Enhanced steatosis and fibrosis in liver of adult offspring exposed to maternal high-fat diet

Michael D. Thompson, Mary J. Cismowski, Aaron J. Trask, Scott W. Lallier, Amanda E. Graf, Lynette K. Rogers, Pamela A. Lucchesi, David R. Brigstock

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

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 highfat 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.

Original languageEnglish
Pages (from-to)47-59
Number of pages13
JournalGene expression
Volume17
Issue number1
DOIs
StatePublished - 2016

Keywords

  • Developmental origins of disease
  • Fatty liver
  • Fibrosis
  • High-fat diet (HFD)
  • Stellate cell activation

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