Abstract

Bisphenols and phthalates, chemicals frequently used in plastic products, promote obesity in cell and animal models. However, these well-known metabolism-disrupting chemicals (MDCs) represent only a minute fraction of all compounds found in plastics. To gain a comprehensive understanding of plastics as a source of exposure to MDCs, we characterized the chemicals present in 34 everyday products using nontarget high-resolution mass spectrometry and analyzed their joint adipogenic activities by high-content imaging. We detected 55,300 chemical features and tentatively identified 629 unique compounds, including 11 known MDCs. Importantly, the chemicals extracted from one-third of the products caused murine 3T3-L1 preadipocytes to proliferate, and differentiate into adipocytes, which were larger and contained more triglycerides than those treated with the reference compound rosiglitazone. Because the majority of plastic extracts did not activate the peroxisome proliferator-activated receptor γ and the glucocorticoid receptor, the adipogenic effects are mediated via other mechanisms and, thus, likely to be caused by unknown MDCs. Our study demonstrates that daily-use plastics contain potent mixtures of MDCs and can, therefore, be a relevant yet underestimated environmental factor contributing to obesity.

Highlights

  • The obesity pandemic generates a considerable burden of disease through comorbidities such as type 2 diabetes, cardiovascular disease, hypertension, nonalcoholic fatty liver disease, stroke, and certain types of cancer.[1]

  • We investigated the underlying mechanism of the adipogenic response by testing whether the extracted plastic chemicals activate the human peroxisome proliferatoractivated receptor gamma (PPARγ) or glucocorticoid receptor (GR)

  • To assess the induction of adipogenesis by the plastic extracts, we present the numbers of adipocytes and mature adipocytes in the cell populations and the total lipid droplet count per image for the highest noncytotoxic concentration (HNC) of each sample

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Summary

Introduction

The obesity pandemic generates a considerable burden of disease through comorbidities such as type 2 diabetes, cardiovascular disease, hypertension, nonalcoholic fatty liver disease, stroke, and certain types of cancer.[1] The number of obese people worldwide has nearly tripled since 1975, and in 2016, more than 41 million children under the age of five were classified as being overweight or obese.[2] This is problematic because a high body mass index (BMI) is one of the top risk factors for deaths,[3] and overweight in childhood or adolescence is a good predictor of adult obesity.[4] a high BMI and the associated comorbidities contributed to four million deaths globally in 2015 with cardiovascular diseases as the leading cause of death, followed by diabetes, chronic kidney diseases, and cancer.[5] This public health problem has been largely attributed to genetic background and changes in lifestyle, such as diet, exercise, sleep deficiency, and aging. This is further supported by epidemiological studies that have linked weight gain in humans to bisphenol A (BPA) exposure,[11] while contradicting outcomes have been reported regarding a link to phthalate exposure.[12−14] Received: September 25, 2021 Revised: December 3, 2021 Accepted: December 27, 2021

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