Does aflatoxin exposure disrupt hepatic lipid metabolism and lipoprotein processing?

Aflatoxin B1 (AFB1) is a potent hepatotoxin that severely compromises liver function. Research demonstrates that its toxicity is driven by oxidative stress, which initiates a cascade of liver injury and metabolic dysfunction.

Mechanistic pathways of toxicity

• Oxidative stress induction: AFB1 exposure generates reactive oxygen species (ROS) and depletes essential cellular antioxidants, including glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT). This drives lipid peroxidation, as shown by elevated malondialdehyde (MDA) levels.
• Hepatocellular damage: The resulting redox imbalance leads to mitochondrial dysfunction, cell apoptosis, and elevated serum transaminases (ALT and AST). Oxidative damage also triggers inflammatory cascades such as NF-κB activation.
• Endoplasmic reticulum (ER) stress: AFB1 activates ER-stress pathways, including GRP78, ATF6, and IRE1, which further compromises cellular homeostasis.

Impact on lipid and lipoprotein metabolism

• Metabolic disruption: Hepatotoxicity and ER stress dysregulate fatty acid synthesis and oxidation pathways, altering key enzymes like acetyl-CoA carboxylase and shifting the liver toward lipid accumulation and steatosis.
• Impaired lipoprotein assembly: Toxic injury downregulates genes crucial for very-low-density lipoprotein (VLDL) assembly and secretion, including apolipoprotein B (ApoB), microsomal triglyceride transfer protein (MTTP), and apolipoprotein E (ApoE).
• Lipid retention: This disruption prevents the efficient export of triglycerides, causing an accumulation of intrahepatic lipids and oxidized adducts that exacerbates cellular damage.

Bottom line

• Aflatoxin exposure triggers severe oxidative and ER stress that causes hepatocellular injury. This damage directly disrupts hepatic lipid metabolism and impairs the assembly and secretion of ApoB-containing lipoproteins, establishing a damaging cycle of lipid retention and progressive liver injury.