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Metabolites
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Metabolic Research in Dairy Cattle Health
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Metabolic Research in Dairy Cattle Health

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Animal Metabolism".

Deadline for manuscript submissions: 31 December 2026 | Viewed by 2326

Editor

Dr. Wei Yang

E-Mail Website
Guest Editor
College of Animal Science and Technology, Heilongjiang Bayi Agricultural University, Daqing 163319, China
Interests: metabolic diseases of dairy cows; lipid metabolism; biomarkers; signal pathway
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Health and efficient production are fundamental to the dairy farms. However, many mechanisms in aspects of metabolites and metabolism remain unclear, such as the metabolic homeostasis regulation mechanism used during specific production periods; the influence of feed, additives, environmental, and genetic factors on metabolite levels and fluxes; and mechanisms of disease-related metabolic conditions.

This Special Issue presents a collection of original research and review articles that highlight the latest discoveries and advances in the field of metabolics in dairy science, focused on the regulation mechanism of metabolic homeostasis in dairy cattle; the metabolic fate of feed ingredients and additives; the metabolic regulatory influence of feed, additives, environmental, and genetic factors on microbes and health in dairy cows; the mechanisms of disease-related metabolic conditions; the measurement, analysis, and/or biological roles of metabolite biomarkers; and other metabolic aspects of dairy cattle health. The selected articles will strengthen our understanding of metabolic processes related to improving both health and efficient production for dairy cows.

This Special Issue of Metabolites, titled “Metabolic Research in Dairy Cattle Health”, will be dedicated to dealing with the role of metabolites concerned with homeostasis of dairy cattle. This Special Issue will publish results focused on the diagnosis or regulatory roles of various metabolites in ruminant health and sustainable production, with different biological tools and novel analysis concepts.

Dr. Wei Yang
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • dairy cow
  • nutrient metabolism
  • feed ingredients
  • additives
  • disease
  • microbes
  • metabolite biomarkers

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Published Papers (3 papers)

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Research

26 pages, 7002 KB  
Article
Proteomics and Metabolomics Reveal Novel Impacts of Choline Supply on Calf Hepatocytes Experiencing Accumulation During a Fatty Acid Challenge
by Yaqi Chang, Bin Jia, Yaran Si, Zexin Zhang, Jiachen Liu, Yue Gao, Junhao Wang, Yanhui Wang, Juan J. Loor, Bingbing Zhang and Wei Yang
Metabolites 2026, 16(7), 451; https://doi.org/10.3390/metabo16070451 - 26 Jun 2026
Viewed by 604
Abstract
Background/Objectives: Exposure to high and sustained levels of non-esterified fatty acids (NEFA) in the peripartal period is the main cause of fatty liver disease in dairy cows. Rumen-protected choline is often fed as part of the nutritional management of peripartal cows, with in [...] Read more.
Background/Objectives: Exposure to high and sustained levels of non-esterified fatty acids (NEFA) in the peripartal period is the main cause of fatty liver disease in dairy cows. Rumen-protected choline is often fed as part of the nutritional management of peripartal cows, with in vivo and in vitro data indicating positive effects of this nutrient on alleviating liver lipid accumulation. Although hepatic molecular mechanisms associated with choline supply have been studied using a target gene, protein, or metabolite approach, application of high-throughput technologies could vastly enhance fundamental knowledge on the functional role of choline. The main objective was to challenge isolated hepatocytes with a mixture of NEFA and determine proteome- and metabolome-wide effects in response to choline supply. Methods: Three healthy female calves (1 d old, 30–45 kg) were sacrificed to harvest hepatocytes. During a 12 h incubation, isolated hepatocytes were challenged without NEFA (control), 1.2 mM NEFA (c9-18:1, 18:2, 16:0, 18:0, and c9-16:1 at 43.5%, 4.9%, 31.9%, 14.4%, and 5.3% of total NEFA, respectively), or NEFA for 6 h followed by 10 μM choline chloride for another 6 h (NEFA + Chol). iTRAQ labeling-based protein profiling and GC/MS-based metabolomics profiling were used to determine changes in proteins and metabolites. Differentially abundant proteins for each group comparison were determined at a threshold of 1.4-fold change. Differences in metabolite profiles were assessed via pairwise comparisons. A subset of differentially abundant proteins was validated via qRT-PCR and Western blotting. Results: Compared with the control, there were 90 proteins and 22 metabolites in the NEFA group, and 83 proteins and 29 metabolites in the NEFA + Chol. Compared with NEFA, there were 49 proteins and 17 metabolites in the NEFA + Chol group. Greater abundance of hexokinase-1 (HK1), fructose-bisphosphate aldolase (ALDOA), mitochondrial pyruvate carrier 1 (MPC1), and increased concentrations of lactate with high NEFA treatment alone suggested greater glycolytic and TCA cycle activity. Accumulation of triacylglycerol in the NEFA group was associated with lipotoxicity and markers of inflammation, such as greater abundance of prostaglandin reductase 1 (PTGR1), serious cell autophagy processes, such as greater abundance of cell division cycle 42 (CDC42), and NFκB-related proteins. Choline supplementation reduced TAG partly due to greater VLDL secretion driven by greater abundance of diacylglycerol acyltransferase (DGAT1), perilipin 3 (PLIN3), and apolipoprotein C-III (APOC3). In addition, a greater abundance of carnitine O-palmitoyltransferase 1b (CPT1B) with choline suggested enhanced mitochondrial β-oxidation. Activation of the CDC42/JNK pathway and ROS/NFκB axis-related proteins, along with depressed PI3K/AKT/RAC-related proteins, indicated enhanced mitochondrial autophagy in response to NEFA. Conclusions: Overall, data confirmed published effects of choline on TAG accumulation, VLDL secretion, and fatty acid oxidation, while highlighting negative effects of NEFA on the respiratory electron transport chain, autophagy, and inflammatory processes. Full article
(This article belongs to the Special Issue Metabolic Research in Dairy Cattle Health)
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23 pages, 8418 KB  
Article
Untargeted LC–MS Plasma Metabolomics Reveals Altered Amino Acid and Carbohydrate Metabolism in Dairy Calves Supplemented with Direct-Fed Microbials
by Oludotun O. Adelusi, David P. Casper, John O. Adebayo, Ahmed E. Kholif, Ibukun M. Ogunade and Uchenna Y. Anele
Metabolites 2026, 16(7), 441; https://doi.org/10.3390/metabo16070441 - 25 Jun 2026
Viewed by 545
Abstract
Background/Objectives: Direct-fed microbials (DFMs) are widely used in dairy calves to improve gut health and mitigate neonatal disorders, yet their systemic metabolic effects remain poorly defined. This study evaluated the impact of DFM supplementation on the plasma metabolome of pre-weaned dairy calves [...] Read more.
Background/Objectives: Direct-fed microbials (DFMs) are widely used in dairy calves to improve gut health and mitigate neonatal disorders, yet their systemic metabolic effects remain poorly defined. This study evaluated the impact of DFM supplementation on the plasma metabolome of pre-weaned dairy calves using untargeted liquid chromatography–mass spectrometry (LC–MS). Methods: Eighty-six Holstein bull calves (2 to 5 days old) were assigned to one of four treatments in a 2 × 2 factorial randomized complete block design: Lactobacillus plantarum in starter (CLP), a culture mix of Bifidobacterium animalis and Lactobacillus animalis in milk replacer (BBCM), and a combination of both (CMLP), or no supplementation (CON). Blood samples collected on days 0 and 56 were subjected to metabolomic profiling, and metabolites were annotated using Human Metabolome Database and Kyoto Encyclopedia of Genes and Genomes databases. Results: A total of 231 plasma metabolites were detected. Compared with CON, 24 metabolites were differentially abundant in DFM-treated calves (fold change ≥ 1.2 or ≤ 0.83; p ≤ 0.05). Supplemented calves exhibited increased abundances of ketone functional groups, aldehydes and amino acid-related metabolites. Metabolite set enrichment analysis identified 11 significantly enriched pathways. Branched-chain amino acid degradation pathways (valine, leucine, and isoleucine) were enriched in CLP and CMLP calves, whereas carbohydrate metabolism pathways, including pentose and glucuronate interconversions, were enriched in the CLP and BBCM groups. Conclusions: These findings demonstrate that DFM supplementation modulates systemic metabolism in dairy calves, particularly pathways involved in amino acid and carbohydrate utilization, suggesting enhanced metabolic efficiency during early life. Full article
(This article belongs to the Special Issue Metabolic Research in Dairy Cattle Health)
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18 pages, 3656 KB  
Article
Free Fatty Acids and Endotoxins Synergically Induce Pyroptosis in Bovine Hepatocytes
by Dan Li, Yuan Tian, Lei Tian, Hang Yu, Le Zhang, Song Wang, Changsheng Lei, Pin Long, Tao Peng, Lei Liu and Yingfang Zhou
Metabolites 2026, 16(1), 53; https://doi.org/10.3390/metabo16010053 - 8 Jan 2026
Cited by 1 | Viewed by 729
Abstract
Background/Objectives: Elevated circulating non-esterified fatty acids (NEFAs) are closely associated with hepatic inflammatory injury in dairy cattle, simultaneously with the entry of lipopolysaccharide (LPS) into the liver. This study aimed to investigate the synergistic effects of NEFAs and LPS on pyroptosis in [...] Read more.
Background/Objectives: Elevated circulating non-esterified fatty acids (NEFAs) are closely associated with hepatic inflammatory injury in dairy cattle, simultaneously with the entry of lipopolysaccharide (LPS) into the liver. This study aimed to investigate the synergistic effects of NEFAs and LPS on pyroptosis in bovine hepatocytes. Methods: Primary bovine hepatocytes were allocated into control, NEFA, NEFA + LPS, NEFA + LPS + Caspase-1 inhibitor, and NEFA + LPS + NLRP3 inhibitor groups. Levels and activation of pyroptosis-related markers (NLRP3, ASC, Caspase-1, GSDMD, IL-18 and IL-1β) were measured. Results: NEFAs alone upregulated these markers in a dose-dependent manner. Compared to NEFAs alone, NEFA + LPS co-treatment significantly enhanced levels of the markers, increased IL-1β secretion, and promoted NLRP3/Caspase-1 co-localization and Caspase-1activity. Notably, these effects of NEFA + LPS were attenuated by the NLRP3 or Caspase-1 inhibitors. Similar results were obtained when repeating the experiments in carcinoma HepG2 cells. Also, a random liver section from the subclinical ketotic cows displayed a higher fluorescence intensity of NLRP3 and Caspase-1 and stronger co-localization than that from a healthy cow. Conclusions: NEFAs and LPS synergistically contribute to pyroptosis in bovine hepatocytes by enhancing NLRP3 inflammasome assembly and subsequent Caspase-1 activation, providing a potential target for mitigating hepatic injury. Full article
(This article belongs to the Special Issue Metabolic Research in Dairy Cattle Health)
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