Figure 4.

Schematic representation of the effects of HCV on steatosis development. HCV may interfere with lipid metabolism via at least three distinct, non-mutually exclusive mechanisms: (i) Impaired secretion. HCV may interfere with the very-low density lipoprotein (VLDL) assembly and/or secretion. Both apolipoprotein B (ApoB) secretion and microsomal triglyceride transfer protein (MTP) activity are impaired by HCV core protein expression. (ii) Increased de novo synthesis of free fatty acids (FFA). HCV has been reported to upregulate sterol regulatory element binding protein (SREBP)-1c signaling pathway, leading to the up-regulation of enzymes involved in lipogenesis such as FA synthase (FAS). (iii) Impaired FA degradation. The HCV core protein reduces the expression of peroxisome proliferators-activated receptor (PPAR)-α, a nuclear receptor regulating several genes responsible for FA degradation, as well as that of mitochondrial carnitine palmitoyltransferase type 1 (CPT)-1, the rate-limiting enzyme of mitochondrial β-oxidation. ACC: acetyl-CoA carboxylase; SCD: stearoyl coenzymeA desaturase. Numbers refer to the bibliographic references.