{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T03:12:17Z","timestamp":1791947537340,"version":"4.3.4"},"reference-count":35,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T00:00:00Z","timestamp":1731456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hebei Province Key Research and Development Plan Project","award":["22326616D"],"award-info":[{"award-number":["22326616D"]}]},{"name":"Hebei Province Key Research and Development Plan Project","award":["BJK2024001"],"award-info":[{"award-number":["BJK2024001"]}]},{"name":"Science Research Project of Hebei Education Department","award":["22326616D"],"award-info":[{"award-number":["22326616D"]}]},{"name":"Science Research Project of Hebei Education Department","award":["BJK2024001"],"award-info":[{"award-number":["BJK2024001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>This study aimed to explore the effects of sodium butyrate on liver metabolism in goats subjected to a high-concentrate diet. We randomly assigned twelve Saanen-lactating goats into two groups, one of which received a high-concentrate diet (concentrate: forage = 60:40, control group), while the other received the same basal diet supplemented with sodium butyrate (SB) (10 g\/kg basal diet, SB group). Compared with the control diet, the SB diet considerably increased the milk fat percentage and content (p &lt; 0.05), with an increase of 0.67% in the milk fat content of the SB group. By employing a global metabolomics approach based on ultra-performance liquid chromatography\u2013tandem mass spectrometry (UPLC\u2013MS\/MS), we identified 6748 ions in ESI+ mode and 3573 ions in ESI\u2212 mode after liver isolation from both groups. A total of twenty-three metabolites, including phospholipids, fatty acids, and ribose phosphate, were found to be dysregulated according to a search against the human metabolome database (HMDB). Pathway analysis revealed activation of the pentose phosphate pathway, glycerophospholipid metabolism, and unsaturated fatty acid synthesis. The SB diet also modulated the expression of key lipogenic enzymes, such as acetyl-CoA carboxylase (ACC) and stearoyl-CoA desaturase (SCD-1), which are downstream targets of the transcription factor sterol regulatory element-binding proteins-1c (SREBP-1c), inducing a significant upregulation (p &lt; 0.05). Furthermore, 6-phosphogluconate dehydrogenase (6PGDH) levels in the liver were elevated after the lactating goats were fed the SB diet (p &lt; 0.05). Our study reveals that the SB diet may offer substantial benefits in enhancing the milk quality of subacute ruminal acidosis (SARA) goats. This is accomplished by augmenting the activity of the liver pentose phosphate pathway and the process of de novo fatty acid synthesis in lactating goats.<\/jats:p>","DOI":"10.3390\/ani14223249","type":"journal-article","created":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T06:10:48Z","timestamp":1731478248000},"page":"3249","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Metabolomics Reveals the Mechanism by Which Sodium Butyrate Promotes the Liver Pentose Phosphate Pathway and Fatty Acid Synthesis in Lactating Goats"],"prefix":"10.3390","volume":"14","author":[{"given":"Lin","family":"Li","sequence":"first","affiliation":[{"name":"School of Chemical Engineering and Biotechnology, Xingtai University, Xingtai 054001, China"},{"name":"Key Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture, Nanjing Agricultural University, Nanjing 210095, China"},{"name":"Hebei Key Laboratory of Digital Freshwater Aquaculture Technology, Xingtai University, Xingtai 054001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuping","family":"Yan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanshu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1080\/10495398.2020.1806073","article-title":"Long-term high-concentrate diet feeding induces apoptosis of rumen epithelial cells and inflammation of rumen epithelium in dairy cows","volume":"33","author":"Dai","year":"2022","journal-title":"Anim. Biotechnol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2487","DOI":"10.3168\/jds.2022-22509","article-title":"Relationship between farm management strategies, reticuloruminal pH variations, and risks of subacute ruminal acidosis","volume":"106","author":"Huot","year":"2023","journal-title":"J. Dairy Sci."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Mikulak, J., Bruni, E., Oriolo, F., Vito, C.D., and Mavilio, D. (2019). Hepatic Natural Killer Cells: Organ-Specific Sentinels of Liver Immune Homeostasis and Physiopathology. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00946"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Chang, G., Zhang, K., Xu, T., Jin, D., Seyfert, H.M., Shen, X., and Zhuang, S. (2015). Feeding a high-grain diet reduces the percentage of LPS clearance and enhances immune gene expression in goat liver. BMC Vet. Res., 11.","DOI":"10.1186\/s12917-015-0376-y"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1017\/S1751731116001701","article-title":"Changes in milk performance and hepatic metabolism in mid-lactating dairy goats after being fed a high concentrate diet for 10 weeks","volume":"11","author":"Dong","year":"2017","journal-title":"Animal"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Li, L., Cao, Y., Xie, Z., and Zhang, Y. (2017). A high-concentrate diet induced milk fat decline via glucagon-mediated activation of AMP-activated protein kinase in dairy cows. Sci. Rep., 7.","DOI":"10.1038\/srep44217"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Dong, H., Wang, S., Jia, Y., Ni, Y., Zhang, Y., Zhuang, S., Shen, X., and Zhao, R. (2013). Long-term effects of subacute ruminal acidosis (SARA) on milk quality and hepatic gene expression in lactating goats fed a high-concentrate diet. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0082850"},{"key":"ref_8","first-page":"3745135","article-title":"Sodium butyrate ameliorates oxidative stress-induced intestinal epithelium barrier injury and mitochondrial damage through AMPK-mitophagy pathway","volume":"2022","author":"Li","year":"2022","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.ebiom.2018.03.030","article-title":"Sodium butyrate inhibits inflammation and maintains epithelium barrier integrity in a TNBS-induced inflammatory bowel disease mice model","volume":"30","author":"Chen","year":"2018","journal-title":"EBioMedicine"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1111\/jpn.13571","article-title":"Effect of sodium butyrate on slaughter performance, serum indexes and intestinal barrier of rabbits","volume":"106","author":"Li","year":"2022","journal-title":"J. Anim. Physiol. Anim. Nutr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"6259381","DOI":"10.1155\/2021\/6259381","article-title":"Sodium butyrate alleviates intestinal inflammation in mice with necrotizing enterocolitis","volume":"2021","author":"Sun","year":"2021","journal-title":"Mediat. Inflamm."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.3168\/jds.2022-22224","article-title":"Complementary hepatic metabolomics and proteomics reveal the adaptive mechanisms of dairy cows to the transition period","volume":"106","author":"Zhang","year":"2023","journal-title":"J. Dairy Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.3168\/jds.2023-23841","article-title":"Longitudinal characterization of the metabolome of dairy cows transitioning from one lactation to the next: Investigations in blood serum","volume":"107","author":"Ghaffari","year":"2024","journal-title":"J. Dairy Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"9644","DOI":"10.3168\/jds.2023-23359","article-title":"A high-concentrate diet induces colonic inflammation and barrier damage in Hu sheep","volume":"106","author":"Chen","year":"2023","journal-title":"J. Dairy Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"7141","DOI":"10.3168\/jds.2022-21960","article-title":"Invited review: Effect of subacute ruminal acidosis on gut health of dairy cows","volume":"105","author":"Plaizier","year":"2022","journal-title":"J. Dairy Sci."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Artegoitia, V.M., Foote, A.P., Lewis, R.M., and Freetly, H.C. (2017). Rumen fluid metabolomics analysis associated with feed efficiency on crossbred steers. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-02856-0"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1186\/s12967-023-04259-4","article-title":"Sodium butyrate ameliorates diabetic retinopathy in mice via the regulation of gut microbiota and related short-chain fatty acids","volume":"21","author":"Huang","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"118375","DOI":"10.1016\/j.lfs.2020.118375","article-title":"Sodium butyrate promotes milk fat synthesis in bovine mammary epithelial cells via GPR41 and its downstream signalling pathways","volume":"259","author":"Cheng","year":"2020","journal-title":"Life Sci."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Zhao, H., Bai, H., Deng, F., Zhong, R., Liu, L., Chen, L., and Zhang, H. (2022). Chemically protected sodium butyrate improves growth performance and early development and function of small intestine in broilers as one effective substitute for antibiotics. Antibiotics, 11.","DOI":"10.3390\/antibiotics11020132"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.molimm.2022.05.121","article-title":"Nrf2 Activation and NF-Kb & caspase\/bax signaling inhibition by sodium butyrate alleviates LPS-induced cell injury in bovine mammary epithelial cells","volume":"148","author":"Ali","year":"2022","journal-title":"Mol. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"109176","DOI":"10.1016\/j.meatsci.2023.109176","article-title":"Effects of dietary disodium fumarate supplementation on muscle quality, chemical composition, oxidative stress and lipid metabolism of Hu sheep induced by high concentrate diet","volume":"201","author":"Meng","year":"2023","journal-title":"Meat Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.aninu.2023.08.008","article-title":"Dietary supplementation of sodium butyrate enhances lactation performance by promoting nutrient digestion and mammary gland development in dairy cows","volume":"15","author":"Zhang","year":"2023","journal-title":"Anim. Nutr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e13791","DOI":"10.1111\/asj.13791","article-title":"Sodium butyrate administration modulates the ruminal villus height, inflammation-related gene expression, and plasma hormones concentration in dry cows fed a high-fiber diet","volume":"93","author":"Fukumori","year":"2022","journal-title":"Anim. Sci. J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5493","DOI":"10.3168\/jds.2021-21066","article-title":"A high-concentrate diet induces an inflammatory response and oxidative stress and depresses milk fat synthesis in the mammary gland of dairy cows","volume":"105","author":"Ma","year":"2022","journal-title":"J. Dairy Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1146\/annurev.nutr.012809.104648","article-title":"Nutrigenomics, rumen-derived bioactive fatty acids, and the regulation of milk fat synthesis","volume":"31","author":"Bauman","year":"2011","journal-title":"Annu. Rev. Nutr."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Moyes, K.M., S\u00f8rensen, P., and Bionaz, M. (2016). The Impact of Intramammary Escherichia coli Challenge on Liver and Mammary Transcriptome and Cross-Talk in Dairy Cows during Early Lactation Using RNAseq. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0157480"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Kalinowski, C.T., Betancor, M.B., Torrecillas, S., Sprague, M., Larroquet, L., V\u00e9ron, V., Panserat, S., Izquierdo, M.S., Kaushik, S.J., and Fontagn\u00e9-Dicharry, S. (2023). More than an antioxidant: Role of dietary astaxanthin on lipid and glucose metabolism in the liver of rainbow trout (Oncorhynchus mykiss). Antioxidants, 12.","DOI":"10.3390\/antiox12010136"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1530\/JME-20-0324","article-title":"miR-23a\/b-3p promotes hepatic lipid accumulation by regulating Srebp-1c and Fas","volume":"68","author":"Li","year":"2022","journal-title":"J. Mol. Endocrinol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Mun, J., Kim, S., Yoon, H.G., You, Y., Kim, O.K., Choi, K.C., Lee, Y.H., Lee, J., Park, J., and Jun, W. (2019). Water extract of Curcuma longa L. ameliorates non-alcoholic fatty liver disease. Nutrients, 11.","DOI":"10.3390\/nu11102536"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1007\/s11130-022-00996-x","article-title":"Quercetin, Engelitin and Caffeic Acid of Smilax china L. Polyphenols, Stimulate 3T3-L1 Adipocytes to Brown-like Adipocytes via \u03b2 3-AR\/AMPK Signaling Pathway","volume":"77","author":"Kong","year":"2022","journal-title":"Plant Foods Hum. Nutr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"100043","DOI":"10.1016\/j.metop.2020.100043","article-title":"Regulation of hepatic genes related to lipid metabolism and antioxidant enzymes by sodium butyrate supplementation","volume":"7","author":"Honma","year":"2020","journal-title":"Metab. Open"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1016\/j.devcel.2024.01.024","article-title":"SLAM-ITseq identifies that Nrf2 induces liver regeneration through the pentose phosphate pathway","volume":"59","author":"Tan","year":"2024","journal-title":"Dev. Cell."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2173","DOI":"10.1042\/BST20231027","article-title":"The enzymes of the oxidative phase of the pentose phosphate pathway as targets of reactive species: Consequences for NADPH production","volume":"51","author":"Reyes","year":"2023","journal-title":"Biochem. Soc. Trans."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1186\/s12934-020-01398-x","article-title":"The influence of transketolase on lipid biosynthesis in the yeast Yarrowia lipolytica","volume":"19","author":"Dobrowolski","year":"2020","journal-title":"Microb. Cell Fact."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.jgr.2022.04.001","article-title":"Microbiota, co-metabolites, and network pharmacology reveal the alteration of the ginsenoside fraction on inflammatory bowel disease","volume":"47","author":"Wang","year":"2023","journal-title":"J. Ginseng Res."}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/14\/22\/3249\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:31:07Z","timestamp":1760113867000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/14\/22\/3249"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,13]]},"references-count":35,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["ani14223249"],"URL":"https:\/\/doi.org\/10.3390\/ani14223249","relation":{},"ISSN":["2076-2615"],"issn-type":[{"value":"2076-2615","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,13]]}}}