Hepatic transcript profiling in early-lactation dairy cows fed rumen-protected niacin during the transition from late pregnancy to lactation
Open accessAbstract
In dairy cows, administration of high dosages of niacin (nicotinic acid, NA) was found to cause antilipolytic effects, which are mediated by the NA receptor hydroxyl-carboxylic acid receptor 2 (HCAR2) in white adipose tissue (WAT), and thereby an altered hepatic lipid metabolism. However, almost no attention has been paid to possible direct effects of NA in cattle liver, despite evidence that HCAR2 is also expressed in the liver and is even more abundant than in WAT. Because of this, we hypothesized that feeding a high dosage of rumen-protected NA to dairy cows influences critical metabolic or signaling pathways in the liver by inducing changes in the hepatic transcriptome. To identify these pathways, we applied genome-wide transcript profiling in liver biopsies obtained at d 7 postpartum (p.p.) from dairy cows used in our recent study; cows received either no NA (control group, n = 9) or 79 mg of rumen-protected NA/kg of body weight daily (NA group, n = 9) from 21 d before calving until 3 wk p.p. Hepatic transcript profiling revealed that 487 transcripts were differentially expressed (filter criteria: fold change >1.2 or <-1.2 and P < 0.05) in the liver at d 7 p.p. between cows fed NA and control cows. Substantially more transcripts were downregulated (n = 338), whereas only 149 transcripts were upregulated by NA in the liver of cows. Gene set enrichment analysis for the upregulated transcripts revealed that the most-enriched gene ontology biological process terms were exclusively related to immune processes, such as leukocyte differentiation, immune system process, activation of immune response, and acute inflammatory response. Gene set enrichment analysis of the downregulated 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 showed that rumen-protected NA induces genes that are involved mainly in immune processes, including acute phase response and stress response, in dairy cows at d 7 p.p. Thus, supplementation of a high dosage of rumen-protected NA to dairy cows in the periparturient period may induce or amplify the systemic inflammation-like condition that is typically observed in the liver of high-yielding dairy cows in the p.p. period.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The filter criteria FC > 1.3 and p < 0.05 were used for defining differentially expressed transcripts.
“transcripts with an FC > 1.3 and a Student’s t-test p-value < 0.05 were defined as upregulated, and those with aN FC < −1.3 and a Student’s t-test p-value < 0.05 as downregulated for the comparison OE vs. OC and LE vs. LC.”
From Effect of Ecdysterone on the Hepatic Transcriptome and Lipid Metabolism in Lean and Obese Zucker Rats (2021) · cites this paper as [39]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nature Protocols · doi:10.1038/nprot.2008.211 · Cited by 35,890 · see citing works
Bartel (2004) · doi:10.1016/s0092-8674(04)00045-5 · Cited by 34,714 · see citing works
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkn923 · Cited by 14,108 · see citing works
Gene Expression Omnibus: NCBI gene expression and hybridization array data repository
Edgar, R. (2002) · Nucleic Acids Research · doi:10.1093/nar/30.1.207 · Cited by 13,288 · see citing works
Lewis, B. P., Burge, C. B., & Bartel, D. P. (2005) · Cell · doi:10.1016/j.cell.2004.12.035 · Cited by 11,855 · see citing works
Exploration, normalization, and summaries of high density oligonucleotide array probe level data
Irizarry, R. A. (2003) · Biostatistics · doi:10.1093/biostatistics/4.2.249 · Cited by 10,603 · see citing works
Predicting effective microRNA target sites in mammalian mRNAs
Agarwal, V., Bell, G. W., Nam, J.-W., & Bartel, D. P. (2015) · eLife · doi:10.7554/elife.05005 · Cited by 7,318 · see citing works
A microRNA in a Multiple-Turnover RNAi Enzyme Complex
Hutvágner, G., & Zamore, P. D. (2002) · Science · doi:10.1126/science.1073827 · Cited by 2,081 · see citing works
Hai, T., & Hartman, M. G. (2001) · Gene · doi:10.1016/s0378-1119(01)00551-0 · Cited by 808 · see citing works
PUMA-G and HM74 are receptors for nicotinic acid and mediate its anti-lipolytic effect
Tunaru, S., Kero, J. T., Schaub, A., Wufka, C., Blaukat, A., Pfeffer, K., & Offermanns, S. (2003) · Nature Medicine · doi:10.1038/nm824 · Cited by 794 · see citing works
Hai, T., Wolfgang, C. D., Marsee, D. K., Allen, A. E., & Sivaprasad, U. (1999) · Europe PMC (PubMed Central) · Cited by 629 · see citing works
Nicotinic acid: the broad‐spectrum lipid drug. A 50th anniversary review
Carlson, L. A. (2005) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2005.01528.x · Cited by 586 · see citing works
Acute phase proteins in ruminants
Ceciliani, F., Cerón, J. M. C., Eckersall, P. D., & Sauerwein, H. (2012) · Journal of Proteomics · doi:10.1016/j.jprot.2012.04.004 · Cited by 579 · see citing works
Molecular Identification of High and Low Affinity Receptors for Nicotinic Acid
Wise, A., Foord, S. M., Fraser, N. J., Barnes, A. A., Elshourbagy, N. A., Eilert, M. M., Ignar, D. M., Murdock, P. R., Steplewski, K. M., Green, A. R., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m210695200 · Cited by 540 · see citing works
Invited review: Inflammation during the transition to lactation: New adventures with an old flame
Bradford, B. J., Yuan, K., Farney, J. K., Mamedova, L. K., & Carpenter, A. J. (2015) · Journal of Dairy Science · doi:10.3168/jds.2015-9683 · Cited by 480 · see citing works
Nicotinic Acid: Pharmacological Effects and Mechanisms of Action
Gille, A., Bodor, E. T., Ahmed, K., & Offermanns, S. (2007) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.48.113006.094746 · Cited by 313 · see citing works
Very-low-density lipoprotein assembly and secretion
Shelness, G. S., & Sellers, J. A. (2001) · Current Opinion in Lipidology · doi:10.1097/00041433-200104000-00008 · Cited by 309 · see citing works
Hai, T., Wolford, C. C., & Chang, Y.-S. (2010) · Gene Expression · doi:10.3727/105221610x12819686555015 · Cited by 302 · see citing works
Influence of progesterone on oocyte quality and embryo development in cows
Lonergan, P. (2011) · Theriogenology · doi:10.1016/j.theriogenology.2011.06.012 · Cited by 239 · see citing works
The nicotinic acid receptor GPR109A (HM74A or PUMA-G) as a new therapeutic target
Offermanns, S. (2006) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2006.05.008 · Cited by 179 · see citing works
Erickson, P. S., Murphy, M. R., & Clark, J. H. (1992) · Journal of Dairy Science · doi:10.3168/jds.s0022-0302(92)77852-7 · Cited by 118 · see citing works
Crowley, C., Payne, C. M., Bernstein, H., Bernstein, C., & Roe, D. J. (2000) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4400658 · Cited by 111 · see citing works
Metabolic nuclear receptor signaling and the inflammatory acute phase response
Venteclef, N., Jakobsson, T., Steffensen, K. R., & Treuter, E. (2011) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2011.04.004 · Cited by 99 · see citing works
Effects of encapsulated niacin on metabolism and production of periparturient dairy cows
Morey, S. D., Mamedova, L. K., Anderson, D. E., Armendariz, C. K., Titgemeyer, E. C., & Bradford, B. J. (2011) · Journal of Dairy Science · doi:10.3168/jds.2011-4304 · Cited by 92 · see citing works
Niacin for dairy cattle: a review
Niehoff, I.-D., Hüther, L., & Lebzien, P. (2008) · British Journal Of Nutrition · doi:10.1017/s0007114508043377 · Cited by 85 · see citing works
Pires, J., Pescara, J. B., & Grummer, R. R. (2007) · Journal of Dairy Science · doi:10.3168/jds.2007-0146 · Cited by 84 · see citing works
Yuan, K., SHAVER, R. D., Bertics, S. J., Espineira, M., & Grummer, R. R. (2012) · Journal of Dairy Science · doi:10.3168/jds.2011-5096 · Cited by 79 · see citing works
Oral Nicotinic Acid as a Treatment for Ketosis
Fronk, T. J., & Schultz, L. H. (1979) · Journal of Dairy Science · doi:10.3168/jds.s0022-0302(79)83501-8 · Cited by 78 · see citing works
Bertoli, C., Klier, S., McGowan, C. H., Wittenberg, C., & de Bruin, R. A. M. (2013) · Current Biology · doi:10.1016/j.cub.2013.06.063 · Cited by 75 · see citing works
Wedi, B., Straede, J., Wieland, B., & Kapp, A. (1999) · Blood · doi:10.1182/blood.v94.7.2365.419k08_2365_2373 · Cited by 70 · see citing works
Thiamin and Niacin in the Rumen
Brent, B. E., & Bartley, E. E. (1984) · Journal of Animal Science · doi:10.2527/jas1984.593813x · Cited by 67 · see citing works
Nicotinamide supplementation induces detrimental metabolic and epigenetic changes in developing rats
Li, D., Tian, Y., Guo, J., Sun, W., Lun, Y., Guo, M. H., Luo, N., Cao, Y. Q., Cao, J.-M., Gong, X., et al. (2013) · British Journal Of Nutrition · doi:10.1017/s0007114513001815 · Cited by 65 · see citing works
Ankers, J., Awais, R., Jones, N. A., Boyd, J., Ryan, S., Adamson, A. D., Harper, C. V., Bridge, L., Spiller, D. G., Jackson, D. A., et al. (2016) · eLife · doi:10.7554/elife.10473 · Cited by 62 · see citing works
E2F4 regulates a stable G2 arrest response to genotoxic stress in prostate carcinoma
Crosby, M. E., Jacobberger, J. W., Gupta, D., Macklis, R. M., & Almasan, A. (2006) · Oncogene · doi:10.1038/sj.onc.1209998 · Cited by 60 · see citing works
Pires, J., & Grummer, R. R. (2007) · Journal of Dairy Science · doi:10.3168/jds.2006-904 · Cited by 54 · see citing works
Murray, M. T. (1991) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/0960-0760(91)90320-5 · Cited by 51 · see citing works
Pescara, J. B., Pires, J., & Grummer, R. R. (2010) · Journal of Dairy Science · doi:10.3168/jds.2010-3402 · Cited by 44 · see citing works
An unusual distribution of the niacin receptor in cattle
Titgemeyer, E. C., Mamedova, L. K., Spivey, K. S., Farney, J. K., & Bradford, B. J. (2011) · Journal of Dairy Science · doi:10.3168/jds.2011-4193 · Cited by 41 · see citing works
Gessner, D. K., Winkler, A., Koch, C., Dusel, G., Liebisch, G., Ringseis, R., & Eder, K. (2017) · BMC Genomics · doi:10.1186/s12864-017-3638-1 · Cited by 39 · see citing works
Self-citationMurray, M. T. (1992) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/0960-0760(92)90248-h · Cited by 38 · see citing works
Lemley, C. O., Wilmoth, T. A., Tager, L. R., Krause, K. M., & Wilson, M. E. (2010) · Journal of Dairy Science · doi:10.3168/jds.2009-2539 · Cited by 37 · see citing works
Sun, W., Li, D., Lun, Y., Gong, X., Sun, S., Guo, M., Li-xin, J., Zhang, L.-B., Xiao, F., & Zhou, S. (2011) · Hypertension Research · doi:10.1038/hr.2011.151 · Cited by 34 · see citing works
Bühler, S., Frahm, J., Tienken, R., Kersten, S., Meyer, U., Huber, K., & Dänicke, S. (2017) · Journal of Animal Physiology and Animal Nutrition · doi:10.1111/jpn.12705 · Cited by 25 · see citing works
Bühler, S., Frahm, J., Tienken, R., Kersten, S., Meyer, U., Huber, K., & Dänicke, S. (2016) · Veterinary Immunology and Immunopathology · doi:10.1016/j.vetimm.2016.07.007 · Cited by 17 · see citing works
Niacin in Pharmacological Doses Alters MicroRNA Expression in Skeletal Muscle of Obese Zucker Rats
Couturier, A., Keller, J., Most, E., Ringseis, R., & Eder, K. (2014) · PLoS ONE · doi:10.1371/journal.pone.0098313 · Cited by 15 · see citing works
Self-citationZeitz, J. O., Weber, A., Most, E., Windisch, W. M., Bolduan, C., Geyer, J., Romberg, F.-J., Koch, C., & Eder, K. (2018) · Journal of Dairy Science · doi:10.3168/jds.2018-14490 · Cited by 15 · see citing works
Self-citationExcessive nicotinic acid increases methyl consumption and hydrogen peroxide generation in rats
Li, D., Luo, N., Ma, Q., Li, S., Shi, Q., Cao, Y. Q., & Zhou, S. (2012) · Pharmaceutical Biology · doi:10.3109/13880209.2012.697175 · Cited by 12 · see citing works
Bühler, S., Frahm, J., Liermann, W., Tienken, R., Kersten, S., Meyer, U., Huber, K., & Dänicke, S. (2017) · Research in Veterinary Science · doi:10.1016/j.rvsc.2017.09.012 · Cited by 10 · see citing works
Flagged first, then by citations
1 of the 49 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Kuhla, B. (2020) · animal · doi:10.1017/s1751731119003124 · Cited by 85 · see citing works
Meyer, S., Geßner, D. K., Braune, M. S., Friedhoff, T., Most, E., Höring, M., Liebisch, G., Zorn, H., Eder, K., & Ringseis, R. (2020) · Journal of Animal Science and Biotechnology/Journal of animal science and biotechnology · doi:10.1186/s40104-020-0425-7 · Cited by 77 · see citing works
Self-citationNiacin nutrition and rumen-protected niacin supplementation in dairy cows: an updated review
Chen, J., Yang, Z., & Dong, G. (2019) · British Journal Of Nutrition · doi:10.1017/s0007114519002216 · Cited by 26 · see citing works
Schäfer, L., Grundmann, S. M., Maheshwari, G., Höring, M., Liebisch, G., Most, E., Eder, K., & Ringseis, R. (2023) · Journal of Animal Science and Biotechnology/Journal of animal science and biotechnology · doi:10.1186/s40104-023-00831-6 · Cited by 26 · see citing works
Self-citationBeller, S., Grundmann, S. M., Pies, K., Most, E., Schuchardt, S., Seel, W., Simon, M., Eder, K., & Ringseis, R. (2024) · Poultry Science · doi:10.1016/j.psj.2024.103635 · Cited by 26 · see citing works
Self-citationRingseis, R., Geßner, D. K., Loewenstein, F., Kuehling, J., Becker, S., Willems, H., Lechner, M., Eder, K., & Reiner, G. (2021) · Animals · doi:10.3390/ani11030772 · Cited by 17 · see citing works
Self-citationFibroblast growth factor 21 in dairy cows: current knowledge and potential relevance
Eder, K., Geßner, D. K., & Ringseis, R. (2021) · Journal of Animal Science and Biotechnology/Journal of animal science and biotechnology · doi:10.1186/s40104-021-00621-y · Cited by 17 · see citing works
Self-citationGrundmann, S. M., Ress, K., Zimmermann, L., Höring, M., Liebisch, G., Most, E., Ringseis, R., & Eder, K. (2023) · Nutrients · doi:10.3390/nu15173734 · Cited by 16 · see citing works
Self-citationMarschall, M. J. M., Ringseis, R., Gessner, D. K., Grundmann, S. M., Most, E., Wen, G., Maheshwari, G., Zorn, H., & Eder, K. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22105241 · Cited by 13 · see citing works
Self-citationKuhn, M. J., Mavangira, V., & Sordillo, L. M. (2020) · Journal of Dairy Science · doi:10.3168/jds.2020-18997 · Cited by 14 · see citing works
Powerful detection of polygenic selection and evidence of environmental adaptation in US beef cattlePreprint
Rowan, T. N., Durbin, H. J., Seabury, C. M., Schnabel, R. D., & Decker, J. E. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.03.11.988121 · Cited by 13 · see citing works
Screening for transcriptomic associations with Swine Inflammation and Necrosis Syndrome
Gerhards, K., Becker, S., Kuehling, J., Lechner, M., Willems, H., Ringseis, R., & Reiner, G. (2025) · BMC Veterinary Research · doi:10.1186/s12917-024-04469-y · Cited by 11 · see citing works
Self-citationGaowa, N., Zhang, X., Li, H., Wang, Y., Zhang, J., Hao, Y., Cao, Z., & Li, S. (2021) · Animals · doi:10.3390/ani11030617 · Cited by 9 · see citing works
An, Y., Wang, H., Gao, A., Li, S., Yang, J., Li, B., & Lu, H. (2024) · Animals · doi:10.3390/ani14020182 · Cited by 7 · see citing works
Vatnikov, Y. A., Rudenko, A. A., Gnezdilova, L. A., Sotnikova, E. D., Михайловна, Б. В., Piven, E. A., Kulikov, E. V., Petrov, A., Drukovsky, S. G., & Petrukhina, O. A. (2022) · Veterinary World · doi:10.14202/vetworld.2022.2259-2268 · Cited by 7 · see citing works
Hepatic transcript profiling in beef cattle: Effects of rumen-protected niacin supplementation
Alfaro, G. F., Palombo, V., D’Andrea, M., Cao, W., Zhang, Y., Beever, J. E., Muntifering, R. B., Pacheco, W. J., Rodning, S. P. P., Wang, X., et al. (2023) · PLoS ONE · doi:10.1371/journal.pone.0289409 · Cited by 6 · see citing works
Herrero-Encinas, J., Corrales, N. L., Sevillano, F., Ringseis, R., Eder, K., & Menoyo, D. (2023) · Antioxidants · doi:10.3390/antiox12091751 · Cited by 5 · see citing works
Self-citationSchäfer, L., Grundmann, S. M., Rühl, M., Zorn, H., Seel, W., Simon, M., Schuchardt, S., Most, E., Ringseis, R., & Eder, K. (2024) · Poultry Science · doi:10.1016/j.psj.2024.103975 · Cited by 5 · see citing works
Self-citationRingseis, R., Wächter, S., Cohrs, I., Eder, K., & Grünberg, W. (2024) · Journal of Dairy Science · doi:10.3168/jds.2023-24099 · Cited by 4 · see citing works
Self-citationCarretta, M. D., Creutzburg, P., Borquez, K., Quiroga, J., Alarcón, P., Rivera, A., & Burgos, R. A. (2022) · Developmental & Comparative Immunology · doi:10.1016/j.dci.2022.104562 · Cited by 4 · see citing works
Ringseis, R., Grundmann, S. M., Schuchardt, S., Most, E., & Eder, K. (2021) · Metabolites · doi:10.3390/metabo11090573 · Cited by 4 · see citing works
Self-citationQian, B., Jiang, Z., Chen, R., Yang, T., He, Z., Xie, D., & Fu, W. (2025) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2025.151891 · Cited by 2 · see citing works
Dietary Interventions for Optimal Liver Function in High-Yielding Dairy Cows
Drackley, J. K. (2025) · Annual Review of Animal Biosciences · doi:10.1146/annurev-animal-030424-085431 · Cited by 2 · see citing works
Die Leberverfettung der Milchkuh: Teil 2
Märtens, H. (2023) · Tierärztliche Praxis Ausgabe G Großtiere / Nutztiere · doi:10.1055/a-2178-8847 · Cited by 1 · see citing works
Ma, Q., Tharwat, M., Ullah, A., Liu, J., Alkheraif, A. A., & Khan, M. Z. (2026) · Veterinary Sciences · doi:10.3390/vetsci13101020
- Authors
- Ringseis, R., Zeitz, J. O., Weber, A., Koch, C., & Eder, K.
- Affiliations
- Justus-Liebig-Universität Gießen (DE)
- Lehr- und Versuchsanstalt für Viehhaltung Hofgut Neumühle (DE)
- Corresponding author
- Ringseis, R.
- Venue
- Journal of Dairy Science
- Publisher
- American Dairy Science Association
- Published
- 2019-01
- Volume
- 102
- Issue
- 1
- Pages
- 365-376
- ISSN
- 0022-0302 (ISSN-L)
- OpenAlex
- W2898393148
- Cited by
- 26
- References
- 49
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2023: 5 · 2022: 2 · 2021: 5 · 2020: 5 · 2019: 1
- FWCI
- 4.65
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Dairy Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Life Sciences › Agricultural and Biological Sciences › Agronomy and Crop Science › Reproductive Physiology in Livestock
- Life Sciences › Agricultural and Biological Sciences › Agronomy and Crop Science › Ruminant Nutrition and Digestive Physiology
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Nutrition and Physiology
- Keywords
- nicotinic acid, HCAR2, liver transcriptome, dairy cattle, early lactation, transition period, hepatic gene expression, immune response, acute phase response, systemic inflammation, lipid metabolism, leukocyte differentiation, acute inflammatory response, stress response, gene set enrichment analysis
- MeSH terms
- Acute-Phase Reaction, Animals, Body Weight, Cattle, Diet, Female, Lactation, Lipolysis, Liver, Niacin, Pregnancy, Rumen, Dietary Supplements, Gene Expression Profiling, Postpartum Period
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review