Lipids in Liver Disease: Looking Beyond Steatosis

Increased HSC activation by dietary cholesterol. Increased dietary cholesterol up-regulates TLR4 protein levels in HSCs, which in turn down-regulates the inhibitory TGF-β pseudoreceptor Bambi. The resulting increase in TGF-β signaling promotes increased HSC activation and liver fibrosis.

Hydrolysis of triglyceride in hepatic lipid droplets yields toxic fatty acids, which can activate an injurious positive feedback loop by activating PPAR-α and stimulating triglyceride lipase(s). NorUDCA, PPAR-α inhibition, and high-fat feeding can each interrupt the cycle by preventing further hydrolysis and shifting equilibrium in the hepatocyte toward triglyceride synthesis and storage.