TY - JOUR
T1 - Maternal fructose consumption down-regulates Lxra expression via miR-206-mediated regulation
AU - Yamazaki, Mirai
AU - Munetsuna, Eiji
AU - Yamada, Hiroya
AU - Ando, Yoshitaka
AU - Mizuno, Genki
AU - Fujii, Ryosuke
AU - Nouchi, Yuki
AU - Kageyama, Itsuki
AU - Teshigawara, Atsushi
AU - Ishikawa, Hiroaki
AU - Suzuki, Koji
AU - Shimono, Yohei
AU - Hashimoto, Shuji
AU - Ohashi, Koji
PY - 2020/8
Y1 - 2020/8
N2 - Maternal fructose consumption affects the metabolic functions of offspring later in life. However, the molecular mechanism remains poorly understood. Differences of microRNA expression profile and DNA methylation status are a candidate mechanism to explain the developmental programming that contributes to the development of a metabolic disorder. This study examined the transgenerational effect of maternal fructose consumption from the perspective of epigenetic modification. To do this, we collected serum and liver tissues from male offspring rats that were exposed to maternal distilled water or 20% fructose water during gestation and lactation. A decreased serum high-density lipoprotein cholesterol (HDL-C) level was observed in the offspring of fructose-fed dams at postnatal day (PD) 160. Given research indicating a role of liver X receptor alpha (LXRA) in cholesterol metabolism, we analyzed Lxra expression. Real-time polymerase chain reaction analysis demonstrated that offspring that were delivered from fructose-fed dams exhibited decreased Lxra gene expression in their liver tissue. There is a well-established association between Lxra expression and the level of DNA methylation and miR-206 expression. Pyrosequencing assays revealed no differences in the level of DNA methylation in the Lxra promoter region, whereas miR-206 expression was increased in the liver at PD 60 and 160. Our data indicate that early-life exposure to maternal fructose results in changing of miR-206 expression level in the liver that suppresses the expression of Lxra. This phenomenon may be associated with the decreased serum HDL-C level in offspring.
AB - Maternal fructose consumption affects the metabolic functions of offspring later in life. However, the molecular mechanism remains poorly understood. Differences of microRNA expression profile and DNA methylation status are a candidate mechanism to explain the developmental programming that contributes to the development of a metabolic disorder. This study examined the transgenerational effect of maternal fructose consumption from the perspective of epigenetic modification. To do this, we collected serum and liver tissues from male offspring rats that were exposed to maternal distilled water or 20% fructose water during gestation and lactation. A decreased serum high-density lipoprotein cholesterol (HDL-C) level was observed in the offspring of fructose-fed dams at postnatal day (PD) 160. Given research indicating a role of liver X receptor alpha (LXRA) in cholesterol metabolism, we analyzed Lxra expression. Real-time polymerase chain reaction analysis demonstrated that offspring that were delivered from fructose-fed dams exhibited decreased Lxra gene expression in their liver tissue. There is a well-established association between Lxra expression and the level of DNA methylation and miR-206 expression. Pyrosequencing assays revealed no differences in the level of DNA methylation in the Lxra promoter region, whereas miR-206 expression was increased in the liver at PD 60 and 160. Our data indicate that early-life exposure to maternal fructose results in changing of miR-206 expression level in the liver that suppresses the expression of Lxra. This phenomenon may be associated with the decreased serum HDL-C level in offspring.
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U2 - 10.1016/j.jnutbio.2020.108386
DO - 10.1016/j.jnutbio.2020.108386
M3 - Article
C2 - 32388164
AN - SCOPUS:85084199722
VL - 82
JO - Journal of Nutritional Biochemistry
JF - Journal of Nutritional Biochemistry
SN - 0955-2863
M1 - 108386
ER -