Rumen Protected Methyl-donors and the Genome: Nutrigenomics and beyond

The importance of methionine as one of the most-limiting amino acids for milk protein synthesis in dairy cows is well-established. Positive effects of peripartal supplementation of methionine (-21 days through +30 days around parturition) also have been observed in terms of milk production. Recent work has revealed that the benefits of rumen-protected methionine (RPM) during the transition period are not only a function of greater voluntary dry matter intake postpartum (Osorio et al., 2013) but also a better immune-metabolic status, i.e. lower concentrations of inflammation markers and better antioxidant capacity (Osorio et al., 2014a). Several of these molecules circulating in the blood are synthesized in the liver, which readily can utilize exogenous methionine to participate in the 1-carbon cycle leading to the synthesis of key intermediates such as S-adenosylmethionine (SAM), phosphatidylcholine (PC), and glutathione (Osorio et al., 2014b). These intermediates play crucial roles in liver lipid metabolism, e.g. PC is essential for synthesis of very-low density lipoproteins (VLDL) which help export triacylglycerol from liver, thus, reducing the likelihood of the cow developing fatty liver and ketosis. The molecule SAM is extremely important as a methyl donor, not only for intermediary metabolites but also for the process of DNA methylation which is a fundamental event occurring in mammalian cells. Methylation of DNA alters gene expression in cells, and is one of the main causes of epigenetic modifications. Therefore, besides its well-established role in milk protein synthesis and liver lipid metabolism, the impact of an optimal level of RPM fed to dairy cattle could have implications at the gene level; not only on the cow but also on the developing calf. The advent and application of genome-enabled technologies such as “transcriptomics” and “metabolomics” along with “bioinformatics” analyses are widely-recognized as tools that have helped advance the knowledge of animal function. Application of these tools is ideal for the study of the effects of RPM on tissue/cell metabolism/function during key life stages of dairy cattle such as the transition period. Nutrigenomics and metabolomics analyses of RPM effects at the tissue level have helped interpret better the physiological responses observed in the cow. Epigenetics analyses of liver tissue and blood neutrophils is ongoing and will add an important layer of mechanistic information on the effects of feeding RPM as it relates to inflammation and oxidative stress. In the longer-term, the aggregation of the various data sets will be valuable for the identification of physiologically-relevant biomarkers in the cow and calf.  

References: 

Supplemental Smartamine M or MetaSmart during the transition period benefits postpartal cow performance and blood neutrophil function. 2013. Osorio JS, Ji P, Drackley JK, Luchini D, Loor JJ. J. Dairy Sci. 96:6248-63. 

Smartamine M and MetaSmart supplementation during the peripartal period alter hepatic expression of gene networks in 1-carbon metabolism, inflammation, oxidative stress, and the growth hormone-insulin-like growth factor 1 axis pathways. 2014. Osorio JS, Ji P, Drackley JK, Luchini D, Loor JJ. J Dairy Sci. Oct. 1. pii: S0022-0302(14)00676-6. doi: 10.3168/jds.2014-8680.

Biomarkers of inflammation, metabolism, and oxidative stress in blood, liver, and milk reveal a better immunometabolic status in peripartal cows supplemented with Smartamine M or MetaSmart. 2014. Osorio JS, Trevisi E, Ji P, Drackley JK, Luchini D, Bertoni G, Loor JJ. J Dairy Sci. 2014 Oct 1. pii: S0022-0302(14)00658-4. doi: 10.3168/jds.2013-7679.