FIG. 2.

The role of HB-EGF in the regulation of the hepatic inflammation under overnutrition and obesity. In homeostatic condition, HB-EGF is constitutively expressed in and released from the LSECs for the paracrine EGFR signaling in the hepatocytes for basal VLDL production. The oxidative stress associated with nutrition excess and visceral obesity increased the production of harmful oxidants, including oxidized LDL particles in circulation. The oxidants induce saturation and activation of LSECs and upregulation of HB-EGF expression, which may cause extrahepatic endothelial cell activation and recruitment of bone marrow-derived monocyte recruitment and hepatic VLDL overproduction. The elevation of the circulatory cholesterol induces increased proliferation of the myeloid progenitor in the bone marrow, leading to monocytosis and low-grade inflammation. KC, Kupffer cell; LDL, low-density lipoprotein; LSECs, liver sinusoidal endothelial cells; MoMF, monocyte-derived macrophage; MTP, microsomal triglyceride transfer protein; VLDL, very-low-density lipoprotein. Color images are available online.