title: Enhanced Steatosis and Fibrosis in Liver of Adult Offspring Exposed to Maternal High-Fat Diet.
abstract: Early life exposures can increase the risk of developing chronic diseases including nonalcoholic fatty liver disease. Maternal high-fat diet increases susceptibility to development of steatosis in the offspring. We determined the effect of maternal high-fat diet exposure in utero and during lactation on offspring liver histopathology, particularly fibrosis. Female C57Bl/6J mice were fed a control or high-fat diet (HFD) for 8 weeks and bred with lean males. Nursing dams were continued on the same diet with offspring sacrificed during the perinatal period or maintained on either control or high-fat diet for 12 weeks. Increased hepatocyte proliferation and stellate cell activation were observed in the liver of HFD-exposed pups. Offspring exposed to perinatal high-fat diet and high-fat diet postweaning showed extensive hepatosteatosis compared to offspring on high-fat diet after perinatal control diet. Offspring exposed to perinatal high-fat diet and then placed on control diet for 12 weeks developed steatosis and pericellular fibrosis. Importantly, we found that exposure to perinatal high-fat diet unexpectedly promotes more rapid disease progression of nonalcoholic fatty liver disease, with a sustained fibrotic phenotype, only in adult offspring fed a postweaning control diet.
authors.affiliation: Division of Endocrinology, Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Thompson
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Cismowski
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Trask
authors.forename: Scott W
authors.initials: SW
authors.lastname: Lallier
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Graf
authors.forename: Lynette K
authors.initials: LK
authors.lastname: Rogers
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Lucchesi
authors.forename: David R
authors.initials: DR
authors.lastname: Brigstock
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000502:physiology; D059305:Diet, High-Fat / Q000009:adverse effects*; D018450:Disease Progression; D005234:Fatty Liver / Q000209:etiology* / Q000473:pathology; D005260:Female; D005355:Fibrosis / Q000209:etiology* / Q000473:pathology; D022781:Hepatocytes / Q000473:pathology; D007774:Lactation / Q000502:physiology; D008099:Liver / Q000473:pathology*; D008297:Male; D018811:Maternal Exposure; D039382:Maternal Nutritional Physiological Phenomena / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology / Q000473:pathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology* / Q000473:pathology