were reversed after BPA removal [ 84 , 118 ]. These results were confirmed in some animal studies; however, the effect of BPA depends on caloric intake, diet composition and gender [ 84 ].…”

“…The majority of in vitro studies in 3T3-L1 cells and in adipocytes derived from subcutaneous tissues have shown that exposure to 1 nM BPA induced an increase in IL-6 and interferon (IFN)-γ while prolonged exposure upregulated the mRNA levels of IL-6, IL-1β, IFN-γ and monocyte chemoattractant protein-1 (MCP1), which were reversed after BPA removal [ 84 , 118 ]. These results were confirmed in some animal studies; however, the effect of BPA depends on caloric intake, diet composition and gender [ 84 ]. Furthermore, BPA and its substitutes could promote macrophage polarization toward the proinflammatory M1 subtype, which may be reversed by ERα inhibition in the case of BPF [ 119 ].…”

“…BPA and certain phthalates may also enhance the generation of reactive oxygen species (ROS), which is crucial in cellular stress and the progression of inflammation [ 120 , 121 ]. Finally, in many epidemiological studies, urinary and plasma BPA correlated positively with somatometric indices, such as BMI and waist circumference (WC); proinflammatory biomarkers, including IL-17, a cytokine implicated in chronic inflammation; and glycemic indices (insulin and glucose) [ 84 , 122 , 123 , 124 ].…”