Postnatal Protein Intake as a Determinant of Skeletal Muscle Structure and Function in Mice-A Pilot Study.

Postnatal Protein Intake as a Determinant of Skeletal Muscle Structure and Function in Mice-A Pilot Study.
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DOI:
10.3390/ijms23158815
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发表时间:
2022-08-08
影响因子:
5.6
通讯作者:
--
中科院分区:
生物学2区
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--
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肌肉减少症的特征是与年龄相关的肌肉纤维数量减少和剩余纤维的额外弱化,导致肌肉质量和功能减少。许多研究将妊娠期和/或哺乳期母亲营养不良与后代骨骼肌稳态改变和肌肉减少症的发展联系起来。本研究的目的是确定是否在后代出生的小鼠母鼠喂养低蛋白饮食在怀孕期间的肌肉骨骼生理学被改变,以及是否有任何生理变化可以调制的营养蛋白质含量在出生后的早期阶段。Thy 1-YFP雌性小鼠自由采食正常(20%)或低蛋白(5%)饲料。将新生幼仔与不同的哺乳期母鼠交叉饲养(维持20%或5%的饮食),以在断奶(21天)时分析三个组:正常至正常(NN)、正常至低(NL)和低至正常(LN)。进一步的后代在哺乳期间自由采食相同的饮食,直到12周龄,创建另外三个组(NNN,NLL,LNN)。出生后低蛋白饮食的小鼠(NL,NLL)表现出持续长达12周的体重和肌肉重量的显著降低,这与仅出生前低蛋白饮食的小鼠(LN,LNN)不同。肌纤维尺寸在NL组而非LN组的小鼠中减小,显示在12周龄时恢复。NLL小鼠的肌力降低,同时伴有NMJ部位的变化以及萎缩相关基因和肌球蛋白基因的变化。此外,12周龄小鼠胫骨的μCT扫描显示了骨量和形态学的变化,导致NLL组的骨量高于对照NNN组。最后,NLL小鼠肌肉中miR-133表达的变化表明这种microRNA在肌肉发育中响应出生后饮食变化的调节作用。总的来说,这些数据表明,小鼠的低母体蛋白质饮食和出生后早期低蛋白质摄入会影响早期骨骼肌的生理和功能,而出生后低蛋白质饮食有利于成年期的骨骼完整性。
Sarcopenia is characterised by an age-related decrease in the number of muscle fibres and additional weakening of the remaining fibres, resulting in a reduction in muscle mass and function. Many studies associate poor maternal nutrition during gestation and/or lactation with altered skeletal muscle homeostasis in the offspring and the development of sarcopenia. The aim of this study was to determine whether the musculoskeletal physiology in offspring born to mouse dams fed a low-protein diet during pregnancy was altered and whether any physiological changes could be modulated by the nutritional protein content in early postnatal stages. Thy1-YFP female mice were fed ad libitum on either a normal (20%) or a low-protein (5%) diet. Newborn pups were cross-fostered to different lactating dams (maintained on a 20% or 5% diet) to generate three groups analysed at weaning (21 days): Normal-to-Normal (NN), Normal-to-Low (NL) and Low-to-Normal (LN). Further offspring were maintained ad libitum on the same diet as during lactation until 12 weeks of age, creating another three groups (NNN, NLL, LNN). Mice on a low protein diet postnatally (NL, NLL) exhibited a significant reduction in body and muscle weight persisting up to 12 weeks, unlike mice on a low protein diet only prenatally (LN, LNN). Muscle fibre size was reduced in mice from the NL but not LN group, showing recovery at 12 weeks of age. Muscle force was reduced in NLL mice, concomitant with changes in the NMJ site and changes in atrophy-related and myosin genes. In addition, μCT scans of mouse tibiae at 12 weeks of age revealed changes in bone mass and morphology, resulting in a higher bone mass in the NLL group than the control NNN group. Finally, changes in the expression of miR-133 in the muscle of NLL mice suggest a regulatory role for this microRNA in muscle development in response to postnatal diet changes. Overall, this data shows that a low maternal protein diet and early postnatal life low-protein intake in mice can impact skeletal muscle physiology and function in early life while postnatal low protein diet favours bone integrity in adulthood.
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