Etiopathogenesis of Nonalcoholic Steatohepatitis: Role of Obesity, Insulin Resistance and Mechanisms of Hepatotoxicity

Figure 2

Reference [74]. FFA may activate several signaling pathways of apoptosis including upregulation and increased number of death receptors such as Fas and TRAIL receptor 5 (DR5), at the level of the plasma membrane, lysosomal permeabilization, and ER stress both coupled to mitochondrial dysfunction resulting in activation of the mitochondrial pathway of apoptosis. These toxic fatty acids may also activate TLR4 signaling resulting in up-regulation of several pro-inflammatory cytokines. Finally, other lipid types such as free cholesterol (FC) and ceramide may induce mitochondrial dysfunction and activate the mitochondrial pathway of apoptosis. Abbreviations: FFA: free fatty acids; SFA: saturated fatty acids. MUFA: monounsaturated fatty acids, FC: free cholesterol, CE. cholesteryl-ester; ER: endoplasmic reticulum.