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.

Keywords: adiposity; bisphenol; body mass index; endocrine disruptors; endocrine-disrupting chemicals; obesity; phthalate.

Figure 1

Obesogenic endocrine-disrupting chemicals. Abbreviations: PBDEs: polybrominated diphenyl ethers; PCBs: polychlorinated biphenyls; PFAs: perfluoroalkyl substances. All images are originated from the free medical site http://smart.servier.com/ (accessed on 1 December 2023) by Servier licensed under a Creative Commons Attribution 3.0 Unported License.

Figure 2

Worldwide plastic production in million metric tons and prevalence of excess body weight (BMI: >25 kg/m²) in percentage (%). Figure is based on data from [1,36,37].

Figure 3

Chemical structure of bisphenol A (left) and phthalates (right).

Figure 4

Main mechanisms linking endocrine-disrupting chemicals such as BPA and phthalates to obesity. Abbreviations: AgRP: Agouti-related peptide; α-MSH: α-melanocyte-stimulating hormone; BPA: bisphenol A; C/EBP: CCAAT/enhancer-binding family of proteins; EDCs: endocrine-disrupting chemicals; IL: interleukin; LPS: lipopolysaccharide; MSCs: mesenchymal stem cells; NPY: neuropeptide Y; POMC: proopiomelanocortin; ROS: reactive oxygen species; SCFA: small-chain fatty acid; TNF-α: tumor necrosis factor-α. All images are originated from the free medical site http://smart.servier.com/ (accessed on 1 December 2023) by Servier licensed under a Creative Commons Attribution 3.0 Unported License.