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) and pups had higher blood lipids, glucose, and hepatic cholesterol compared with pups from S-fed mothers. Adult C–S offspring demonstrate an atherogenic lipid profile and increased (p < 0.05) hepatic cholesterol and triglyceride content with altered lipid regulatory mRNA expression and protein content compared with S–S offspring. Alternatively, no difference (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.