Project description:In dairy cows, administration of high dosages of niacin (NA) was found to cause anti-lipolytic effects, which are mediated by the NA receptor hydroxyl-carboxylic acid receptor 2 (HCAR2) in white adipose tissue (WAT), and thereby to an altered hepatic lipid metabolism. However, almost no attention has been paid to possible direct effects of NA in cattle liver, despite showing that HCAR2 is expressed also in the liver of cattle and is even more abundant than in WAT. Due to this, we hypothesized that feeding of rumen-protected NA to dairy cows influences critical metabolic and/or signaling pathways in the liver through inducing changes in the hepatic transcriptome. In order to identify these pathways, we applied genome-wide transcript profiling in liver biopsies obtained at 1 wk postpartum (p.p.) from dairy cows of a recent study (Zeitz et al., 2018) which were fed a total mixed ration without (control group) or with rumen-protected NA from 21 d before calving until 3 wk p.p. Hepatic transcript profiling revealed that a total of 487 transcripts were differentially expressed [filter criteria fold change (FC) > 1.2 or FC < -1.2 and P < 0.05] in the liver at 1 wk p.p. between cows fed NA and control cows. Substantially more transcripts were down-regulated (n = 338), while only 149 transcripts were up-regulated by NA in the liver of cows. Gene set enrichment analysis (GSEA) for the up-regulated transcripts revealed that the most enriched gene ontology (GO) biological process terms were exclusively related to immune processes, such as leukocyte differentiation, immune system process, leukocyte differentiation, activation of immune response and acute inflammatory response. In line with this, the plasma concentration of the acute phase protein haptoglobin tended to be increased in dairy cows fed rumen-protected NA compared to control cows (P < 0.1). GSEA of the down-regulated transcripts showed that the most enriched biological process terms were related to metabolic processes, such as cellular metabolic process, small molecule metabolic process, lipid catabolic process, organic cyclic compound metabolic process, small molecule biosynthetic process and cellular lipid catabolic process. In conclusion, hepatic transcriptome analysis shows that rumen-protected NA induces genes which are involved mainly in immune processes including acute phase response and stress response in dairy cows at wk 1 p.p. These findings indicate that supplementation of rumen-protected NA to dairy cows in the periparturient period may induce or amplify the systemic inflammation-like condition which is typically observed in the liver of high-yielding dairy cows in the p.p. period.

Project description:BACKGROUND: Lactation is extremely important for dairy cows; however, the understanding of the underlying metabolic mechanisms is very limited. This study was conducted to investigate the inherent metabolic patterns during lactation using the overall biofluid metabolomics and the metabolic differences from non-lactation periods, as determined using partial tissue-metabolomics. We analyzed the metabolomic profiles of four biofluids (rumen fluid, serum, milk and urine) and their relationships in six mid-lactation Holstein cows and compared their mammary gland (MG) metabolomic profiles with those of six non-lactating cows by using gas chromatography-time of flight/mass spectrometry. RESULTS: In total, 33 metabolites were shared among the four biofluids, and 274 metabolites were identified in the MG tissues. The sub-clusters of the hierarchical clustering analysis revealed that the rumen fluid and serum metabolomics profiles were grouped together and highly correlated but were separate from those for milk. Urine had the most different profile compared to the other three biofluids. Creatine was identified as the most different metabolite among the four biofluids (VIP=1.537). Five metabolic pathways, including gluconeogenesis, pyruvate metabolism, the tricarboxylic acid cycle (TCA cycle), glycerolipid metabolism, and aspartate metabolism, showed the most functional enrichment among the four biofluids (false discovery rate<0.05, fold enrichment >2). Clear discriminations were observed in the MG metabolomics profiles between the lactating and non-lactating cows, with 54 metabolites having a significantly higher abundance (P<0.05, VIP>1) in the lactation group. Lactobionic acid, citric acid, orotic acid and oxamide were extracted by the S-plot as potential biomarkers of the metabolic difference between lactation and non-lactation. The TCA cycle, glyoxylate and dicarboxylate metabolism, glutamate metabolism and glycine metabolism were determined to be pathways that were significantly impacted (P<0.01, impact value >0.1) in the lactation group. Among them, the TCA cycle was the most up-regulated pathway (P<0.0001), with 7 of the 10 related metabolites increased in the MG tissues of the lactating cows. CONCLUSIONS: The overall biofluid and MG tissue metabolic mechanisms in the lactating cows were interpreted in this study. Our findings are the first to provide an integrated insight and a better understanding of the metabolic mechanism of lactation, which is beneficial for developing regulated strategies to improve the metabolic status of lactating dairy cows.

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