Maternal high-fat diet programs Wnt genes through histone modification in the liver of neonatal rats.
Maternal high-fat (HF) diets during gestation and lactation have been shown to contribute to metabolic disorders in offspring. Molecular and epigenetic mechanisms underlying this connection may be essential for the prevention and treatment of the fetal origins of metabolic diseases. The current study examined the impact of maternal HF diets on Wnt signaling and histone modification in offspring. Time-pregnant Sprague-Dawley rats were fed either control diet or HF diet during gestation and lactation and then the neonatal offspring of both groups were investigated. The neonatal offspring born to dams fed on HF diets exhibited increases in serum glucose and liver triglyceride levels. Maternal exposure to the HF diet also repressed the mRNA expression of Wnt1 and nuclear β-catenin protein in the liver of offspring. The altered Wnt1 gene expression may be due to the changes of acetylation of H4 at its promoter as well as acetylation of H4 and methylation of H3K9 at coding region. Maternal exposure to the HF diet induced suppression of the Wnt/β-catenin signaling pathway through histone modification, potentially increasing the risk of metabolic syndrome.
Clinical Nutrition Center, Xin Hua Hospital, Shanghai Jiao Tong University, 1665 Kongjiang Road, Shanghai 200092, People's Republic of China.
Ke-feng
KF
Yang
Wei
W
Cai
Jia-li
JL
Xu
Wen
W
Shi
D000107:Acetylation; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight; D059305:Diet, High-Fat; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006657:Histones / Q000378:metabolism*; D007774:Lactation; D008099:Liver / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D039382:Maternal Nutritional Physiological Phenomena; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D051153:Wnt Proteins / Q000235:genetics* / Q000378:metabolism; D051155:Wnt1 Protein / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
C495268:Ctnnb1 protein, rat; D006657:Histones; D051153:Wnt Proteins; D051155:Wnt1 Protein; C495245:Wnt1 protein, rat; D051176:beta Catenin; D008239:Lysine