Adipose Tissue and Endocrine-Disrupting Chemicals: Does Sex Matter?

Abstract

Obesity and metabolic-related diseases, among which diabetes, are prominent public health challenges of the 21st century. It is now well acknowledged that pollutants are a part of the equation, especially endocrine-disrupting chemicals (EDCs) that interfere with the hormonal aspect. The aim of the review is to focus on adipose tissue, a central regulator of energy balance and metabolic homeostasis, and to highlight the significant differences in the endocrine and metabolic aspects of adipose tissue between males and females which likely underlie the differences of the response to exposure to EDCs between the sexes. Moreover, the study also presents an overview of several mechanisms of action by which pollutants could cause adipose tissue dysfunction. Indeed, a better understanding of the mechanism by which environmental chemicals target adipose tissue and cause metabolic disturbances, and how these mechanisms interact and sex specificities are essential for developing mitigating and sex-specific strategies against metabolic diseases of chemical origin. In particular, considering that a scenario without pollutant exposure is not a realistic option in our current societies, attenuating the deleterious effects of exposure to pollutants by acting on the gut-adipose tissue axis may constitute a new direction of research.

Endocrine‐disrupting chemicals and obesity risk: A review of recommendations for obesity prevention policies

“…Expecting individuals to take responsibility for reducing exposure is unlikely to be a sufficient policy response. 48 The second approach from the scientific reviews is to develop clinical treatments for counteracting the effects of EDCs, by reducing the toxic effects or eliminating the EDCs from the body. Susceptible individuals may be identified through genomic testing.…”

Impact of Estrogen Withdrawal and Replacement in Female Mice along the Intestinal Tract. Comparison of E2 Replacement with the Effect of a Mixture of Low Dose Pollutants

“…Adipose tissues, which also express AHR but not PXR and CAR (Ref. in [5]) were investigated and Ahr mRNA levels fluctuated negatively with estrogens in the SAT as observed in the liver, while no significant effect was described in the VAT samples (Figure S2). It indicated that xenobiotic receptors were transcriptionally regulated in a distinct way depending on metabolic tissues.…”

“…According to the World Health Organization [1], there are around 2 billion adults overweight, of those 650 million are considered to be affected by obesity (BMI ≥ 30 kg/m 2 ). Obesity and metabolic diseases reflect an energy imbalance of multifactorial causes, including an environmental origin, according to convincing epidemiological data and experimental studies [2][3][4][5]. Endocrine disruptors are of particular concern since they can interfere with any hormonal action at low doses with non-monotonic dose-response curves [6,7].…”

Genomic and Non-Genomic Actions of Glucocorticoids on Adipose Tissue Lipid Metabolism

“…In contrast, whole-body MR knockout mice have reduced fat mass and body weight [18]. It is estimated that there is sexual dimorphism in MR expression in humans, and its expression could be suppressed by the female biological clock [19]. However, more research is needed to determine how MR expression is affected by sex.…”