Abstract
Non-alcoholic fatty liver disease (NAFLD) is considered the most common liver disorder, affecting around 25% of the population worldwide. It is a complex disease spectrum, closely linked with other conditions such as obesity, insulin resistance, type 2 diabetes mellitus, and metabolic syndrome, which may increase liver-related mortality. In light of this, numerous efforts have been carried out in recent years in order to clarify its pathogenesis and create new prevention strategies. Currently, the essential role of environmental pollutants in NAFLD development is recognized. Particularly, endocrine-disrupting chemicals (EDCs) have a notable influence. EDCs can be classified as natural (phytoestrogens, genistein, and coumestrol) or synthetic, and the latter ones can be further subdivided into industrial (dioxins, polychlorinated biphenyls, and alkylphenols), agricultural (pesticides, insecticides, herbicides, and fungicides), residential (phthalates, polybrominated biphenyls, and bisphenol A), and pharmaceutical (parabens). Several experimental models have proposed a mechanism involving this group of substances with the disruption of hepatic metabolism, which promotes NAFLD. These include an imbalance between lipid influx/efflux in the liver, mitochondrial dysfunction, liver inflammation, and epigenetic reprogramming. It can be concluded that exposure to EDCs might play a crucial role in NAFLD initiation and evolution. However, further investigations supporting these effects in humans are required.
Highlights
Non-alcoholic fatty liver disease (NAFLD) encompasses a broad spectrum of pathologies, ranging from simple steatosis (NAFL) to non-alcoholic steatohepatitis (NASH), with potential progression to cirrhosis and hepatocellular carcinoma (HCC), in individuals without significant alcohol consumption [1,2]
These factors promote the onset of insulin resistance (IR) in adipose tissue, lipolysis and consequent adipocyte dysfunction, increasing influx of free fatty acids (FFAs) into the liver [8,9]. This increase in FFA levels translates into the re-esterification and accumulation of triglycerides (TG) in the liver, simultaneously with the accumulation of other lipid metabolites, such as diacyl-glycerols, long-chain acylcarnitines, and ceramides. These lipotoxic intermediates are responsible for harmful effects such as mitochondrial dysfunction, oxidative stress, and chronic liver inflammation involved in disease progression [8,10,11]
perfluorooctane sulfonate (PFOS) exposition exerts a significant effect in Kupffer cells (KCs) activation with the subsequent release of TNF-α and IL-6 in a JNK and nuclear factor κappa B (NF-κB) activation-dependent mechanism. Increments in these cytokines promote apcn, c-jun, c-myc, and cyd1 increments and, in consequence, hepatocyte proliferation. These findings suggest that PFOS-induced KC activation plays a major role in HCC development [135]
Summary
Non-alcoholic fatty liver disease (NAFLD) encompasses a broad spectrum of pathologies, ranging from simple steatosis (NAFL) to non-alcoholic steatohepatitis (NASH), with potential progression to cirrhosis and hepatocellular carcinoma (HCC), in individuals without significant alcohol consumption [1,2]. This pathology is considered a manifestation of the metabolic syndrome (MetS) due to its association with obesity, insulin resistance (IR), and type 2 diabetes mellitus (T2DM) [3,4]. Contaminated food and water, dust, floor waxes, firefighting foam, electrical wiring, lining of food wrappers, stain resistant carpeting Residential Phenols Bisphenol A
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
