Roman-Garcia Pablo, Quiros-Gonzalez Isabel, Mottram Lynda, Lieben Liesbet, Sharan Kunal, Wangwiwatsin Arporn, Tubio Jose, Lewis Kirsty, Wilkinson Debbie, Santhanam Balaji, Sarper Nazan, Clare Simon, Vassiliou George S, Velagapudi Vidya R, Dougan Gordon, Yadav Vijay K
J Clin Invest. 2014 Jul;124(7):2988-3002. doi: 10.1172/JCI72606. Epub 2014 Jun 9.
Both maternal and offspring-derived factors contribute to lifelong growth and bone mass accrual, although the specific role of maternal deficiencies in the growth and bone mass of offspring is poorly understood. In the present study, we have shown that vitamin B12 (B12) deficiency in a murine genetic model results in severe postweaning growth retardation and osteoporosis, and the severity and time of onset of this phenotype in the offspring depends on the maternal genotype. Using integrated physiological and metabolomic analysis, we determined that B12 deficiency in the offspring decreases liver taurine production and associates with abrogation of a growth hormone/insulin-like growth factor 1 (GH/IGF1) axis. Taurine increased GH-dependent IGF1 synthesis in the liver, which subsequently enhanced osteoblast function, and in B12-deficient offspring, oral administration of taurine rescued their growth retardation and osteoporosis phenotypes. These results identify B12 as an essential vitamin that positively regulates postweaning growth and bone formation through taurine synthesis and suggests potential therapies to increase bone mass.
母体和子代来源的因素都对终身生长和骨量积累有影响,尽管母体缺乏营养对子代生长和骨量的具体作用还知之甚少。在本研究中,我们发现小鼠遗传模型中的维生素B12(B12)缺乏会导致严重的断奶后生长迟缓以及骨质疏松,且子代中该表型的严重程度和发病时间取决于母体基因型。通过综合生理和代谢组学分析,我们确定子代中的B12缺乏会降低肝脏中牛磺酸的产生,并与生长激素/胰岛素样生长因子1(GH/IGF1)轴的废除有关。牛磺酸增加了肝脏中GH依赖的IGF1合成,进而增强了成骨细胞功能,并且在B12缺乏的子代中,口服牛磺酸挽救了它们的生长迟缓和骨质疏松表型。这些结果表明B12是一种必需维生素,它通过牛磺酸合成来正向调节断奶后生长和骨骼形成,并提示了增加骨量的潜在治疗方法。