Low protein intake compromises the recovery of lactation-induced bone loss in female mouse dams without affecting skeletal muscles
Low protein intake compromises the recovery of lactation-induced bone loss in female mouse dams without affecting skeletal muscles
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DOI：
10.1101/2020.05.02.073759
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发表时间：
2020-05
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影响因子：
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通讯作者：
I. Kanakis;Moussira Alameddine;M. Scalabrin;R. J. van ‘t Hof;T. Liloglou;S. Ozanne;K. Goljanek‐Whysall;A. Vasilaki
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文献类型：
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作者：
I. Kanakis;Moussira Alameddine;M. Scalabrin;R. J. van ‘t Hof;T. Liloglou;S. Ozanne;K. Goljanek‐Whysall;A. Vasilaki
哺乳导致的骨丢失是由于胎儿生长对钙的高需求造成的，但骨骼恢复通常在断奶后迅速实现。饮食蛋白质对胎儿和母亲至关重要，但蛋白质营养不良对母亲骨骼和骨骼肌的影响在很大程度上是未知的。在孕期和哺乳期饲喂正常(N，20%)或低蛋白(L，8%)饲料的小鼠，在哺乳后28d的骨骼恢复期内保持相同的饲料(NN，LL)或从低蛋白转换为正常(LN)。骨骼肌形态和神经肌肉连接的完整性在任何一组之间都没有不同。然而，饲喂低蛋白饲料的母猪在哺乳期结束时表现出广泛的骨丢失，随后NN母猪的骨骼完全恢复，LN母猪的部分恢复，而LL母猪的骨恢复较差。低蛋白饲料组小鼠原代成骨细胞体外成骨减少，成骨标志物基因表达降低，焦磷酸测序分析显示BMPR1a、ptch1、Sirt1、OSX和Igf1r基因启动子甲基化无差异，而miR-26a、-34a和-125b基因表达发生改变。因此，正常的蛋白质饮食对于母亲生殖期间的肌肉骨骼健康是不可或缺的。
Lactation-induced bone loss occurs due to high calcium requirements for fetal growth but skeletal recovery is normally achieved promptly post-weaning. Dietary protein is vital for fetus and mother but the effects of protein undernutrition on the maternal skeleton and skeletal muscles is largely unknown. We used mouse dams fed with normal (N, 20%) or low (L, 8%) protein diet during gestation and lactation and maintained on the same diets (NN, LL) or switched from low to normal (LN) during a 28d skeletal restoration period post lactation. Skeletal muscle morphology and neuromuscular junction integrity was not different between any of the groups. However, dams fed the low protein diet showed extensive bone loss by the end of lactation, followed by full skeletal recovery in NN dams, partial recovery in LN and poor bone recovery in LL dams. Primary osteoblasts from low protein diet fed mice showed decreased in vitro bone formation and decreased osteogenic marker gene expression; promoter methylation analysis by pyrosequencing showed no differences in Bmpr1a, Ptch1, Sirt1, Osx and Igf1r osteoregulators, while miR-26a, -34a and -125b expression was found altered in low protein fed mice. Therefore, normal protein diet is indispensable for maternal musculoskeletal health during the reproductive period.