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Beijing Municipal Education Commission","award":["KM202010020010"],"award-info":[{"award-number":["KM202010020010"]}]},{"name":"Science and Technology General Project of Beijing Municipal Education Commission","award":["KM202010020010"],"award-info":[{"award-number":["KM202010020010"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Ketosis, especially its subclinical form, is frequently observed in high-yielding dairy cows and is linked to various diseases during the transition period. Although adipose tissue plays a significant role in the development of metabolic disorders, its exact impact on the emergence of subclinical ketosis (SCK) is still poorly understood. The objectives of this study were to characterize and compare the profiling of transcriptome and lipidome of blood and adipose tissue between SCK and healthy cows and investigate the potential correlation between metabolic disorders and lipid metabolism. We obtained blood and adipose tissue samples from healthy cows (CON, n = 8, \u03b2-hydroxybutyric acid concentration &lt; 1.2 mmol\/L) and subclinical ketotic cows (SCK, n = 8, \u03b2-hydroxybutyric acid concentration = 1.2\u20133.0 mmol\/L) for analyzing biochemical parameters, transcriptome, and lipidome. We found that serum levels of nonesterified fatty acids, malonaldehyde, serum amyloid A protein, IL-1\u03b2, and IL-6 were higher in SCK cows than in CON cows. Levels of adiponectin and total antioxidant capacity were higher in serum and adipose tissue from SCK cows than in CON cows. The top enriched pathways in whole blood and adipose tissue were associated with immune and inflammatory responses and sphingolipid metabolism, respectively. The accumulation of ceramide and sphingomyelin in adipose tissue was paralleled by an increase in genes related to ceramide biosynthesis, lipolysis, and inflammation and a decrease in genes related to ceramide catabolism, lipogenesis, adiponectin production, and antioxidant enzyme systems. Increased ceramide concentrations in blood and adipose tissue correlated with reduced insulin sensitivity. The current results indicate that the lipid profile of blood and adipose tissue is altered with SCK and that certain ceramide species correlate with metabolic health. Our research suggests that disruptions in ceramide metabolism could be crucial in the progression of SCK, exacerbating conditions such as insulin resistance, increased lipolysis, inflammation, and oxidative stress, providing a potential biomarker of SCK and a novel target for nutritional manipulation and pharmacological therapy.<\/jats:p>","DOI":"10.3390\/antiox13050614","type":"journal-article","created":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T12:02:23Z","timestamp":1715947343000},"page":"614","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Multi-Omics Reveals Disrupted Immunometabolic Homeostasis and Oxidative Stress in Adipose Tissue of Dairy Cows with Subclinical Ketosis: A Sphingolipid-Centric Perspective"],"prefix":"10.3390","volume":"13","author":[{"given":"Huiying","family":"Zhao","sequence":"first","affiliation":[{"name":"Beijing Key Laboratory of Dairy Cow Nutrition, College of Animal Science and Technology, Beijing University of Agriculture, Beijing 102206, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liuxue","family":"Li","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Dairy Cow Nutrition, College of Animal Science and Technology, Beijing University of Agriculture, Beijing 102206, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Tan","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Dairy Cow Nutrition, College of Animal Science and Technology, Beijing University of Agriculture, Beijing 102206, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Dairy Cow Nutrition, College of Animal Science and Technology, Beijing University of Agriculture, Beijing 102206, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Dairy Cow Nutrition, College of Animal Science and Technology, Beijing University of Agriculture, Beijing 102206, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchao","family":"Zhao","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Dairy Cow Nutrition, College of Animal Science and Technology, Beijing University of Agriculture, Beijing 102206, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9076-5749","authenticated-orcid":false,"given":"Linshu","family":"Jiang","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Dairy Cow Nutrition, College of Animal Science and Technology, Beijing University of Agriculture, Beijing 102206, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.cvfa.2004.06.013","article-title":"Dry matter intake and energy balance in the transition period","volume":"20","author":"Grummer","year":"2004","journal-title":"Vet. Clin. N. Am. Food Anim. Pract."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2259","DOI":"10.3168\/jds.S0022-0302(99)75474-3","article-title":"Biology of dairy cows during the transition period: The final frontier?","volume":"82","author":"Drackley","year":"1999","journal-title":"J. Dairy. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/S0749-0720(15)30102-X","article-title":"Ruminant adaptation to negative energy balance\u2014Influences on the etiology of ketosis and fatty liver","volume":"16","author":"Herdt","year":"2000","journal-title":"Vet. Clin. N. Am. Food Anim. Pract."},{"key":"ref_4","first-page":"S1","article-title":"Interaction between metabolic challenges and productivity in high yielding dairy cows","volume":"63","author":"Opsomer","year":"2015","journal-title":"Jpn. J. Vet. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/S0749-0720(15)31046-X","article-title":"Subclinical Ketosis in Dairy Cows","volume":"4","author":"Andersson","year":"1988","journal-title":"Vet. Clin. N. Am. Food Anim. Pract."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.anireprosci.2013.11.007","article-title":"Interactions between negative energy balance, metabolic diseases, uterine health and immune response in transition dairy cows","volume":"144","author":"Esposito","year":"2014","journal-title":"Anim. Reprod. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Zhang, H., Wu, L., Xu, C., Xia, C., Sun, L., and Shu, S. (2013). Plasma metabolomic profiling of dairy cows affected with ketosis using gas chromatography\/mass spectrometry. BMC Vet. Res., 9.","DOI":"10.1186\/1746-6148-9-186"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1080\/01652176.2014.962116","article-title":"Plasma metabolic profiling of dairy cows affected with clinical ketosis using LC\/MS technology","volume":"34","author":"Li","year":"2014","journal-title":"Vet. Quart."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Shahzad, K., Lopreiato, V., Liang, Y., Trevisi, E., Osorio, J.S., Xu, C., and Loor, J.J. (2019). Hepatic metabolomics and transcriptomics to study susceptibility to ketosis in response to prepartal nutritional management. J. Anim. Sci. Biotechnol., 10.","DOI":"10.1186\/s40104-019-0404-z"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"136813","DOI":"10.1016\/j.foodchem.2023.136813","article-title":"Multi-omics analysis reveals that the metabolite profile of raw milk is associated with dairy cows\u2019 health status","volume":"428","author":"Zhao","year":"2023","journal-title":"Food Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2548","DOI":"10.1210\/jc.2004-0395","article-title":"Adipose tissue as an endocrine organ","volume":"89","author":"Kershaw","year":"2004","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.2460\/ajvr.2004.65.1319","article-title":"Insulin resistance and abomasal motility disorders in cows detected by use of abomasoduodenal electromyography after surgical correction of left displaced abomasum","volume":"65","author":"Pravettoni","year":"2004","journal-title":"Am. J. Vet. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.cvfa.2013.04.002","article-title":"Insulin resistance in dairy cows","volume":"29","author":"Opsomer","year":"2013","journal-title":"Vet. Clin. N. Am. Food Anim. Pract."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3108","DOI":"10.3168\/jds.2012-6097","article-title":"Regulation of bovine adipose tissue metabolism during lactation. 7. Metabolism and gene expression as a function of genetic merit and dietary energy intake","volume":"96","author":"Rocco","year":"2013","journal-title":"J. Dairy. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Mellouk, N., Rame, C., Naquin, D., Jaszczyszyn, Y., Touz\u00e9, J.L., Briant, E., Guillaume, D., Ntallaris, T., Humblot, P., and Dupont, J. (2019). Impact of the severity of negative energy balance on gene expression in the subcutaneous adipose tissue of periparturient primiparous Holstein dairy cows: Identification of potential novel metabolic signals for the reproductive system. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0222954"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2837","DOI":"10.1093\/jas\/skz132","article-title":"Adipose tissue proteomic analysis in ketotic or healthy Holstein cows in early lactation","volume":"97","author":"Xu","year":"2019","journal-title":"J. Anim. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5018","DOI":"10.3168\/jds.2022-22941","article-title":"Gene co-expression network and differential expression analyses of subcutaneous white adipose tissue reveal novel insights into the pathological mechanisms underlying ketosis in dairy cows","volume":"106","author":"Ning","year":"2023","journal-title":"J. Dairy. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2817","DOI":"10.1111\/febs.12202","article-title":"On the future of mass-spectrometry-based lipidomics","volume":"280","year":"2013","journal-title":"FEBS J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.rvsc.2016.10.001","article-title":"Altered plasma lipidome profile of dairy cows with fatty liver disease","volume":"110","author":"Gerspach","year":"2017","journal-title":"Res. Vet. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"289","DOI":"10.2144\/btn-2020-0088","article-title":"A clinically validated human capillary blood transcriptome test for global systems biology studies","volume":"69","author":"Toma","year":"2020","journal-title":"BioTechniques"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Chaussabel, D., Pascual, V., and Banchereau, J. (2010). Assessing the human immune system through blood transcriptomics. BMC Biol., 8.","DOI":"10.1186\/1741-7007-8-84"},{"key":"ref_22","unstructured":"NRC (2001). Nutrient Requirements of Dairy Cattle."},{"key":"ref_23","unstructured":"Association of Official Analytical Chemists (AOAC) (2012). Official Methods of Analysis, Association of Official Analytical Chemists."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3583","DOI":"10.3168\/jds.S0022-0302(91)78551-2","article-title":"Methods for dietary fiber, neutral detergent fiber, and nonstarch polysaccharides in relation to animal nutrition","volume":"74","author":"Robertson","year":"1991","journal-title":"J. Dairy. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/1751-0147-49-29","article-title":"A model to estimate insulin sensitivity in dairy cows","volume":"49","author":"Holtenius","year":"2007","journal-title":"Acta Vet. Scand."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2334","DOI":"10.3168\/jds.2016-11790","article-title":"Far-off and close-up dry matter intake modulate indicators of immunometabolic adaptations to lactation in subcutaneous adipose tissue of pasture-based transition dairy cows","volume":"100","author":"Farina","year":"2017","journal-title":"J. Dairy. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"758","DOI":"10.3168\/jds.2015-10046","article-title":"Body condition score and plane of nutrition prepartum affect adipose tissue transcriptome regulators of metabolism and inflammation in grazing dairy cows during the transition period","volume":"99","author":"Kanwal","year":"2016","journal-title":"J. Dairy. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6439","DOI":"10.3168\/jds.2019-17813","article-title":"Body condition alters glutathione and nuclear factor erythroid 2-like 2 (NFE2L2)- related antioxidant network abundance in subcutaneous adipose tissue of periparturient Holstein cows","volume":"103","author":"Liang","year":"2020","journal-title":"J. Dairy. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1097\/MPG.0000000000002875","article-title":"Lipidomics in nonalcoholic fatty liver disease: Exploring serum lipids as biomarkers for pediatric nonalcoholic fatty liver disease","volume":"71","author":"Draijer","year":"2020","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Chaves-Filho, A.B., Peixoto, A.S., Castro, \u00c3., Oliveira, T.E., Perandini, L.A., Moreira, R.J., Silva, R.P., Silva, B.P., Moretti, E.H., and Steiner, A.A. (2023). Futile cycle of \u03b2-oxidation and de novo lipogenesis are associated with essential fatty acids depletion in lipoatrophy. Biochim. Biophys. Acta Mol. Cell Biol. Lipids, 1868.","DOI":"10.1016\/j.bbalip.2022.159264"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"9151","DOI":"10.3168\/jds.2018-15879","article-title":"Association of dry matter intake and energy balance prepartum and postpartum with health disorders postpartum: Part II. Ketosis and clinical mastitis","volume":"102","author":"Risco","year":"2019","journal-title":"J. Dairy. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Kehrli, J.M., Neil, J., Burvenich, C., Goff, J., Lippolis, J., Reinhardt, T., and Nonnecke, B. (2006). Energy and Protein Effects on the Immune System, Wageningen Academic Publishers.","DOI":"10.3920\/9789086865666_018"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"5915","DOI":"10.1074\/jbc.M807852200","article-title":"Bacterial endotoxin stimulates adipose lipolysis via Toll-like receptor 4 and extracellular signal-regulated kinase pathway","volume":"284","author":"Zu","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.tem.2014.03.002","article-title":"Lipolysis in lipid turnover, cancer cachexia, and obesity-induced insulin resistance","volume":"25","author":"Arner","year":"2014","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Chirivi, M., Cortes, D., Rendon, C.J., and Contreras, G.A. (2024). Lipolysis inhibition as a treatment of clinical ketosis in dairy cows: Effects on adipose tissue metabolic and immune responses. J. Dairy. Sci., in press.","DOI":"10.3168\/jds.2023-23998"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2735","DOI":"10.3168\/jds.2006-759","article-title":"Induction of hyperlipidemia by intravenous infusion of tallow emulsion causes insulin resistance in holstein cows","volume":"90","author":"Pires","year":"2007","journal-title":"J. Dairy. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/s41392-022-01073-0","article-title":"Trends in insulin resistance: Insights into mechanisms and therapeutic strategy","volume":"7","author":"Li","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"skab221","DOI":"10.1093\/jas\/skab221","article-title":"Effects of serine palmitoyltransferase inhibition by myriocin in ad libitum-fed and nutrient-restricted ewes","volume":"99","author":"Davis","year":"2021","journal-title":"J. Anim. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/nrm.2017.107","article-title":"Sphingolipids and their metabolism in physiology and disease","volume":"19","author":"Hannun","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"40198","DOI":"10.1074\/jbc.C112.404012","article-title":"Mammalian ORMDL proteins mediate the feedback response in ceramide biosynthesis","volume":"287","author":"Siow","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/nrm2329","article-title":"Principles of bioactive lipid signalling: Lessons from sphingolipids","volume":"9","author":"Hannun","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"7757","DOI":"10.3168\/jds.2015-9519","article-title":"Plasma ceramides are elevated in overweight Holstein dairy cows experiencing greater lipolysis and insulin resistance during the transition from late pregnancy to early lactation","volume":"98","author":"Rico","year":"2015","journal-title":"J. Dairy. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1007\/s11745-017-4287-5","article-title":"Nutrient restriction increases circulating and hepatic ceramide in dairy cows displaying impaired insulin tolerance","volume":"52","author":"Davis","year":"2017","journal-title":"Lipids"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"958837","DOI":"10.3389\/fphys.2022.958837","article-title":"Ceramide metabolism associated with chronic dietary nutrient surplus and diminished insulin sensitivity in the liver, muscle, and adipose tissue of cattle","volume":"13","author":"Kenez","year":"2022","journal-title":"Front. Physiol."},{"key":"ref_45","first-page":"62","article-title":"Investigation on the relationship of insulin resistance and ketosis in dairy cows","volume":"5","author":"Xu","year":"2014","journal-title":"J. Vet. Sci. Technol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/s00580-016-2377-z","article-title":"The effect of subclinical ketosis on indices of insulin sensitivity and selected metabolic variables in transition dairy cattle","volume":"26","author":"Youssef","year":"2017","journal-title":"Comp. Clin. Pathol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"7619","DOI":"10.3168\/jds.2018-16095","article-title":"Invited review: Sphingolipid biology in the dairy cow: The emerging role of ceramide","volume":"102","author":"McFadden","year":"2019","journal-title":"J. Dairy. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1321597","DOI":"10.3389\/fimmu.2023.1321597","article-title":"Ceramide on the road to insulin resistance and immunometabolic disorders in transition dairy cows: Driver or passenger?","volume":"14","author":"Zhao","year":"2024","journal-title":"Front. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"106480","DOI":"10.1016\/j.domaniend.2020.106480","article-title":"Somatotropin increases plasma ceramide in relation to enhanced milk yield in cows","volume":"74","author":"Davis","year":"2021","journal-title":"Domest. Anim. Endocrinol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3428","DOI":"10.3168\/jds.2017-13983","article-title":"Hot topic: Ceramide inhibits insulin sensitivity in primary bovine adipocytes","volume":"101","author":"Rico","year":"2018","journal-title":"J. Dairy. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.cmet.2012.04.002","article-title":"A Ceramide-Centric View of Insulin Resistance","volume":"15","author":"Chavez","year":"2012","journal-title":"Cell Metab."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.2337\/diabetes.50.5.1126","article-title":"Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity during the progression to Type 2 diabetes in rhesus monkeys","volume":"50","author":"Hotta","year":"2001","journal-title":"Diabetes"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/S0014-5793(01)02960-X","article-title":"Adiponectin gene expression is inhibited by \u03b2-adrenergic stimulation via protein kinase A in 3T3-L1 adipocytes","volume":"507","author":"Fasshauer","year":"2001","journal-title":"FEBS Lett."},{"key":"ref_54","first-page":"182","article-title":"Comparison of adiponectin levels and some metabolic parameters in dairy cows with subclinical and clinical ketosis","volume":"74","author":"Akgul","year":"2018","journal-title":"Med. Weter.-Vet. Med.-Sci. Pract."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"806","DOI":"10.3168\/jds.2017-13752","article-title":"Short communication: The association of adiponectin and leptin concentrations with prepartum dietary energy supply, parity, body condition, and postpartum hyperketonemia in transition dairy cows","volume":"101","author":"Mann","year":"2018","journal-title":"J. Dairy. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.cimid.2013.10.007","article-title":"Adiponectin links adipose tissue function and monocyte inflammatory responses during bovine metabolic stress","volume":"37","author":"Kabara","year":"2014","journal-title":"Comp. Immunol. Microbiol. Infect. Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1038\/90984","article-title":"The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity","volume":"7","author":"Yamauchi","year":"2001","journal-title":"Nat. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1038\/nature21714","article-title":"Structural insights into adiponectin receptors suggest ceramidase activity","volume":"544","author":"Sounier","year":"2017","journal-title":"Nature"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"16802","DOI":"10.1038\/s41598-020-73912-5","article-title":"Neutral sphingomyelinase 2 regulates inflammatory responses in monocytes\/macrophages induced by TNF-\u03b1","volume":"10","author":"Ahmad","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbamcr.2003.10.002","article-title":"Cycloserine and threo-dihydrosphingosine inhibit TNF-\u03b1-induced cytotoxicity: Evidence for the importance of de novo ceramide synthesis in TNF-\u03b1 signaling","volume":"1643","author":"Meyer","year":"2003","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"304","DOI":"10.3389\/fncel.2015.00304","article-title":"Tissue-type plasminogen activator is a neuroprotectant in the central nervous system","volume":"9","author":"Yepes","year":"2015","journal-title":"Front. Cell. Neurosci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1194\/jlr.M074518","article-title":"Adipocyte mTORC1 deficiency promotes adipose tissue inflammation and NLRP3 inflammasome activation via oxidative stress and de novo ceramide synthesis","volume":"58","author":"Chimin","year":"2017","journal-title":"J. Lipid Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1111\/jnc.14225","article-title":"Activation of the NLRP3 inflammasome in microglia: The role of ceramide","volume":"143","author":"Scheiblich","year":"2017","journal-title":"J. Neurochem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/nm.2279","article-title":"The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance","volume":"17","author":"Vandanmagsar","year":"2011","journal-title":"Nat. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3466","DOI":"10.1172\/JCI42845","article-title":"Weight loss and lipolysis promote a dynamic immune response in murine adipose tissue","volume":"120","author":"Kosteli","year":"2010","journal-title":"J. Clin. Investig."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"10009","DOI":"10.3168\/jds.2016-11552","article-title":"Adipose tissue remodeling in late-lactation dairy cows during feed-restriction-induced negative energy balance","volume":"99","author":"Contreras","year":"2016","journal-title":"J. Dairy. Sci."},{"key":"ref_67","doi-asserted-by":"crossref","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":"ref_68","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.rvsc.2016.09.015","article-title":"Inflammatory biomarkers are associated with ketosis in periparturient Holstein cows","volume":"109","author":"Abuajamieh","year":"2016","journal-title":"Res. Vet. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2473","DOI":"10.3168\/jds.2021-21089","article-title":"Free fatty acids promote degranulation of azurophil granules in neutrophils by inducing production of NADPH oxidase-derived reactive oxygen species in cows with subclinical ketosis","volume":"105","author":"Song","year":"2022","journal-title":"J. Dairy. Sci."},{"key":"ref_70","doi-asserted-by":"crossref","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":"ref_71","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.14202\/vetworld.2021.1572-1578","article-title":"Comparative evaluation of cytokine and acute-phase protein concentrations in sera of dairy cows with subclinical and clinical ketosis as a different view of the causes of the disease","volume":"14","author":"Brodzki","year":"2021","journal-title":"Vet. World"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"104308","DOI":"10.1016\/j.jprot.2021.104308","article-title":"Characterization of the liver proteome in dairy cows experiencing negative energy balance at early lactation","volume":"246","author":"Swartz","year":"2021","journal-title":"J. Proteom."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.theriogenology.2015.02.006","article-title":"Inflammatory cytokines and acute-phase proteins concentrations in the peripheral blood and uterus of cows that developed endometritis during early postpartum","volume":"84","author":"Brodzki","year":"2015","journal-title":"Theriogenology"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.rvsc.2005.06.003","article-title":"Plasma malonaldehyde (MDA) and total antioxidant status (TAS) during lactation in dairy cows","volume":"80","author":"Castillo","year":"2006","journal-title":"Res. Vet. Sci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.tvjl.2004.02.001","article-title":"Oxidative status during late pregnancy and early lactation in dairy cows","volume":"169","author":"Castillo","year":"2005","journal-title":"Vet. J."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"9184","DOI":"10.3168\/jds.2016-11219","article-title":"\u03b2-Hydroxybutyrate induces bovine hepatocyte apoptosis via an ROS-p38 signaling pathway","volume":"99","author":"Song","year":"2016","journal-title":"J. Dairy. Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1292\/jvms.18-0777","article-title":"Increased serum malondialdehyde concentration in cows with subclinical ketosis","volume":"81","author":"Senoh","year":"2019","journal-title":"J. Vet. Med. Sci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"11369","DOI":"10.1074\/jbc.272.17.11369","article-title":"Direct Effect of ceramide on the mitochondrial electron transport chain leads to generation of reactive oxygen species: Role of mitochondrial glutathione","volume":"272","author":"Colell","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.1096\/fj.99-1028com","article-title":"GD3 ganglioside directly targets mitochondria in a bcl-2-controlled fashion","volume":"14","author":"Rippo","year":"2000","journal-title":"FASEB J."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"24154","DOI":"10.1074\/jbc.272.39.24154","article-title":"Direct inhibition of mitochondrial respiratory chain complex iii by cell-permeable ceramide","volume":"272","author":"Gudz","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"R2059","DOI":"10.1152\/ajpregu.00335.2007","article-title":"HIF-1\u03b1 in endurance training: Suppression of oxidative metabolism","volume":"293","author":"Mason","year":"2007","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"E1118","DOI":"10.1152\/ajpendo.00435.2007","article-title":"Hypoxia is a potential risk factor for chronic inflammation and adiponectin reduction in adipose tissue of ob\/ob and dietary obese mice","volume":"293","author":"Ye","year":"2007","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"E333","DOI":"10.1152\/ajpendo.90760.2008","article-title":"Role of hypoxia in obesity-induced disorders of glucose and lipid metabolism in adipose tissue","volume":"296","author":"Yin","year":"2009","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1016\/j.apsb.2021.10.001","article-title":"Disruption of adipocyte HIF-1\u03b1 improves atherosclerosis through the inhibition of ceramide generation","volume":"12","author":"Wang","year":"2022","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"10554","DOI":"10.3168\/jds.2019-16706","article-title":"Hepatic nuclear factor kappa B signaling pathway and NLR family pyrin domain containing 3 inflammasome is over-activated in ketotic dairy cows","volume":"102","author":"Shen","year":"2019","journal-title":"J. Dairy. Sci."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"796494","DOI":"10.3389\/fvets.2021.796494","article-title":"Differentiation of subclinical ketosis and liver function test indices in adipose tissues associated with hyperketonemia in postpartum dairy cattle","volume":"8","author":"Mohsin","year":"2021","journal-title":"Front. Vet. Sci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"11718","DOI":"10.3168\/jds.2019-16873","article-title":"Insulin signaling and insulin response in subcutaneous and retroperitoneal adipose tissue in Holstein cows during the periparturient period","volume":"102","author":"Ruda","year":"2019","journal-title":"J. Dairy. Sci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"3441","DOI":"10.3168\/jds.2013-7296","article-title":"Inflammation- and lipid metabolism-related gene network expression in visceral and subcutaneous adipose depots of Holstein cows","volume":"97","author":"Ji","year":"2014","journal-title":"J. Dairy. Sci."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"4514","DOI":"10.3168\/jds.2011-4145","article-title":"Hormone-sensitive lipase protein expression and extent of phosphorylation in subcutaneous and retroperitoneal adipose tissues in the periparturient dairy cow","volume":"94","author":"Locher","year":"2011","journal-title":"J. Dairy. Sci."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Leung, Y.H., Christiane, B.S., Koch, C., Scheu, T., Meyer, U., D\u00e4nicke, S., Huber, K., and Ken\u00e9z, \u00c1. (2020). Sphingolipid profiling reveals different extent of ceramide accumulation in bovine retroperitoneal and subcutaneous adipose tissues. 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