Jerad H Dumolt1, Richard W Browne2, Mulchand S Patel3, Todd C Rideout1. 1. Department of Exercise and Nutrition Sciences, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY, 14214, USA. 2. Department of Biotechnical and Clinical Laboratory Sciences, University at Buffalo, Buffalo, NY, 14214, USA. 3. Department of Biochemistry, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, 14214, USA.
Abstract
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.
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.
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