*Regulation of Iron Metabolism in NAFLD/NASH DOI: http://dx.doi.org/10.5772/intechopen.107221*

effects of TNF-α in NASH are enhanced through an abnormal cytokine profile and increased expression of the TNF-α-receptor in the liver [123]. This contributes to additional lipid peroxidation of the mitochondrial membranes, thereby worsening their function and further inducing OS [94]. Adipose tissue shows prominent deregulation of genes related to inflammation in patients with NASH. Induction of NADPH oxidase by TNF-α also leads to inflammation through the expression of TNF receptor-1 and activation of nuclear factor kappa B (NF-κB).

In the pathogenesis of steatohepatitis, hepatic inflammation and fibrogenic progression are pivotal features. Although hepatocyte damage and ROS are regarded to be the initial triggers of inflammation, additional factors such as mitochondrial dysfunction and ER stress have also been implicated as contributory factors in the progression of NAFLD to NASH, by promoting generation of signals and mediators of inflammation.

The association of elevated serum iron values and increased hepatic tissue ferritin deposition with hepatic inflammation and IR in patients with NASH have been well established [94]. In contrast, ROS and lipid peroxidation cause direct damage to hepatocytes by affecting membranes, proteins and DNA [124]. The ensuing damage to nuclear and mtDNA results in necro-inflammation, particularly in the nuclei/cytoplasm of hepatocytes and sinusoidal cells.

The results of current research suggest that hepcidin may dampen inflammatory cytokines through a mechanism that is not well understood. Because excessive inflammation is damaging in many infections, the potential role of hepcidin as a mediator of the innate immune response is a new and unexpected area of study.
