{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:14:59Z","timestamp":1792685699022,"version":"4.5.0"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T00:00:00Z","timestamp":1764720000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:p>\n                    The periparturient period creates an intense energy demand due to the onset of lactation, which requires substantial glucose for milk synthesis, particularly in high producing cows, contributing to a high incidence of postpartum metabolic disease. We explored the transcriptomic adaptation of subcutaneous adipose tissue (AT), with a specific focus on metabolic gene networks and the mitochondrial component. Mitochondria coordinate cellular energy dynamics by linking the oxidation of nutrients to ATP synthesis via oxidative phosphorylation (OXPHOS). However, their role in postpartum metabolic disease is not clear. We therefore re-analysed a longitudinal RNA-seq dataset of subcutaneous AT from 12 healthy multiparous Holstein cows, sampled pre-calving and at two early-lactation time-points, to explore mitochondrial pathways. This analysis revealed downregulation of differentially expressed genes (DEGs), encoding components of the electron transport system and OXPHOS, in the postpartum phase, concurrent with a shift to DEGs associated with glycolysis. Given the observed glycolytic shift, an analysis of plasma lactate during the periparturient period was undertaken, to explore how this glycolysis-derived substrate fluctuates in this altered metabolic state. A postpartum decline in plasma lactate, alongside rising\n                    <jats:italic>\u03b2<\/jats:italic>\n                    -hydroxybutyrate, was further demonstrated in clinical ketotic cows, revealing a potential metabolic toggle between lactate and ketones; aligning with the concept that fuel sources will alter depending on redox and metabolic conditions. This supports the emerging view that ketones are not merely pathological markers but may serve as adaptive metabolic signals, warranting further investigation into their role in dairy cow metabolism. Further understanding of how mitochondria function during this energy-intensive postpartum phase of the dairy cow, may help elucidate how adipose tissue contributes to metabolic resilience or perturbation during early lactation.\n                  <\/jats:p>","DOI":"10.3389\/fvets.2025.1676955","type":"journal-article","created":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T14:25:11Z","timestamp":1764771911000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Bovine adipose mitochondrial adaptation and a potential lactate\u2013ketone toggle in early lactation"],"prefix":"10.3389","volume":"12","author":[{"given":"Nial J.","family":"O\u2019Boyle","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Chirivi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ursula","family":"Abou-Rjeileh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Salcedo-Tacuma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 M.","family":"dos Santos Neto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Crystal","family":"Prom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jair","family":"Parales-Gir\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam L.","family":"Lock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhard","family":"St\u00f6ger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Chakrabarti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. Andres","family":"Contreras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,3]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.3389\/fvets.2025.1470391","article-title":"Animal health and nutrition: metabolic disorders in cattle and improvement strategies","volume":"12","author":"Kang","year":"2025","journal-title":"Front Vet Sci"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"100298","DOI":"10.1016\/j.animal.2021.100298","article-title":"Review: perspective on high-performing dairy cows and herds","volume":"15","author":"Britt","year":"2021","journal-title":"Animal"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1093\/af\/vfac059","article-title":"Feeding dairy cows for improved metabolism and health","volume":"12","author":"Martins","year":"2022","journal-title":"Anim Front"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/s40104-017-0174-4","article-title":"Adipose tissue lipolysis and remodeling during the transition period of dairy cows","volume":"8","author":"Contreras","year":"2017","journal-title":"J Anim Sci Biotechnol"},{"key":"ref5","volume-title":"Navigating metabolism","author":"Chandel","year":"2015"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"3670","DOI":"10.3168\/jds.2021-21225","article-title":"Symposium review: mechanistic insights into adipose tissue inflammation and oxidative stress in periparturient dairy cows*","volume":"105","author":"Zachut","year":"2022","journal-title":"J Dairy Sci"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"832","DOI":"10.3390\/ani14060832","article-title":"The complex interplay of insulin resistance and metabolic inflammation in transition dairy cows","volume":"14","author":"Qiao","year":"2024","journal-title":"Animals"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"7608","DOI":"10.3168\/jds.2017-14318","article-title":"Short communication: effects of body fat mobilization on macrophage infiltration in adipose tissue of early lactation dairy cows","volume":"101","author":"De Koster","year":"2018","journal-title":"J Dairy Sci"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1016\/j.cmet.2018.03.008","article-title":"The science and translation of lactate shuttle theory","volume":"27","author":"Brooks","year":"2018","journal-title":"Cell Metab"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1016\/j.cmet.2016.12.022","article-title":"Multi-dimensional roles of ketone bodies in fuel metabolism, signaling, and therapeutics","volume":"25","author":"Puchalska","year":"2017","journal-title":"Cell Metab"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1186\/s12864-020-07235-0","article-title":"Transcriptomic profiling of adipose tissue inflammation, remodeling, and lipid metabolism in periparturient dairy cows (Bos taurus)","volume":"21","author":"Salcedo-Tacuma","year":"2020","journal-title":"BMC Genomics"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1080\/01652176.2017.1354561","article-title":"Disturbed bovine mitochondrial lipid metabolism: a review","volume":"37","author":"JH","year":"2017","journal-title":"Vet Q"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"842","DOI":"10.3168\/jds.2021-20855","article-title":"Lipopolysaccharide induces lipolysis and insulin resistance in adipose tissue from dairy cows","volume":"105","author":"Chirivi","year":"2022","journal-title":"J Dairy Sci"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"4306","DOI":"10.3168\/jds.2022-22402","article-title":"Oleic acid abomasal infusion limits lipolysis and improves insulin sensitivity in adipose tissue from periparturient dairy cows","volume":"106","author":"Abou-Rjeileh","year":"2023","journal-title":"J Dairy Sci"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"W234","DOI":"10.1093\/nar\/gkz240","article-title":"NetworkAnalyst 3.0: a visual analytics platform for comprehensive gene expression profiling and meta-analysis","volume":"47","author":"Zhou","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: a bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"D1541","DOI":"10.1093\/nar\/gkaa1011","article-title":"MitoCarta3.0: an updated mitochondrial proteome now with sub-organelle localization and pathway annotations","volume":"49","author":"Rath","year":"2020","journal-title":"Nucleic Acids Res"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"D605","DOI":"10.1093\/nar\/gkaa1074","article-title":"The STRING database in 2021: customizable protein-protein networks, and functional characterization of user-uploaded gene\/measurement sets","volume":"49","author":"Szklarczyk","year":"2021","journal-title":"Nucleic Acids Res"},{"key":"ref19","volume-title":"Practical guide to cluster analysis in R: Unsupervised machine learning \/","author":"Kassambara","year":"2017"},{"key":"ref20","year":"2023"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1109\/MCSE.2007.55","article-title":"Matplotlib: a 2D graphics environment","volume":"9","author":"Hunter","year":"2007","journal-title":"Comput Sci Eng"},{"key":"ref22","year":""},{"key":"ref23","year":""},{"key":"ref24","year":""},{"key":"ref25","doi-asserted-by":"publisher","first-page":"9514","DOI":"10.3168\/jds.2023-23409","article-title":"Lipolysis inhibition as a treatment of clinical ketosis in dairy cows: a randomized clinical trial","volume":"106","author":"Chirivi","year":"2023","journal-title":"J Dairy Sci"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1007\/s11010-014-2236-7","article-title":"Enhanced ROS production and oxidative damage in subcutaneous white adipose tissue mitochondria in obese and type 2 diabetes subjects","volume":"399","author":"Chattopadhyay","year":"2015","journal-title":"Mol Cell Biochem"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"236","DOI":"10.3389\/fimmu.2020.00236","article-title":"Editorial: role of ribonucleases in immune response regulation during infection and Cancer","volume":"11","author":"Boix","year":"2020","journal-title":"Front Immunol"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1210\/rp.57.1.435","article-title":"Prolactin modulation of immune and inflammatory responses","volume":"57","author":"Yu-Lee","year":"2002","journal-title":"Recent Prog Horm Res"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"7272","DOI":"10.3390\/ijms21197272","article-title":"CaMKII\u03b2 in neuronal development and plasticity: an emerging candidate in brain diseases","volume":"21","author":"Nicole","year":"2020","journal-title":"Int J Mol Sci"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1016\/j.ghir.2014.04.007","article-title":"IGFBP-3: a cell fate pivot in cancer and disease","volume":"24","author":"Johnson","year":"2014","journal-title":"Growth Hormon IGF Res"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"1449","DOI":"10.1152\/physrev.00003.2016","article-title":"Heme Oxygenases in cardiovascular health and disease","volume":"96","author":"Ayer","year":"2016","journal-title":"Physiol Rev"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"945","DOI":"10.7754\/Clin.Lab.2012.121115","article-title":"Human serum albumin and its relation with oxidative stress","volume":"59","author":"Sitar","year":"2013","journal-title":"Clin Lab"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"3128","DOI":"10.3168\/jds.S0022-0302(03)73914-9","article-title":"Increased levels of LPS-binding protein in bovine blood and Milk following bacterial lipopolysaccharide challenge","volume":"86","author":"Bannerman","year":"2003","journal-title":"J Dairy Sci"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1016\/S1471-4906(02)02233-0","article-title":"Lipopolysaccharide recognition: CD14, TLRs and the LPS-activation cluster","volume":"23","author":"Triantafilou","year":"2002","journal-title":"Trends Immunol"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"6611","DOI":"10.1093\/nar\/gkaa393","article-title":"DNA damage invokes mitophagy through a pathway involving Spata18","volume":"48","author":"Dan","year":"2020","journal-title":"Nucleic Acids Res"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/J.NEURON.2014.12.007","article-title":"The roles of PINK1, Parkin, and mitochondrial Fidelity in Parkinson\u2019s disease","volume":"85","author":"Pickrell","year":"2015","journal-title":"Neuron"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1152\/physrev.00041.2020","article-title":"Mitochondrial calcium exchange in physiology and disease","volume":"102","author":"Garbincius","year":"2022","journal-title":"Physiol Rev"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1038\/s41580-019-0173-8","article-title":"Mitochondria as multifaceted regulators of cell death","volume":"21","author":"Bock","year":"2020","journal-title":"Nat Rev Mol Cell Biol"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"7023","DOI":"10.1113\/JP273839","article-title":"Oxidative phosphorylation: regulation and role in cellular and tissue metabolism","volume":"595","author":"Wilson","year":"2017","journal-title":"J Physiol"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"1307","DOI":"10.3390\/biomedicines12061307","article-title":"UCP2, a member of the mitochondrial uncoupling proteins: an overview from physiological to pathological roles","volume":"12","author":"Nesci","year":"2024","journal-title":"Biomedicine"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1126\/science.1160809","article-title":"Understanding the Warburg effect: the metabolic requirements of cell proliferation","volume":"324","author":"Vander Heiden","year":"2009","journal-title":"Science"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"848394","DOI":"10.3389\/fonc.2022.848394","article-title":"Metabolic reprogramming in adipose tissue during Cancer Cachexia","volume":"12","author":"Weber","year":"2022","journal-title":"Front Oncol"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1038\/s41392-021-00659-4","article-title":"The molecular biology of pancreatic adenocarcinoma: translational challenges and clinical perspectives","volume":"6","author":"Wang","year":"2021","journal-title":"Signal Transduct Target Ther"},{"key":"ref44","doi-asserted-by":"publisher","DOI":"10.21037\/tbcr-20-53","article-title":"Reprogramming of fatty acid metabolism in breast cancer: a narrative review","volume":"2","author":"Zhao","year":"2021","journal-title":"Transl Breast Cancer Res"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"4252","DOI":"10.1021\/pr200425h","article-title":"Involvement of skeletal muscle protein, glycogen, and fat metabolism in the adaptation on early lactation of dairy cows","volume":"10","author":"Kuhla","year":"2011","journal-title":"J Proteome Res"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1186\/s13046-024-02994-0","article-title":"A glutamine tug-of-war between cancer and immune cells: recent advances in unraveling the ongoing battle","volume":"43","author":"Wang","year":"2024","journal-title":"J Exp Clin Cancer Res"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1152\/physrev.00017.2012","article-title":"Hypoxia and adipose tissue function and dysfunction in obesity","volume":"93","author":"Trayhurn","year":"2013","journal-title":"Physiol Rev"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"1803","DOI":"10.3168\/jds.s0022-0302(88)79749-0","article-title":"Net portal-drained visceral and hepatic metabolism of glucose, L-lactate, and nitrogenous compounds in lactating Holstein cows","volume":"71","author":"Reynolds","year":"1988","journal-title":"J Dairy Sci"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1038\/s42255-018-0021-8","article-title":"Metabolic adaptation and maladaptation in adipose tissue","volume":"1","author":"Chouchani","year":"2019","journal-title":"Nat Metab"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1038\/nature13490","article-title":"Functional polarization of tumour-associated macrophages by tumour-derived lactic acid","volume":"513","author":"Colegio","year":"2014","journal-title":"Nature"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.ymben.2023.02.002","article-title":"13C-metabolic flux analysis of 3T3-L1 adipocytes illuminates its core metabolism under hypoxia","volume":"76","author":"Oates","year":"2023","journal-title":"Metab Eng"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"637","DOI":"10.2337\/db21-0535","article-title":"Lactate is a key mediator that links obesity to insulin resistance via modulating cytokine production from adipose tissue","volume":"71","author":"Lin","year":"2022","journal-title":"Diabetes"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1042\/bj1860047","article-title":"Net hepatic and splanchnic metabolism of lactate, pyruvate and propionate in dairy cows in vivo in relation to lactation and nutrient supply","volume":"186","author":"Baird","year":"1980","journal-title":"Biochem J"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/j.cmet.2010.02.012","article-title":"An autocrine lactate loop mediates insulin-dependent inhibition of lipolysis through GPR81","volume":"11","author":"Ahmed","year":"2010","journal-title":"Cell Metab"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1016\/j.rvsc.2016.06.012","article-title":"Dairy cows affected by ketosis show alterations in innate immunity and lipid and carbohydrate metabolism during the dry off period and postpartum","volume":"107","author":"Zhang","year":"2016","journal-title":"Res Vet Sci"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"8380","DOI":"10.3168\/jds.2021-20330","article-title":"Invited review: the influence of immune activation on transition cow health and performance-a critical evaluation of traditional dogmas","volume":"104","author":"Horst","year":"2021","journal-title":"J Dairy Sci"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"3367","DOI":"10.3168\/jds.2023-23904","article-title":"Invited review: ketone biology\u2014the shifting paradigm of ketones and ketosis in the dairy cow","volume":"107","author":"Rico","year":"2024","journal-title":"J Dairy Sci"}],"container-title":["Frontiers in Veterinary Science"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2025.1676955\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T14:25:14Z","timestamp":1764771914000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2025.1676955\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,3]]},"references-count":57,"alternative-id":["10.3389\/fvets.2025.1676955"],"URL":"https:\/\/doi.org\/10.3389\/fvets.2025.1676955","relation":{},"ISSN":["2297-1769"],"issn-type":[{"value":"2297-1769","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,3]]},"article-number":"1676955"}}