Liver BMAL1/AKT pathway helps protect against alcoholic liver disease in mice by boosting fat metabolism through PPARα

The circadian clock protein BMAL1 is necessary and sufficient to protect mice from alcohol liver disease (ALD).

• Mice lacking BMAL1 in liver cells develop more severe liver fat accumulation and injury when fed an ethanol diet.
• The absence of BMAL1 leads to reduced formation of new fatty acids and impaired breakdown of fatty acids.
• Supplementation with synthetic PPARα ligands can reverse the effects of BMAL1 depletion on liver fat and injury.
• Activating the protein AKT in BMAL1-deficient mice increases fatty acid breakdown and reduces alcohol-induced liver damage.
• Over-expressing the transcription factor ChREBP in BMAL1-deficient mice enhances fatty acid oxidation and partially mitigates liver damage from ethanol.

Simplified