Endocrine disruptor chemicals as obesogen and diabetogen: Clinical and mechanistic evidence

Abstract

Obesity is becoming an inevitable pandemic all over the world. The World Obesity Federation predicts in the 2022 World Obesity Atlas that one billion people worldwide, including 1 in 5 women and 1 in 7 men, will be living with obesity by 2030. Moreover, the prevalence of diabetes is increasing worldwide, and diabetes is becoming more of a public health problem. Increased insulin resistance due to obesity and deficiency in insulin secretion are the two main causes of type 2 diabetes mellitus (T2DM). An exogenous chemical or mixture of chemicals that interferes with any aspect of hormone action was defined as endocrine-disrupting chemicals (EDCs). Bisphenol A (BPA), the first known EDC, was synthesized and was considered to be estrogenic. Global production of BPA has increased progressively from 5 to 8 million tons (MT) between 2010 and 2016. Furthermore, researchers estimated that the production should reach 10.2 MT by 2022. The human population is exposed to EDCs in daily life in such forms as pesticides/herbicides, industrial and household products, plastics, detergents, and personal care products. The term obesogen was used for chemicals that promote weight gain and obesity by increasing the number of adipocytes and fat storage in existing adipocytes, changing the energy balance, and finally regulating appetite and satiety. Besides the obesogenic effect, EDCs can cause T2DM through alteration in ß cell function and morphology and insulin resistance. In this review, we provide clinical and mechanistic evidence regarding EDCs as obesogen and diabetogen. However, those studies are not enough methodologically to indicate causality. In this respect, randomized clinical trials are needed to investigate the association between obesogen, diabetogen and the related metabolic clinical picture.

Serum Phthalate Concentrations and Biomarkers of Oxidative Stress in Adipose Tissue in a Spanish Adult Cohort

“…Phthalates have been suggested to increase oxidative stress in adipose tissue through activation of proliferator-activated receptors γ (PPARγ). , These are nuclear receptors expressed in the liver that are involved in fatty acid oxidation, body fat accumulation, , as well as in adipogenesis . In fact, phthalates are considered to be obesogenic molecules, i.e., they have the ability to increase the amount of lipids that accumulate in adipose tissue not only at critical stages of development but also later in life . This is an important point to consider, as GraMo is an adult cohort and, although exposure might be more relevant at key developmental stages such as pregnancy and infancy, , long-term adult exposure to low doses of environmental pollutants should also be considered.…”

“… 74 In fact, phthalates are considered to be obesogenic molecules, i.e., they have the ability to increase the amount of lipids that accumulate in adipose tissue not only at critical stages of development but also later in life. 77 This is an important point to consider, as GraMo is an adult cohort and, although exposure might be more relevant at key developmental stages such as pregnancy and infancy, 1 , 78 long-term adult exposure to low doses of environmental pollutants should also be considered.…”

Bisphenol-A (BPA) Exposure as a Risk Factor for Non-Communicable Diseases

“…BPA is an endocrine-disrupting chemical that has been linked to several non-communicable diseases, including obesity, diabetes, cardiovascular disease, reproductive disorders, and cancer [28][29][30]. Epidemiological studies have examined the association between BPA exposure and these diseases, with some providing evidence of positive associations [31,32].…”

An Analysis of the Structural Relationship between Thyroid Hormone-Signaling Disruption and Polybrominated Diphenyl Ethers: Potential Implications for Male Infertility

“…Endocrine-disrupting chemicals (EDCs) are exogenous compounds that interfere with normal functions of the endocrine system, resulting in various endocrine disorders, such as metabolic diseases, neuroendocrine dysfunctions, cancers, reproductive abnormalities, etc. [ 1 , 2 , 3 ]. The adverse effects can occur through EDC actions at multiple stages in an endocrine system, and hence various mechanisms of action have been reported.…”