Dissecting the role of cadmium, lead, arsenic, and mercury in non-alcoholic fatty liver disease and non-alcoholic steatohepatitis

The objective of the present study was to review the existing epidemiological and laboratory findings supporting the role of toxic metal exposure in non-alcoholic fatty liver disease (NAFLD). The existing epidemiological studies demonstrate that cadmium (Cd), lead (Pb), arsenic (As), and mercury (Hg) exposure was associated both with an increased risk of NAFLD and altered biochemical markers of liver injury. Laboratory studies demonstrated that metal exposure induces hepatic lipid accumulation resulting from activation of lipogenesis and inhibition of fatty acid β-oxidation due to up-regulation of sterol regulatory element-binding protein 1 (SREBP-1), carbohydrate response element binding protein (ChREBP), peroxisome proliferator-activated receptor γ (PPARγ), and down-regulation of PPARα. Other metabolic pathways involved in this effect may include activation of reactive oxygen species (ROS)/extracellular signal-regulated kinase (ERK) and inhibition of AMP-activated protein kinase (AMPK) signaling. The mechanisms of hepatocyte damage during development of metal-induced hepatic steatosis were shown to involve oxidative stress, endoplasmic reticulum stress, pyroptosis, ferroptosis, and dysregulation of autophagy. Induction of inflammatory response contributing to progression of NAFLD to non-alcoholic steatohepatitis (NASH) upon toxic metal exposure was shown to be mediated by up-regulation of nuclear factor κB (NF-κB) and activation of NRLP3 inflammasome. Moreover, epigen...
Source: Environmental Research - Category: Environmental Health Authors: Source Type: research