生命早期钙对后期肥胖发生的影响及骨髓间充质干细胞分化调控机制研究

Many studies have found that the nutritional status in early life can significantly affect the incidence of chronic diseases in adulthood such as obesity. Calcium not only can play its important role on the development of bone, but also can regulate the lipid metabolism, the proliferation and differentiation of preadipocytes. As the development of bone,the proliferation and differentiation of the adipose tissue was also from the differentiation of bone marrow mesenchymal stem cells (BMSCs) . Recently, pregnant women were still in the lack status of calcium, so whether it can affect the development of adipose tissue in the fetal and lay the foundation of the obesity in the adulthood by affecting the differentiation of BMSCs which was in the early part of the fat development. So the correlation between nutritional status of calcium in the pregnancy and the occurrence of obesity in the childhood was discussed by the cohort study. Then the mice which were fed by different concentrations of calcium during pregnancy and lactation were used to verify the effect of calcium intervention on the later obesity which was induced by the high fat diet and discuss the regulation mechanism of BMSCs differentiation on this impact from the morphology and the expression of transcription factors.This project is very significant for the prevention of obesity and the implementation of nutritional intervention in early life.

研究发现，生命早期营养状况会对后期肥胖等多种慢性疾病发生产生重要影响。钙不仅为骨骼发育所必需，同时，在调节脂代谢及前脂肪细胞增殖分化方面也起着重要作用。与骨骼发育一样，脂肪组织细胞增殖分化和聚集也来自骨髓间充质干细胞（BMSCs）的分化。目前我国孕妇钙的摄入量普遍不足，低钙摄入是否会影响脂肪发育的更早期环节--骨髓间充质干细胞（BMSCs）的分化，进而影响胎儿脂肪组织的发育，促进后期肥胖的发生？为此，本项目拟首先采用人群队列研究，观察孕期钙营养状况与学龄前儿童肥胖发生之间的关系；然后利用小鼠实验，在孕期和哺乳期给予不同钙含量饲料喂养，观察其对子代小鼠出生后高脂饲料诱导肥胖发生的影响，进一步从BMSCs分化的形态学及转录因子调控等方面入手，探讨生命早期钙营养状况影响后期肥胖发生的机制。本项目对于肥胖发生的早期营养干预，具有十分重要的意义。

研究发现，生命早期营养状况会对后期肥胖等多种慢性疾病发生产生重要影响。钙不仅为骨骼发育所必需，同时，在调节脂代谢及前脂肪细胞增殖分化方面也起着重要作用。与骨骼发育一样，脂肪组织细胞增殖分化和聚集也来自骨髓间充质干细胞（BMSCs）的分化。目前我国孕妇钙的摄入量普遍不足，低钙摄入是否会影响脂肪发育的更早期环节--骨髓间充质干细胞（BMSCs）的分化，进而影响胎儿脂肪组织的发育，促进后期肥胖的发生？为此，本项目拟首先采用人群队列研究，观察孕期钙营养状况与学龄前儿童肥胖发生之间的关系；然后利用小鼠实验，在孕期和哺乳期给予不同钙含量饲料喂养，观察其对子代小鼠出生后高脂饲料诱导肥胖发生的影响，进一步从BMSCs分化的形态学及转录因子调控等方面入手，探讨生命早期钙营养状况影响后期肥胖发生的机制。结果发现生命早期特别是孕期足量的钙摄入可以更好地促进胎儿生长发育，保证婴儿正常的出生身长及体重，而不良钙营养状况（钙摄入不足或过量）均可加重子代肥胖的发生，其机制可能是通过调控肝脏及性腺脂肪组织中脂代谢相关基因表达，加剧肠道微生物群的失调或影响间充质干细胞的增殖及分化所致。本项目对于肥胖发生的早期营养干预，具有十分重要的意义。