Maternal fructose consumption down-regulates Lxra expression via miR-206-mediated regulation |
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| Affiliation: | 1. School of Environmental Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China;2. Department of Basic Medical Sciences, National Institute for Minamata Disease, Minamata, Kumamoto 867-0008, Japan;1. Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, Akademika Heyrovského 1203/8, Hradec Králové, Czech Republic;2. Czech Academy of Sciences, Institute of Organic Chemistry and Biochemistry, Flemingovo náměstí 542/2, Prague, Czech Republic;1. Department of Clinical Biochemistry, Fujita Health University School of Health Sciences, Toyoake, Japan;2. Department of Joint Research Laboratory of Clinical Medicine, Fujita Health University School of Medicine, Toyoake, Japan;3. Department of Biochemistry, Fujita Health University School of Medicine, Toyoake, Japan;4. Department of Hygiene, Fujita Health University School of Medicine, Toyoake, Japan;5. Department of Public Health, Fujita Health University School of Health Sciences, Toyoake, Japan;1. Department of Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, USA;2. Deparment of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA;3. Department of Obstetrics and Gynecology, University of Michigan Medical School, Ann Arbor, Michigan, USA;4. Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, Michigan, USA;5. Department of Global Health, University of Michigan School of Public Health, Ann Arbor, Michigan, USA;6. Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, USA;7. Department of Pediatrics, University of Michigan Medical School, Ann Arbor, Michigan, USA;1. Department of Biochemical Science and Technology, National Taiwan University, Taipei, Taiwan;2. Institute of Molecular and Cellular Biology, National Taiwan University, Taipei, Taiwan,;3. Department of Biochemistry and Molecular Biology, National Taiwan University College of Medicine, Taipei, Taiwan,;4. Research Center for Development Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan |
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| Abstract: | 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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