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Excessive early-life cholesterol exposure may have later-life consequences for nonalcoholic fatty liver disease

Published online by Cambridge University Press:  15 April 2020

Jerad H. Dumolt
Affiliation:
Department of Exercise and Nutrition Sciences, School of Public Health and Health Professions, Buffalo, NY, USA14214
Mulchand S. Patel
Affiliation:
Department of Biochemistry, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA14214
Todd C. Rideout*
Affiliation:
Department of Exercise and Nutrition Sciences, School of Public Health and Health Professions, Buffalo, NY, USA14214
*
Address for correspondence: Todd C Rideout, Department of Exercise and Nutrition Sciences, University at Buffalo, Farber Hall G10, Buffalo, NY, 14214, USA. Email: rideout@buffalo.edu.

Abstract

The in utero and immediate postnatal environments are recognized as critical windows of developmental plasticity where offspring are highly susceptible to changes in the maternal metabolic milieu. Maternal hypercholesterolemia (MHC) is a pathological condition characterized by an exaggerated rise in maternal serum cholesterol during pregnancy which can program metabolic dysfunction in offspring, including dysregulation of hepatic lipid metabolism. Although there is currently no established reference range MHC, a loosely defined cutoff point for total cholesterol >280 mg/dL in the third trimester has been suggested. There are several unanswered questions regarding this condition particularly with regard to how the timing of cholesterol exposure influences hepatic lipid dysfunction and the mechanisms through which these adaptations manifest in adulthood. Gestational hypercholesterolemia increased fetal hepatic lipid concentrations and altered lipid regulatory mRNA and protein content. These early changes in hepatic lipid metabolism are evident in the postweaning environment and persist into adulthood. Further, changes to hepatic epigenetic signatures including microRNA (miR) and DNA methylation are observed in utero, at weaning, and are evident in adult offspring. In conclusion, early exposure to cholesterol during critical developmental periods can predispose offspring to the early development of nonalcoholic fatty liver disease (NAFLD) which is characterized by altered regulatory function beginning in utero and persisting throughout the life cycle.

Type
Review
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2020

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