Very Low Density Lipoprotein Assembly Is Required for cAMP-responsive Element-binding Protein H Processing and Hepatic Apolipoprotein A-IV Expression

Hepatic triglyceride content is highly correlated (r=0.95) with apoA-IV gene expression in mouse models of hepatosteatosis.

• Acute hepatosteatosis induced by fasting or a ketogenic diet resulted in increased hepatic triglyceride content and apoA-IV gene expression.
• Larger triglyceride-enriched VLDL particles were secreted despite a lower rate of triglyceride secretion.
• Inhibition of VLDL particle assembly led to a dramatic increase in hepatic triglyceride content but reduced CREBH processing and apoA-IV expression.
• Restoration of MTP expression in liver-specific MTP knock-out mice proportionately reactivated CREBH processing and apoA-IV expression.
• The results suggest that triglyceride mobilization into the endoplasmic reticulum is necessary for the activation of CREBH processing and apoA-IV gene expression.

AI simplified