Impact of maternal fructose intake on liver stem/progenitor cells in offspring: Insights into developmental origins of health and disease

Life Sci. 2024 Jan 1:336:122315. doi: 10.1016/j.lfs.2023.122315. Epub 2023 Nov 28.

Abstract

Aims: The developmental origin of health and disease (DOHaD) theory postulates that poor nutrition during fetal life increases the risk of disease later in life. Excessive fructose intake has been associated with obesity, diabetes, and nonalcoholic fatty liver disease, and maternal fructose intake during pregnancy has been shown to affect offspring health. In this study, we investigated the effects of high maternal fructose intake on the liver stem/progenitor cells of offspring.

Main method: A fructose-based DOHaD model was established using Sprague-Dawley rats. Small hepatocytes (SHs), which play an important role in liver development and regeneration, were isolated from the offspring of dams that were fed a high-fructose corn syrup (HFCS) diet. The gene expression and DNA methylation patterns were analyzed on postnatal day (PD) 21 and 60.

Key findings: Maternal HFCS intake did not affect body weight or caloric intake, but differences in gene expression and DNA methylation patterns were observed in the SHs of offspring. Functional analysis revealed an association between metabolic processes and ion transport.

Significance: These results suggest that maternal fructose intake affects DNA methylation and gene expression in the liver stem/progenitor cells of offspring. Furthermore, the prolonged retention of these changes in gene expression and DNA methylation in adulthood (PD 60) suggests that maternal fructose intake may exert lifelong effects. These findings provide insights into the DOHaD for liver-related disorders and highlight the importance of maternal nutrition for the health of the next generation.

Keywords: DOHaD; High fructose intake; Maternal diet; Offspring; Small hepatocytes; Stem/progenitor cells.

MeSH terms

  • Animals
  • Female
  • Fructose / adverse effects
  • High Fructose Corn Syrup*
  • Humans
  • Liver / metabolism
  • Maternal Nutritional Physiological Phenomena
  • Obesity / metabolism
  • Pregnancy
  • Prenatal Exposure Delayed Effects* / metabolism
  • Rats
  • Rats, Sprague-Dawley

Substances

  • High Fructose Corn Syrup
  • Fructose