The Role of Endocrine Disruptors Bisphenols and Phthalates in Obesity: Current Evidence, Perspectives and Controversies

Abstract

Excess body weight constitutes one of the major health challenges for societies and healthcare systems worldwide. Besides the type of diet, calorie intake and the lack of physical exercise, recent data have highlighted a possible association between endocrine-disrupting chemicals (EDCs), such as bisphenol A, phthalates and their analogs, and obesity. EDCs represent a heterogeneous group of chemicals that may influence the hormonal regulation of body mass and adipose tissue morphology. Based on the available data from mechanistic, animal and epidemiological studies including meta-analyses, the weight of evidence points towards the contribution of EDCs to the development of obesity, associated disorders and obesity-related adipose tissue dysfunction by (1) impacting adipogenesis; (2) modulating epigenetic pathways during development, enhancing susceptibility to obesity; (3) influencing neuroendocrine signals responsible for appetite and satiety; (4) promoting a proinflammatory milieu in adipose tissue and inducing a state of chronic subclinical inflammation; (5) dysregulating gut microbiome and immune homeostasis; and (6) inducing dysfunction in thermogenic adipose tissue. Critical periods of exposure to obesogenic EDCs are the prenatal, neonatal, pubertal and reproductive periods. Interestingly, EDCs even at low doses may promote epigenetic transgenerational inheritance of adult obesity in subsequent generations. The aim of this review is to summarize the available evidence on the role of obesogenic EDCs, specifically BPA and phthalate plasticizers, in the development of obesity, taking into account in vitro, animal and epidemiologic studies; discuss mechanisms linking EDCs to obesity; analyze the effects of EDCs on obesity in critical chronic periods of exposure; and present interesting perspectives, challenges and preventive measures in this research area.

Cholesterol mediates the effects of single and multiple environmental phenols in urine on obesity

“…The relationship between endocrine disruptors and lipids is very complex. Low concentrations of the same chemicals can increase fat production, whereas high concentrations can inhibit fat cell differentiation [ 63 ]. Reduced safe storage locations of obesity lipophilic chemicals could potentially render them more hazardous in nature compared with agents that induce obesity [ 64 ].…”

“…Patterns of exposure to mixed environmental phenols and the potential effects of mixed exposure on obesity are unknown. BP-3, TCS, MP, and PP are often combined in products, and there was a strong correlation between them ( P -value < 0.05) [ 63 ]. Therefore, analyzing the relationship between mixed environmental phenols and obesity might provide us with a more practical perspective for understanding the synergistic effects of these chemicals.…”