Malprogramming of Hepatic Lipid Metabolism due to Excessive Early Cholesterol Exposure in Adult Progeny

SCOPE: The programming of hepatic lipid dysfunction in response to early cholesterol exposure and the influencing effects of postnatal diet is evaluated in apoE⁻/⁻ mice. METHODS AND RESULTS: In two separate studies, female mice are assigned to a standard chow (S) or a cholesterol‐enriched chow (C) diet during gestation and lactation. Male offspring from each dam are weaned on a postnatal S or a hypercaloric western (W) diet resulting in four experimental groups: S–S and C–S (Experiment 1) and S–W and C–W (Experiment 2). At weaning, litters from hypercholesterolemic mothers weighed less (p   0.05) is observed between S–W and C–W in serum and hepatic lipid profiles; however, serum AST and ALT are higher (p < 0.05) in C–W versus S–W offspring. CONCLUSION: The degree of hepatic lipid deposition observed in adult offspring exposed to excessive early cholesterol is influenced by the postnatal diet.