TY - JOUR
T1 - Maternal high-fructose corn syrup consumption causes insulin resistance and hyperlipidemia in offspring via DNA methylation of the Pparα promoter region
AU - Ando, Yoshitaka
AU - Yamada, Hiroya
AU - Munetsuna, Eiji
AU - Yamazaki, Mirai
AU - Kageyama, Itsuki
AU - Teshigawara, Atsushi
AU - Nouchi, Yuki
AU - Fujii, Ryosuke
AU - Mizuno, Genki
AU - Sadamoto, Nao
AU - Ishikawa, Hiroaki
AU - Suzuki, Koji
AU - Hashimoto, Shuji
AU - Ohashi, Koji
N1 - Funding Information:
This work was supported by the Ministry of Education, Culture, Sports, Science , and Technology of Japan via a Grant-in- Aid for Scientific Research and Grant-in-Aid, 2020-2023 (No. 20H04134 ).
Publisher Copyright:
© 2022
PY - 2022/5
Y1 - 2022/5
N2 - There are concerns about the negative effects of fructose intake during pregnancy on the next generation. We have previously reported that offspring from dams fed with fructose during gestation and lactation demonstrate abnormal lipid metabolism in the liver. In this study, we aimed to elucidate the molecular mechanism of the effects of maternal high-fructose corn syrup (HFCS) consumption on offspring. Pregnant Sprague-Dawley rats were fed with 20% HFCS water solution during gestation and lactation. Offspring were put on a normal diet after weaning, and the serum parameters and gene expression patterns were studied at predetermined intervals. Offsprings from pregnant rats fed with 20% HFCS (HFCS group) developed insulin resistance and hyperlipidemia at 60 d of age. RNA-seq analysis demonstrated that peroxisome proliferator-activated receptor α (PPARα) expression is downregulated by maternal HFCS intake. Hepatic Pparα expression in the HFCS group appeared to be suppressed by the enhanced DNA methylation of its promoter region. It is suggested that the development of insulin resistance and hyperlipidemia in the HFCS group may be attributable to aberrant Pparα methylation in the offspring liver. Pparα hypermethylation may be one of molecular mechanism underlying the toxicity of maternal fructose intake.
AB - There are concerns about the negative effects of fructose intake during pregnancy on the next generation. We have previously reported that offspring from dams fed with fructose during gestation and lactation demonstrate abnormal lipid metabolism in the liver. In this study, we aimed to elucidate the molecular mechanism of the effects of maternal high-fructose corn syrup (HFCS) consumption on offspring. Pregnant Sprague-Dawley rats were fed with 20% HFCS water solution during gestation and lactation. Offspring were put on a normal diet after weaning, and the serum parameters and gene expression patterns were studied at predetermined intervals. Offsprings from pregnant rats fed with 20% HFCS (HFCS group) developed insulin resistance and hyperlipidemia at 60 d of age. RNA-seq analysis demonstrated that peroxisome proliferator-activated receptor α (PPARα) expression is downregulated by maternal HFCS intake. Hepatic Pparα expression in the HFCS group appeared to be suppressed by the enhanced DNA methylation of its promoter region. It is suggested that the development of insulin resistance and hyperlipidemia in the HFCS group may be attributable to aberrant Pparα methylation in the offspring liver. Pparα hypermethylation may be one of molecular mechanism underlying the toxicity of maternal fructose intake.
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U2 - 10.1016/j.jnutbio.2022.108951
DO - 10.1016/j.jnutbio.2022.108951
M3 - Article
C2 - 35123000
AN - SCOPUS:85125172968
SN - 0955-2863
VL - 103
JO - Nutrition Reports International
JF - Nutrition Reports International
M1 - 108951
ER -