In Vivo Kinetics of Formate Metabolism in Folate-deficient and Folate-replete Rats

Morrow, Gregory P.; MacMillan, Luke; Lamarre, Simon G.; Young, Sara K.; MacFarlane, Amanda J.; Brosnan, Margaret E.; Brosnan, John T.

doi:10.1074/jbc.m114.600718

Cited by 28 publications

(28 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Investigations of whole-body formate metabolism indicate that there is a significant amount of formate release into the blood ( 22 ). However, the origin of the formate remains largely unconfirmed.…”

Section: Resultsmentioning

confidence: 99%

Serine one-carbon catabolism with formate overflow

et al. 2016

View full text Add to dashboard Cite

show abstract

Section: Resultsmentioning

confidence: 99%

Serine one-carbon catabolism with formate overflow

et al. 2016

View full text Add to dashboard Cite

show abstract

“…In the context of the gut microbiota, we found that abundance of Clostridium cluster I was significantly positively correlated with steatosis score and serum formate, which was also significantly positively correlated with steatosis score, AST, and ALT. Furthermore, serine and glycine, which in the rat are precursors of formate, were also significantly positively correlated with steatosis scores and AST, ALT, or both, as well as members of the gut microbiota, including Enterobacteriaceae abundance, which has also been associated with formate metabolism (73, 74). Increased intestinal lumen formate has been associated with gut microbial dysbiosis, while a serum metabolomics‐based study identified formate as being significantly increased in severe obesity, an effect that was attributed to an altered gut microbiota (73, 75).…”

Section: Discussionmentioning

confidence: 99%

“…In the context of metabolism, formate serves as an important donor of 1‐carbon units that are used for, among others, the synthesis of methyl groups for epigenetic and regulatory methylation reactions and can serve as a shuttle for 1‐carbon units between organs (76). Furthermore, serine is a major source of 1‐carbon groups used in the methyltransferase reaction (74). Lastly, both betaine and dimethylglycine, which are known 1‐carbon donors that circulate throughout the body, were both significantly correlated with insulin AUC, glycine, serine, and each other (74, 76).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, serine is a major source of 1‐carbon groups used in the methyltransferase reaction (74). Lastly, both betaine and dimethylglycine, which are known 1‐carbon donors that circulate throughout the body, were both significantly correlated with insulin AUC, glycine, serine, and each other (74, 76). Altogether, these findings illustrate a clear link between the 1‐carbon (or folate) cycle and hepatic steatosis via alterations in hepatic lipogenesis, lipid export (77), or both.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Maternal prebiotic supplementation reduces fatty liver development in offspring through altered microbial and metabolomic profiles in rats

et al. 2019

View full text Add to dashboard Cite

A maternal high‐fat/sucrose diet, in the presence of maternal obesity, can program increased susceptibility to obesity and metabolic disease in offspring. In particular, nonalcoholic fatty liver disease risk is associated with poor maternal nutrition and obesity status, which may manifest via alterations in gut microbiota. Here, we report that in a preclinical model of diet‐induced maternal obesity, maternal supplementation of a high‐fat/sucrose diet with the prebiotic oligofructose improves glucose tolerance, insulin sensitivity, and hepatic steatosis in offspring following a long‐term high‐fat/sucrose dietary challenge compared with offspring of untreated dams. These improvements are associated with alterations in gut microbial composition and serum inflammatory profiles in early life and improvements in inflammatory and fatty‐acid gene expression profiles in tissues. Serum metabolomics analysis highlights potential metabolic links between the gut microbiota and the degree of steatosis, including alterations in 1‐carbon metabolism. Overall, our data suggest that maternal prebiotic intake protects offspring against hepatic steatosis and insulin resistance following 21 wk of high fat/sucrose diet, which is in part due to alterations in gut microbiota.—Paul, H. A., Collins, K. H., Nicolucci, A. C., Urbanski, S. J., Hart, D. A., Vogel, H. J., Reimer, R. A. Maternal prebiotic supplementation reduces fatty liver development in offspring through altered microbial and metabolomic profiles in rats. FASEB J. 33, 5153–5167 (2019). http://www.fasebj.org

show abstract

“…Interest in the metabolism of formate was generated with the recognition of compartmentalization of folate in the cytosol and mitochondria of most living organisms (Appling; Christiansen). As discussed by Lamarre and colleagues (Morrow et al, 2015, Lamarre et al, 2013), serine, glycine, sarcosine and dimethylglycine are the major donors of the one carbon units to the tetrahydrofolate pool in the mitochondrium. The 5, 10-methylene tetrahydrofolate formed is oxidized through a series of reactions to form formate which can exit the mitochondrium and combine with THF to form 10-formyl-THF.…”

Section: One Carbon Metabolism In Pregnancymentioning

confidence: 96%

One carbon metabolism in pregnancy: Impact on maternal, fetal and neonatal health

Kalhan

2016

Molecular and Cellular Endocrinology

103

View full text Add to dashboard Cite

One carbon metabolism or methyl transfer, a crucial component of metabolism in all cells and tissues, supports the critical function of synthesis of purines, thymidylate and methylation via multiple methyl transferases driven by the ubiquitous methyl donor s-adenosylmethionine. Serine is the primary methyl donor to the one carbon pool. Intracellular folates and methionine metabolism are the critical components of one carbon transfer. Methionine metabolism requires vitamin B12, B6 as cofactors and is modulated by endocrine signals and is responsive to nutrient intake. Perturbations in one carbon transfer can have profound effects on cell proliferation, growth and function. Epidemiological studies in humans and experimental model have established a strong relationship between impaired fetal growth and the immediate and long term consequences to the health of the offspring. It is speculated that during development, maternal environmental and nutrient influences by their effects on one carbon transfer can impact the health of the mother, impair growth and reprogram metabolism of the fetus, and cause long term morbidity in the offspring. The potential for such effects is underscored by the unique responses in methionine metabolism in the human mother during pregnancy, the absence of transsulfuration activity in the fetus, ontogeny of methionine metabolism in the placenta and the unique metabolism of serine and glycine in the fetus. Dietary protein restriction in animals and marginal protein intake in humans causes characteristic changes in one carbon metabolism. The impact of perturbations in one carbon metabolism on the health of the mother during pregnancy, on fetal growth and the neonate are discussed and their possible mechanism explored.

show abstract

In Vivo Kinetics of Formate Metabolism in Folate-deficient and Folate-replete Rats

Cited by 28 publications

References 30 publications

Serine one-carbon catabolism with formate overflow

Serine one-carbon catabolism with formate overflow

Maternal prebiotic supplementation reduces fatty liver development in offspring through altered microbial and metabolomic profiles in rats

One carbon metabolism in pregnancy: Impact on maternal, fetal and neonatal health

Contact Info

Product

Resources

About