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

(TNFα), and could lead to the release of mitochondrial factors that promote apoptosis [149]. Complete cessation of the mitochondrial electron transport and ATP synthesis is caused by extreme depolarisation of mitochondrial membranes, resulting in cellular necrosis [150]. Because damaged mitochondria cannot efficiently metabolise fatty acids, fatty acids accumulate [151], leading to further hepatic lipid accumulation [152], and promoting inflammatory [153] and fibrogenic responses as well as mitogenic responses that could be carcinogenic [154].

Lipotoxicity induces several different types of cellular stresses, including ER stress [154] and impaired autophagy [155]. In addition, it promotes a sterile inflammatory response that can potentiate liver cell injury and death. At the adipocyte level, metabolic dysregulation because of impaired insulin post-receptor signalling leads to excess lipolysis of triglycerides (TGs) and NEFA release into the circulation. At the molecular level, lipotoxicity leads to endoplasmic reticulum (ER) stress, lysosomal dysfunction, inflammasome activation, cell death and activation of inflammatory responses due to lethal and sublethal hepatocellular injury [156].

NASH occurs because lipotoxic hepatocytes release factors that initiate woundhealing responses to replace dying hepatocytes [157]. Wound healing is a complex multifaceted process that can restore the liver structure and function to a healthy state [158].
