The Emerging Role of Endocrine Disruptors in Pathogenesis of Insulin Resistance: A Concept Implicating Nonalcoholic Fatty Liver Disease

S.      A. Polyzos; J.      Kountouras; G.      Deretzi; C.      Zavos; C.      S. Mantzoros

Abstract

Endocrine disruptors or endocrine-disrupting chemicals (EDCs) represent a highly heterogeneous group of molecules found in the environment or in consumer products. Toxicology and epidemiology studies have suggested the involvement of diverse EDCs in an increasing number of metabolic disorders, including insulin resistance (IR) and IR-related co morbidities, such as obesity, type 2 diabetes mellitus (T2DM) and polycystic ovary syndrome. Nonalcoholic fatty liver disease (NAFLD), another IR related condition, is emerging as a significant public health concern, affecting 30-45% of the general population in the Western world. To evaluate whether EDCs may also play a role in the pathogenesis of NAFLD, we reviewed the literature on wellstudied EDCs, such as dioxins, bisphenol A, phthalates and other persistent organic pollutants, in relation to pathways that might contribute to the pathogenesis of fatty liver / NAFDL. Certain EDCs may be responsible for inducing alterations similar to those encountered in NAFLD either directly through a hepatotoxic effect and/or indirectly by triggering hepatic and systematic IR. Considering these effects, which act in concert with the effects of the epidemics of obesity and T2DM, EDCs may play a significant role in the pathogenesis of fatty liver, thereby increasing the prevalence of NAFLD worldwide. Translational studies and clinical trials investigating the association between EDCs and NAFLD are required to confirm and extent these studies.

Keywords: Bisphenol A, dioxins, endocrine disruptors, insulin resistance, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, persistent organic pollutants, phthalates, contaminants, xenobiotics, pesticides, fungicides, pharmaceutical agents, phytoestrogens, genistein