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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\u2010induced transgenerational toxicity by conducting a longitudinal study focusing on hepatic programming prior to disease onset. Impaired Insulin resistance and decreased high\u2010density lipoprotein\u2010cholesterol levels were observed at 160\u00a0days of age. However, metabolic disorders were not observed in 60\u2010day\u2010old offspring. Microarray analysis of 60\u2010day\u2010old offspring livers showed the reduction of hepatic insulin\u2010like growth factor\u20101 (\n                    <jats:italic>Igf1<\/jats:italic>\n                    ) mRNA expression. This reduction continued until the rats were aged 160\u00a0days and attenuated Igf1\u00a0signaling. Hepatic microRNA\u201029 (miR\u201029a) and miR\u2010130a, which target\n                    <jats:italic>Igf1<\/jats:italic>\n                    \u00a0mRNA, 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\n                    <jats:italic>Igf1<\/jats:italic>\n                    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.\n                  <\/jats:p>","DOI":"10.1096\/fj.202101276r","type":"journal-article","created":{"date-parts":[[2021,11,8]],"date-time":"2021-11-08T10:37:15Z","timestamp":1636367835000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Maternal fructose intake predisposes rat offspring to metabolic disorders via abnormal hepatic programming"],"prefix":"10.1096","volume":"35","author":[{"given":"Eiji","family":"Munetsuna","sequence":"first","affiliation":[{"name":"Department of Biochemistry Fujita Health University School of Medicine Toyoake Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroya","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Hygiene Fujita Health University School of 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