Author: Zheng Jinwu Since 1975, the number of obese people in the world has almost tripled, and more than 41 million children under the age of 5 are classified as overweight or obese. A high body mass index (BMI) is one of the leading risk factors for death, causing millions of deaths worldwide each year. Obesity is a public health problem that is largely attributed to genetic background and lifestyle changes, such as uncontrolled eating, lack of exercise, and insufficient sleep. However, epidemiological evidence shows that these factors are insufficient to explain the scale and speed of the obesity epidemic. Therefore, identifying and clarifying other environmental factors besides lifestyle is crucial to controlling obesity. Researchers at the Norwegian University of Science and Technology have discovered that plastic consumer products contain potent metabolic disruptor compounds (MDC). After exposure to MDC, mouse 3T3-L1 preadipocytes differentiate into adipocytes and accumulate triglycerides, eventually forming similar mature white adipocytes. Considering that humans are often exposed to large amounts of plastic products, researchers speculate that plastic chemicals may accelerate the formation of obesity in the human body. Recently, the research results were published in the journal Environmental Science and Technology. Lipogenic activity of plastic consumer products Studies have shown that chemicals such as bisphenols and phthalates promote obesity in cells and animal models. "However, MDCs such as bisphenols and phthalates only account for a small part of all compounds in plastics." Johannes Volk, the first author of the paper, said that considering the chemical complexity of plastic consumer products, bisphenols and phthalates are just the "tip of the iceberg" in their chemical composition. To gain a comprehensive understanding of plastics as a source of exposure to MDCs, the researchers analyzed the chemicals present in 34 everyday plastic consumer products using non-targeted high-resolution mass spectrometry and analysed their joint adipogenic activity by high-content imaging. "We detected 55,300 chemical features and preliminarily identified 629 unique compounds, including 11 known MDCs," Volk said. Further research showed that chemicals extracted from one-third of plastic consumer products could cause mouse 3T3-L1 preadipocytes to proliferate and differentiate into adipocytes; these cells were larger and contained more triglycerides than cells treated with the control compound rosiglitazone. "Our study shows that everyday plastics contain a potent mix of MDCs and may therefore be a relevant but underestimated environmental factor contributing to obesity," says Volk. In fact, many obesogens are endocrine disruptors that interfere with normal endocrine regulation. In cell and animal experiments, significant endocrine disruptors, such as the pesticide dichlorodiphenyltrichloroethane (DDT) and plastic chemicals bisphenols and phthalates, can disrupt metabolic function or promote obesity. In addition, unhealthy or dysfunctional fat cells are part of the obese phenotype. The study found that fat cells exposed to plastic chemicals tended to appear larger and contain more triglycerides. These results suggest that exposure to plastic chemicals may also shift fat cells toward an unhealthy phenotype. Plastic products are usually composed of one or more polymers, a variety of intentionally added substances (such as fillers or additives), and unintentionally added substances (such as residues from the production process). According to statistics, there are more than 4,000 substances in plastic food packaging alone, and empirical data show that there are more chemicals in plastics than currently known. Carol, an expert from the U.S. Green Science Policy Institute, pointed out in a comment that this study provides new ideas for revealing the obesity epidemic; in daily life, people should also try to choose products made of non-plastic materials. Different potential mechanisms PPARγ is a key regulator of adipogenesis and many MDCs that induce adipogenesis can also activate PPARγ. The researchers noted that although PPARγ activation is widely believed to be the main mechanism by which artificial chemicals trigger adipogenesis, most plastic samples did not actually activate the receptor, with high PPARγ activity only in a few cases. In addition, some samples activated PPARγ but did not work in the adipogenesis assay. GR is another important nuclear receptor involved in adipogenesis, and various MDCs can activate GR. However, none of the plastic extracts could activate GR. The researchers therefore believe that the adipogenic effect of plastic extracts does not necessarily rely on direct activation of PPARγ, but may also involve other mechanisms. "Elucidating the mechanism by which plastic chemicals induce adipogenesis is very complicated because we have to deal with two 'black boxes', namely the complex chemical mixture present in plastics and the multiple potential mechanisms of adipogenesis in 3T3-L1 cells." Volk said in the article that if these two issues are not clarified, it is impossible to determine what the adipogenic mechanism of plastic extracts is. In addition to PPARγ and GR, agonists of various other nuclear receptors, such as retinoid X receptor α, estrogen receptor, androgen receptor, liver X receptor, and thyroid β receptor, have also been shown to contribute to adipogenesis. Given the diversity of compounds detected in plastics in this study, the researchers believe that these compounds may act through multiple mechanisms, and in most cases, these mechanisms are independent of PPARγ and GR. Therefore, more work is needed to clarify the potential mechanisms. The study has some limitations Carroll said the study is the first to look at the lipogenic activity of chemicals extracted from plastic consumer products and is a leading effort in related research. But the researchers say that given the diversity of plastic products and their chemical composition, the samples certainly cannot represent all plastic chemicals that humans are exposed to; given the prevalence and diversity of plastic chemicals, it is also a huge challenge to fully describe all types of plastic chemicals to which humans are exposed. In the study, in order to investigate whether MDC exists in plastic products, the researchers used methanol to extract samples. But this is a relatively extreme case. In reality, it is also worth studying whether MDC in many plastic products will be released. Therefore, while this study demonstrates the presence of potent MDCs in consumer products, it remains to be determined whether they migrate into the air, water or food under realistic conditions, or whether they can be absorbed through the skin. Using the same samples as in this study, researchers have demonstrated that a number of chemicals that cause toxicity in vitro, such as anti-androgenic compounds, migrate into water. However, it is unclear whether this is also true for the MDC involved in this study. In the study, the researchers targeted end products such as plastic packaging for food or personal care products. Since chemical migration is not unidirectional, the possibility that compounds from the contents, such as cosmetics, migrate into the packaging and that these compounds could contribute to adipogenic activity or PPARγ activation cannot be ruled out. Through untargeted chemical analysis, the researchers have tentatively identified several MDCs. However, many compounds remain unidentified, which needs to be addressed by building a more comprehensive spectral database. Related paper information: https://doi.org/10.1021/acs.est.1c06316 China Science Daily (2022-03-01, 2nd edition, original international title: "Beware! Plastic consumer products may cause obesity") Editor | Zhao Lu Typesetting | Zhihai |
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