Introduction
Obesity is the accumulation of body fat, usually exceeding 20 percent of the body weight. About 600 million adults and 40 million children before age five are known to be obese or overweight globally. Obesity is associated with various factors, such as pathologies, insulin resistance, diabetes, metabolic syndromes, cardiovascular problems, and infertility. Also, at certain doses, endocrine disruptors cause different endocrine functions, such as hormone production, transport, and adverse health effects.
What Are Endocrine Disruptors?
Endocrine disruptors are compounds of exogenous origin whose exposure may occur through placental permeation, breast milk, inhalation, ingestion, transdermal absorption of modifying steroidal hormones, etc. Certain products that act as endocrine disruptors are industrial products, laminators, pesticides, heavy metals, flame retardants, and many plastics of everyday use. The metabolism of endocrine disruptors is low due to their long half-lives. Endocrine disruptors function by mimicking natural hormones. Exposure to environmental disruptors like pesticides during the developmental phase can result in altered gene expression, tissue damage, or other levels of biological problems resulting in permanent dysfunction, an increased chance of obesity, and other chronic conditions such as high sugar levels, metabolic syndrome, heart conditions, various types of cancer, and infertility.
What Is the Role of Endocrine Disruptors in Obesity?
Endocrine disruptors interfere directly or indirectly with obesogens by enhancing adipogenesis (cell differentiation where preadipocytes develop into mature adipocytes) and controlling lipid accumulation or energy balance. Energy balance is achieved by shifting toward calorie storage by changing the basal metabolic rate, altering the microbiota, enhancing food storage, and changing the hormonal control of appetite.
Lipid tissue is a form of connective tissue that consists of precursors and mature adipocytes, endothelial cells, vascular smooth muscle cells, and macrophages. Its primary function is energy storage, where triglyceride adipocyte aggregates are utilized for body response at low temperatures, hunger fasting, or intense muscular exertions. In addition, adipose tissue plays an important role in homeostasis (a self-regulating process for maintaining stability) and acts as a potent biosynthetic machinery to perform endocrine functions. Dysregulation of these pathways results in obesity.
How Do Endocrine Disruptors Cause Obesity?
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Epigenetic Changes Induced by Obesogenic Endocrine Disruptor Chemical Exposure: Endocrine-disrupting chemicals are natural, heterogeneous chemicals or artificial compounds that lead to problems in intact organisms. As endocrine disruptor chemicals bind to receptors, they influence the downstream pattern controlled by each hormone, resulting in a metabolism imbalance. Endocrine disruptor chemicals result in adverse effects even at a low exposure dose. As many endocrine disruptor chemicals are released into the environment by human activities, they contribute to diseases.
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The effects of obesogenic environmental pollutants on adipose tissue are high if exposure to these compounds occurs during prenatal or early childhood. Obesogen targets the transcription regulator, which regulates lipid homeostasis, adipocyte proliferation, and differentiation. Furthermore, because of the lipophilic property, endocrine disruptor chemicals accumulate in adipose tissue. These affect the functions of a group of nuclear hormones called peroxisome proliferator-activated receptors. These are the main targets of obesogenic endocrine disruptor chemicals; PPAR regulates lipid metabolism.
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Bisphenol A (BPA): This artificial compound produces plastics and epoxy resins, including food containers, baby bottles, medical devices, etc. BPA is the most widely produced chemical worldwide. BPA can contaminate food and water due to leaching, leading to many conditions such as diabetes, obesity, polycystic ovarian disease, cardiovascular conditions, thyroid disease, and cancer. BPA interacts with hormone-disrupting chemicals, and these interactions control how genes that respond to estrogen are expressed. For these receptors, the relative binding affinity of BPA is lower than that of estradiol. This receptor is present in the estrogen-related receptor family, is seen in developing embryos and neonates, and could be responsible for some of the effects of BPA during development. As functional endocrine receptors, pancreatic islets, and adipocytes are targeted by BPA. This causes insulin resistance, changes in the way pancreatic beta cells work, liver damage, and obesity. The concentration of BPA in the urine has been associated with a high chance of obesity. A correlation between the urinary BPA level and insulin resistance was seen in obese children. BPA reduces the production and secretion of adiponectin and enhances resistin expression, a condition generally seen in obese people where adiponectin levels are reduced and resistin levels are increased, resulting in insulin resistance.
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Diethylstilbestrol (DES): DES is a synthetic, non-steroidal estrogen that is prescribed to pregnant women to reduce the negative effects of pregnancy outcomes. Studies have shown that exposure to DES during prenatal and perinatal conditions enhances the susceptibility to obesity during growth. Early exposure to DES results in changes in the genetic and epigenetic programming of adipocytes.
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Phthalates: Phthalates are chemicals used to enhance plastic products' flexibility, transparency, and durability. These products are present in many products like children’s toys, footwear, beverage packaging, and medical devices. Human exposure to these chemicals is through dermal contact with polyvinyl chloride and plastic materials, as well as by ingestion and inhalation. Studies in mouse models have shown that phthalate metabolites cause increased metabolic disease and that there is a correlation between phthalates, enhanced adipogenesis, and increased insulin resistance. In addition, recent research has shown a relationship between the urinary excretion of phthalate metabolites and obesity in males and females, and early exposure to these chemicals enhances the risk of weight gain in children.
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Organochlorine and Organophosphate Pesticide: Organochlorine pesticides (OCPs) were widely used and later banned in many countries as these chemicals tend to persist in the environment and bioaccumulate. So OCPs were replaced by organophosphates (OPPs), which are insecticides. In addition, dichlorodiphenyltrichloroethane (DDT) was used widely, accumulating in the fat tissues and acting as an endocrine disruptor. Because of interference in PPARy gene expression and the formation of inflammatory and anti-androgenic cytokines, the presence of these chemicals in adipose tissue may result in obesity and insulin resistance.
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Inhaled Pollutants: These pollutants occur from various sources, such as industrial sources, automobile traffic, natural traffic, and natural disasters like volcanic eruptions or forest fires. Air pollutants are of various types based on their origin, chemical composition, mode of release, and space of release. They are either gaseous or particulate. Obese people are at higher risk of cardiovascular disease after pollutant exposure through inhalation or ingestion. In addition, long-term exposure to pollutants increases the expression of local pro-inflammatory mediators that translocate from the lungs to the circulation, resulting in an enhanced systemic inflammatory response that leads to obesity, a high blood sugar level, resistance to insulin, and metabolic syndrome.
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Flame Retardants: Flame retardants, such as polybrominated diphenyl ether (PBDEs) and polybrominated biphenyls (PBBs), are commonly used by manufacturers of plastics, textiles, surface finishes, and coatings to prevent or delay ignition.
Conclusion
Endocrine disruptors are chemicals that are artificial or synthetic and are used to mimic endocrine hormones. These chemicals alter the functions of the endocrine system. These chemicals increase obesity in adults, and early exposure increases the chances in children. These chemicals are largely used in producing plastics such as bottles, medical equipment, and food containers, as well as industrial pollutants. Exposure can be prevented by the alternative use of these products.
