*Role of the Enzyme Heparanase in the Development of Fatty Liver DOI: http://dx.doi.org/10.5772/intechopen.107530*

when one or more of several mechanisms takes place. Possible mechanisms include excess delivery of free fatty acids (FFAs) to the liver from adipose tissue, increased production of lipids by the liver (De novo lipogenesis), decreased oxidation of fatty acids within the hepatocytes, and impaired export of the TG-rich v-LDL particles. Accumulation of fat droplets in hepatocytes results in cell ballooning and derangement of the normal structure of the liver, and thus induces activation of inflammatory reaction, with activation of HSCs and KCs, which are both involved in the initiation of inflammatory and fibrogenic responses, then leading to the release of proinflammatory cytokines, chemokines, and growth factors, that further augment the inflammatory process and result in activation of HSCs. Of the cytokines released by KCs, tumor growth factor-β (TGF-β), which induces fibrogenesis through activation of HSCs and reactive oxygen substances, leading to accelerated inflammation and progressive liver damage [39], where KCs release also the proinflammatory cytokines TNF-α, IL-6, and IL-β, which also contribute to liver damage. Moreover, following liver insult, both KCs and hepatocytes secrete fibroblast growth factor 2 (FGF-2), which stimulates hepatocyte regeneration and growth, as well as the proliferation and activation of HSCs. Higher levels of FGF-2 result in excess ECM deposition by HSCs, and induce hepatic tissue perturbation and disruption [40, 41]. Upon activation, HSCs transform to α-SMA positive myofibroblasts, which secrete large amounts of ECM proteins causing profound alteration of the extracellular micro-environment. As these processes aim to repair damaged liver tissue, prolonged injury to the liver together with prolonged activation of the repair system result in degradation of the regeneration process, and in late stages may result in uncontrolled fibrogenesis, excess ECM accumulation, and disruption of liver structure [42–45]. Indeed, liver tissue repair is also supported by autophagy, a process by which cells degrade their own components by forming autophagosomes and autolysosomes, and in the liver, autophagy is expected in normal circumstances to result in decreased liver fibrosis [46, 47].
