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

Abstract

The programming of hepatic lipid dysfunction in response to early cholesterol exposure and the influencing effects of postnatal diet is evaluated in apoE-/- mice. 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. The degree of hepatic lipid deposition observed in adult offspring exposed to excessive early cholesterol is influenced by the postnatal diet.