Enhanced Steatosis and Fibrosis in Liver of Adult Offspring Exposed to Maternal High-Fat Diet

Gene Expr. 2016;17(1):47-59. doi: 10.3727/105221616X692135. Epub 2016 Jun 23.

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.

MeSH terms

  • Animals
  • Cell Proliferation / physiology
  • Diet, High-Fat / adverse effects*
  • Disease Progression
  • Fatty Liver / etiology*
  • Fatty Liver / pathology
  • Female
  • Fibrosis / etiology*
  • Fibrosis / pathology
  • Hepatocytes / pathology
  • Lactation / physiology
  • Liver / pathology*
  • Male
  • Maternal Exposure
  • Maternal Nutritional Physiological Phenomena / physiology
  • Mice
  • Mice, Inbred C57BL
  • Non-alcoholic Fatty Liver Disease / etiology
  • Non-alcoholic Fatty Liver Disease / pathology
  • Pregnancy
  • Prenatal Exposure Delayed Effects / etiology*
  • Prenatal Exposure Delayed Effects / pathology