Endocrinology & Metabolic Syndrome
Open Access

Endocrine Disrupting Chemicals and their Role in Metabolic Syndrome Pathophysiology

Zeev Estrov^{* *}Correspondence: Zeev Estrov, Department of Endocrinology, University of Majmaah, Al-Majmaah, Saudi Arabia, Email:

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Description

Endocrine Disrupting Chemicals (EDCs) are exogenous compounds that interfere with the normal functioning of the endocrine system, leading to adverse health outcomes. These chemicals are widely present in the environment, including industrial by-products, pesticides, plastics, personal care products, and pharmaceuticals. Over the past few decades, research has increasingly highlighted the role of EDCs in the pathophysiology of Metabolic Syndrome (MetS), a cluster of metabolic abnormalities, including insulin resistance, obesity, dyslipidemia, and hypertension. MetS is a major risk factor for cardiovascular diseases and type 2 diabetes, making it a significant public health concern.

Sources and exposure to EDCs

Humans are exposed to EDCs through multiple routes, including ingestion, inhalation, and dermal absorption. Common EDCs include Bisphenol A (BPA), phthalates, Polychlorinated Biphenyls (PCBs), dioxins, and organochlorine pesticides. BPA, found in plastic containers and food packaging, is one of the most studied EDCs due to its widespread presence and documented effects on metabolic health. Phthalates, used in plastics and cosmetics, and dioxins, released during industrial processes, also pose significant risks. Bioaccumulation of these chemicals in adipose tissue exacerbates their long-term effects, as they can persist in the human body for extended periods.

Mechanisms of EDC-induced metabolic dysfunction

EDCs exert their effects through multiple pathways, disrupting hormone synthesis, secretion, transport, and action. One key mechanism involves interference with nuclear hormone receptors, such as Peroxisome Proliferator-Activated Receptors (PPARs) and estrogen receptors. PPAR-Gamma (γ), in particular, plays a critical role in lipid metabolism and adipogenesis. EDCs can activate or inhibit these receptors, leading to altered lipid storage, insulin sensitivity, and glucose homeostasis.

Furthermore, EDCs can promote oxidative stress and inflammation, both of which are key contributors to metabolic syndrome. For instance, BPA exposure has been shown to increase pro-inflammatory cytokines, such as Tumor Necrosis Factor-Alpha (TNF-α) and Interleukin-6 (IL-6). This inflammation can impair insulin signaling pathways, ultimately resulting in insulin resistance.

Impact of EDCs on obesity and adipogenesis

EDCs are also termed "obesogens" due to their ability to promote fat accumulation and adipocyte differentiation. Chemicals like BPA and phthalates have been shown to enhance adipogenesis by activating PPAR-γ and disrupting leptin signaling, a hormone responsible for appetite regulation and energy balance. This dysregulation leads to increased fat storage and reduced energy expenditure, contributing to obesity-a core component of metabolic syndrome.

Insulin resistance and glucose homeostasis

Insulin resistance is a hallmark of metabolic syndrome, and EDCs play a significant role in its development. BPA, for example, mimics estrogen and binds to estrogen receptors, disrupting insulin signaling pathways in the liver, muscle, and adipose tissue. Similarly, phthalates interfere with glucose metabolism by altering insulin receptor substrate signaling and downstream pathways. These disruptions result in impaired glucose uptake and increased hepatic glucose production, further contributing to hyperglycemia and insulin resistance.

Hypertension and dyslipidemia

EDCs also contribute to hypertension and dyslipidemia, two acute components of metabolic syndrome. Research has shown that exposure to dioxins and PCBs can lead to increased oxidative stress and vascular inflammation, ultimately causing endothelial dysfunction and elevated blood pressure. Additionally, EDCs can disrupt cholesterol and triglyceride metabolism, resulting in dyslipidemia characterized by elevated Low-Density Lipoprotein (LDL) cholesterol and reduced High- Density Lipoprotein (HDL) cholesterol.

Prenatal and early-life exposure

Emerging evidence suggests that prenatal and early-life exposure to EDCs has long-term consequences on metabolic health. During critical windows of development, exposure to these chemicals can cause permanent alterations in gene expression through epigenetic modifications. Studies have demonstrated that prenatal exposure to BPA and phthalates is associated with an increased risk of childhood obesity, insulin resistance, and other metabolic abnormalities later in life.

Public health implications and preventive measures

The widespread presence of EDCs in the environment poses a significant challenge for public health. Regulatory agencies have implemented measures to limit EDC exposure, such as banning BPA in baby bottles and restricting certain pesticide use. However, these measures are often insufficient, and continuous monitoring and stricter regulations are required.

On an individual level, reducing exposure to EDCs involves practical measures such as avoiding plastic containers with BPA, using glass or stainless steel alternatives, reducing consumption of processed foods, and opting for organic produce. Public awareness campaigns are essential to educate communities about the risks of EDC exposure and promote safer practices.

Conclusion

Endocrine disrupting chemicals play a significant role in the pathophysiology of metabolic syndrome through multiple mechanisms, including hormone receptor disruption, oxidative stress, inflammation, and epigenetic modifications. With the rising prevalence of metabolic syndrome globally, addressing EDC exposure must become a priority for public health initiatives. Further research is needed to fully understand the complex interactions between EDCs and metabolic pathways, as well as to develop effective strategies for reducing exposure and mitigating their adverse effects on human health.