Sections of Pediatric Sleep Medicine, Hematology-Oncology, and Pediatric Pulmonology, Department of Pediatrics, Pritzker School of Medicine, Comer Children's Hospital, The University of Chicago, Chicago, IL, USA.
Int J Obes (Lond). 2013 Nov;37(11):1481-9. doi: 10.1038/ijo.2013.12. Epub 2013 Feb 12.
AIMS/HYPOTHESIS: Gestational exposures such as dietary changes can alter offspring phenotype through epigenetic modifications and promote increased risk for specific diseases, such as metabolic syndrome. We hypothesized that high-fat diet (HFD) during late gestation would lead increased risk for insulin resistance and hyperlipidemia via associated epigenetic alterations in tissue adipocytokine genes.
Offspring mice of mothers fed a HFD during late gestation (HFDO) were weighed and their food intake measured weekly till age 20 weeks at which time glucose and insulin tolerance tests, plasma lipid and adipocytokine levels were assessed, as well as mRNA expression in visceral fat. Adipocytokine gene methylation levels in visceral fat, liver and muscle were also assayed.
HFDO mice had increased weight accrual and food intake, and exhibited insulin resistance, hyperlipidemia and hyperleptinemia, as well as hypoadiponectinemia. Furthermore, increased methylation of adiponectin and leptin receptor, and decreased methylation of leptin genes with unchanged glucagon-like peptide-1 methylation patterns emerged in HFDO mice.
Taken together, late gestational HFD induces increased risk of metabolic syndrome in the progeny, which is coupled with hypoadiponectinemia as well as with leptin resistance, and concomitant presence of selective tissue-based epigenetic changes among adipocytokine genes.
目的/假设：孕期饮食等环境暴露因素可通过表观遗传修饰改变后代表型，增加特定疾病（如代谢综合征）的风险。我们假设在妊娠晚期给予高脂肪饮食（HFD）会通过组织脂肪细胞因子基因的相关表观遗传改变，导致胰岛素抵抗和高脂血症的风险增加。
用 HFD 喂养的孕晚期母鼠的后代小鼠（HFDO），每周测量体重和食物摄入量，直至 20 周龄。此时评估葡萄糖和胰岛素耐量试验、血浆脂质和脂肪细胞因子水平，以及内脏脂肪的 mRNA 表达。还检测了内脏脂肪、肝脏和肌肉中脂肪细胞因子基因的甲基化水平。
HFDO 小鼠体重增加和食物摄入增加，表现出胰岛素抵抗、高脂血症和高瘦素血症，以及低脂联素血症。此外，HFDO 小鼠出现了脂联素和瘦素受体基因的甲基化增加，瘦素基因的甲基化减少，而胰高血糖素样肽-1 的甲基化模式不变。
综上所述，妊娠晚期 HFD 会增加后代发生代谢综合征的风险，这与低脂联素血症以及瘦素抵抗有关，同时还伴有脂肪细胞因子基因中存在特定组织的表观遗传变化。
