title: Vitamin B₁₂-dependent taurine synthesis regulates growth and bone mass.
abstract: 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.
authors.forename: Pablo
authors.initials: P
authors.lastname: Roman-Garcia
authors.forename: Isabel
authors.initials: I
authors.lastname: Quiros-Gonzalez
authors.forename: Lynda
authors.initials: L
authors.lastname: Mottram
authors.forename: Liesbet
authors.initials: L
authors.lastname: Lieben
authors.forename: Kunal
authors.initials: K
authors.lastname: Sharan
authors.forename: Arporn
authors.initials: A
authors.lastname: Wangwiwatsin
authors.forename: Jose
authors.initials: J
authors.lastname: Tubio
authors.forename: Kirsty
authors.initials: K
authors.lastname: Lewis
authors.forename: Debbie
authors.initials: D
authors.lastname: Wilkinson
authors.forename: Balaji
authors.initials: B
authors.lastname: Santhanam
authors.forename: Nazan
authors.initials: N
authors.lastname: Sarper
authors.forename: Simon
authors.initials: S
authors.lastname: Clare
authors.forename: George S
authors.initials: GS
authors.lastname: Vassiliou
authors.forename: Vidya R
authors.initials: VR
authors.lastname: Velagapudi
authors.forename: Gordon
authors.initials: G
authors.lastname: Dougan
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Yadav
mesh_terms: D000818:Animals; D015519:Bone Density / Q000502:physiology; D001846:Bone Development / Q000502:physiology*; D005260:Female; D006128:Growth / Q000502:physiology*; D006130:Growth Disorders / Q000209:etiology / Q000378:metabolism; D013006:Growth Hormone / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis; D007437:Intrinsic Factor / Q000172:deficiency / Q000235:genetics; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010024:Osteoporosis / Q000209:etiology / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications / Q000235:genetics / Q000378:metabolism; D011297:Prenatal Exposure Delayed Effects; D050799:STAT5 Transcription Factor / Q000378:metabolism; D013654:Taurine / Q000008:administration & dosage / Q000096:biosynthesis*; D014805:Vitamin B 12 / Q000378:metabolism*; D014806:Vitamin B 12 Deficiency / Q000150:complications / Q000235:genetics
chemical_list: D050799:STAT5 Transcription Factor; C519530:insulin-like growth factor-1, mouse; D013654:Taurine; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D007437:Intrinsic Factor; D014805:Vitamin B 12