Endocrine disrupting chemicals in mixture and obesity, diabetes and related metabolic disorders

Abstract

Obesity and associated metabolic disorders represent a major societal challenge in health and quality of life with large psychological consequences in addition to physical disabilities. They are also one of the leading causes of morbidity and mortality. Although, different etiologic factors including excessive food intake and reduced physical activity have been well identified, they cannot explain the kinetics of epidemic evolution of obesity and diabetes with prevalence rates reaching pandemic proportions. Interestingly, convincing data have shown that environmental pollutants, specifically those endowed with endocrine disrupting activities, could contribute to the etiology of these multifactorial metabolic disorders. Within this review, we will recapitulate characteristics of endocrine disruption. We will demonstrate that metabolic disorders could originate from endocrine disruption with a particular focus on convincing data from the literature. Eventually, we will present how handling an original mouse model of chronic exposition to a mixture of pollutants allowed demonstrating that a mixture of pollutants each at doses beyond their active dose could induce substantial deleterious effects on several metabolic end-points. This proof-of-concept study, as well as other studies on mixtures of pollutants, stresses the needs for revisiting the current threshold model used in risk assessment which does not take into account potential effects of mixtures containing pollutants at environmental doses, e.g., the real life exposure. Certainly, more studies are necessary to better determine the nature of the chemicals to which humans are exposed and at which level, and their health impact. As well, research studies on substitute products are essential to identify harmless molecules.

Keywords: Endocrine disrupting chemicals; Persistent organic pollutants; Phthalates; Bisphenol A; Metabolic disorders; Insulin resistance

Core tip: Evidences are accumulating showing that some pollutants endowed with endocrine disrupting activities, the so-called endocrine disrupting chemicals, may contribute to the pandemic evolution of obesity and related metabolic disorders including diabetes. Within this review, we present the concept of endocrine and metabolic disruption and give an overview of the current knowledge of the field, including data from our laboratory and others, specifically focusing on the cocktail effect of pollutants which is one of the biggest concern caused by pollutants nowadays.