CREB3L3 and hypertriglyceridemia: Blunting CREBH-Insig-2 signaling by siRNA interference against Insig-2 disrupted the inhibitory effect of this signaling pathway on hepatic de novo lipid synthesis, leading to aberrant accumulation of lipid droplets in hepatocytes and systemic hypertriglyceridemia during the nutritional fasting state (Fig. 6).