Abstract

Since the 1950s, the production of plastics has increased 200-fold, reaching 360 million tonnes in 2019. Plasticizers, additives that modify the flexibility and rigidity of the product, are ingested as they migrate into food and beverages. Human exposure is continuous and widespread; between 75 and 97% of urine samples contain detectable levels of bisphenols and phthalates, the most common plasticizers. Concern over the toxicity of plasticizers arose in the late 1990s, largely focused around adverse developmental and reproductive effects. More recently, many studies have demonstrated that exposure to plasticizers increases the risk for obesity, type 2 diabetes, and cardiovascular disease (CVD). In the 2000s, many governments including Canada, the United States and European countries restricted the use of certain plasticizers in products targeted towards infants and children. Resultant consumer pressure motivated manufacturers to substitute plasticizers with analogues, which have been marketed as safe. However, data on the effects of these new substitutes are limited and data available to-date suggest that many exhibit similar properties to the chemicals they replaced. The adverse effects of plasticizers have largely been attributed to their endocrine disrupting properties, which modulate hormone signaling. Adipose tissue has been well-documented to be a target of the disrupting effects of both bisphenols and phthalates. Since adipose tissue function is a key determinant of cardiovascular health, adverse effects of plasticizers on adipocyte signaling and function may underlie their link to cardiovascular disease. Herein, we discuss the current evidence linking bisphenols and phthalates to obesity and CVD and consider how documented impacts of these plasticizers on adipocyte function may contribute to the development of CVD.

Highlights

  • Cardiovascular diseases (CVD) lead to an estimated 17.9 million deaths annually, making them one of the leading causes of death worldwide.1 The substantial global impact of cardiovascular disease (CVD) is one of the most critical public health issues of our time

  • Worldwide production of bisphenol A (BPA) increased by approximately 2.3 million tons between 2003 and 2011 (Flint et al, 2012) and its consumption is expected to increase at a rate of 3.6% per year through 20232

  • Another study reported an increase in 3T3-L1 differentiation in response to prolonged exposure to the DEHP substitute, DiNP, an effect that was prevented by PPARγ antagonism (Zhang et al, 2019). These findings suggest that phthalates and their substitutes augment in vitro differentiation of adipocyte progenitors

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Summary

INTRODUCTION

Cardiovascular diseases (CVD) lead to an estimated 17.9 million deaths annually, making them one of the leading causes of death worldwide. The substantial global impact of CVD is one of the most critical public health issues of our time. Many of these studies have been conducted in a cross-sectional design, mainly utilizing data from NHANES (LaKind et al, 2012). A cross-sectional study using data from the 2012–2014 Korean National Environmental Health Survey II (n 5,251) reported a significant association between urine MEHHP levels and MetS, defined by NCEP ATP III criteria (Shim et al, 2019) In agreement with these results, James-Todd et al, used NHANES data from 2001 to 2010 (n 2,719) and found that higher concentrations of DEHP metabolites, including MEHP, MEHHP, and MEOHP, increased the odds of developing MetS in males (Shim et al, 2019). While in vitro studies demonstrate a pro-adipogenic effect of plasticizers, more studies are needed to determine if accelerated fat accumulation due to early life exposure leads to the development of obesity and its cardiometabolic complications

Production of Adipokines
Adipose Tissue Inflammation and Oxidative Stress
CONCLUSION
Findings
AUTHOR CONTRIBUTIONS
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