Laboratory of Nutrition and Development, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China.
Animal Laboratory Center, First Affiliated Hospital of PLA General Hospital., Beijing 100037, China.
Nutr Res. 2019 May;65:29-42. doi: 10.1016/j.nutres.2019.01.006. Epub 2019 Jan 28.
Disturbed calcium homeostasis has detrimental effects on brain development and function, particularly in early life because of epigenetic determination of early nutrition on later health. We hypothesized that the imbalance of calcium status in early life might have long-lasting effects on brain DHA accretion though epigenetic modification on fatty acid desaturases (Fads). Three to four week old C57BL/6J female mice were fed 3 reproductive diets with different calcium concentrations - low (LC, 0.25%), normal (NC, 0.70%) and high-calcium (HC, 1.20%) respectively throughout pregnancy and lactation. Maternal LC diet reduced tissue (brain and hepatic) DHA concentrations in both male and female offsprings at postnatal 21 day, with reductions in male instead of female offsprings in adulthood. Maternal HC diet only reduced hepatic DHA concentration in adult male offsprings. Furthermore, maternal LC diet reduced hepatic but increased brain expressions of Fads1 or Fads2 in 21-days old offsprings, with similar changes in adult male instead of female offsprings. Maternal HC diet reduced hepatic or brain expressions of Fads1 or Fads2 in 21-days old offsprings, and only reduced Fads2 in the liver with adult male offsprings. Determination of DNA methylation (CpG4, CpG5, CpG7,8, CpG14-17 and CpG19) showed that maternal LC diet caused hypermethylation of Fads2 promoter in the liver and hypomethylation in the brain in 21-days old offsprings, as well as in adult male offsprings. These data demonstrate that the imbalance of calcium intake in early life might have long-term gender-specific effects on brain accretion of DHA mediated by altered DNA methylation and associated expressions of Fads.
钙稳态失衡对大脑发育和功能有不利影响，尤其是在生命早期，因为早期营养的表观遗传决定了后期的健康。我们假设，生命早期钙状态的失衡可能通过脂肪酸去饱和酶（Fads）的表观遗传修饰对脑 DHA 积累产生长期影响。3 至 4 周龄 C57BL/6J 雌性小鼠在整个妊娠期和哺乳期分别喂食 3 种不同钙浓度的生殖饮食——低钙（LC，0.25%）、正常钙（NC，0.70%）和高钙（HC，1.20%）。母体 LC 饮食降低了雄性和雌性后代组织（大脑和肝脏）中 DHA 的浓度，在成年时雄性后代的减少而不是雌性后代的减少。母体 HC 饮食仅降低了成年雄性后代肝脏中的 DHA 浓度。此外，母体 LC 饮食降低了 21 天大的后代肝脏中的 Fads1 或 Fads2 的表达，但在成年雄性后代中则降低了 Fads2 的表达。母体 HC 饮食降低了 21 天大的后代肝脏或大脑中 Fads1 或 Fads2 的表达，仅降低了成年雄性后代肝脏中的 Fads2。DNA 甲基化（CpG4、CpG5、CpG7、8、CpG14-17 和 CpG19）的测定表明，母体 LC 饮食导致 21 天大的后代肝脏中 Fads2 启动子的过度甲基化和大脑中的低甲基化，以及成年雄性后代的 Fads2 启动子的过度甲基化和大脑中的低甲基化。这些数据表明，生命早期钙摄入的失衡可能通过改变 DNA 甲基化和相关的 Fads 表达，对脑 DHA 的积累产生长期的性别特异性影响。
