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 B 12 (B 12 ) 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 B 12 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 B 12 -deficient offspring, oral administration of taurine rescued their growth retardation and osteoporosis phenotypes. These results identify B 12 as an essential vitamin that positively regulates postweaning growth and bone formation through taurine synthesis and suggests potential therapies to increase bone mass.

The effect of Vitamin B12 deficiency on the GH-IGF1 axis

“…Another possible cause is the presence of clinical and laboratory findings of B12 deficiency detected in the F2 mice in the mouse study. In other words, these findings were shown in mice with long-term and much more severe deficiency than the F1 mice, in association with a deficiency that started in the intrauterine period [7]. Since the duration of B12 deficiency in our patients was unknown, this may have affected the lack of significant findings.…”

“…Although recent studies in particular have clearly shown a decrease in bone mineral density in individuals with vitamin B12 deficiency, the underlying mechanism was unknown. In a recent study, Roman-Garcia et al created mutant mice (F1) with gastric intrinsic factor (GIF) deficiency and examined the effect of B12 deficiency on both bone metabolism and growth in their offspring, also with GIF deficiency (F2) [7]. Accordingly, there were low but measurable levels of B12 in the F1 mice, and bone density and growth were unaffected, while undetectable levels of B12, decreased bone density and growth retardation were observed in F2 mice.…”

“…However, its interaction mechanism was unknown until recent years. Roman-Garcia et al showed in an animal study that this effect of taurine is mediated by B12 in the GH postreceptor pathway [7]. Direct taurine deficiency or indirect deficiency due to a decrease in taurine synthesis in the liver in association with B12 deficiency has been shown to reduce IGF-1 (Insulin-like growth factor-1) production by leading to GH resistance.…”

Vitamin B12: Could It Be a Promising Immunotherapy?

“…The second enzymatic reaction requires adenosylcobalamin, which is located in the mitochondria and acts as coenzyme for methylmalonyl-CoA mutase [11,17]. Methylmalonyl-CoA mutase catalyzes conversion of methylmalonyl-CoA to succinyl-CoA (Figure 2), an important metabolite in the Krebs cycle [16] and essential factor for the degradation of odd-chain faty acids.…”

“…IFs represent stomach-speciic glycoproteins secreted by the stomach parietal cells and are essential for the absorption of B12 from the intestinal lumen into the bloodstream [17,21]. Some genetic Immunotherapy -Myths, Reality, Ideas, Futuredefects or pathological changes in gastric and intestinal mucosa may lead to a deiciency of IF, in which case the transport of vitamin B12 is impeded and deiciency is present [17].…”