Maternal fructose intake predisposes rat offspring to metabolic disorders via abnormal hepatic programming

Eiji Munetsuna, Hiroya Yamada, Mirai Yamazaki, Yoshitaka Ando, Genki Mizuno, Yuji Hattori, Itsuki Kageyama, Atsushi Teshigawara, Yuki Nouchi, Hiroaki Ishikawa, Ryosuke Fujii, Yoshiji Ohta, Koji Suzuki, Yohei Shimono, Koji Ohashi, Shuji Hashimoto

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10 Citations (Scopus)


Given that fructose consumption has increased by more than 10-fold in recent decades, it is possible that excess maternal fructose consumption causes harmful effects in the next generation. This study attempted to elucidate the mechanism of the harmful effects of excessive maternal fructose intake from the perspective of offspring liver function. Female rats during gestation and lactation were fed water containing fructose, and their offspring were fed normal water. We attempted to elucidate the mechanism of fructose-induced transgenerational toxicity by conducting a longitudinal study focusing on hepatic programming prior to disease onset. Impaired Insulin resistance and decreased high-density lipoprotein-cholesterol levels were observed at 160 days of age. However, metabolic disorders were not observed in 60-day-old offspring. Microarray analysis of 60-day-old offspring livers showed the reduction of hepatic insulin-like growth factor-1 (Igf1) mRNA expression. This reduction continued until the rats were aged 160 days and attenuated Igf1 signaling. Hepatic microRNA-29 (miR-29a) and miR-130a, which target Igf1 mRNA, were also found to be upregulated. Interestingly, these miRNAs were upregulated in the absence of metabolic disorder. In this study, we found that maternal fructose intake resulted in dysregulated expression of Igf1 and its target miRNAs in the offspring liver, and that these offspring were more likely to develop metabolic disorders. Abnormal hepatic programming induced by an imbalanced maternal nutritional environment is maintained throughout life, implying that it may contribute to metabolic disorders.

Original languageEnglish
Article numbere22030
JournalFASEB Journal
Issue number12
Publication statusPublished - 12-2021

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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