Articles | Volume 69, issue 3
https://doi.org/10.5194/aab-69-517-2026
© Author(s) 2026. This work is distributed under
the Creative Commons Attribution 4.0 License.
the Creative Commons Attribution 4.0 License.
https://doi.org/10.5194/aab-69-517-2026
© Author(s) 2026. This work is distributed under
the Creative Commons Attribution 4.0 License.
the Creative Commons Attribution 4.0 License.
Metabolic, adipokine (irisin, spexin, visfatin), and ER stress (GRP78) responses in multiparous Brown Swiss cows: a multivariate approach across physiological stages and body condition scores
Gökşad Cemil Kotan
Alaca Avni Çelik Vocational School, Department of Veterinary Medicine, Hitit University, Çorum, 19000, Türkiye
Şeyma Aydemir
Alaca Avni Çelik Vocational School, Department of Veterinary Medicine, Hitit University, Çorum, 19000, Türkiye
Bülent Bayraktar
CORRESPONDING AUTHOR
Faculty of Health Sciences, Department of Physiotherapy and Rehabilitation, Bayburt University, Bayburt, 69000, Türkiye
Cited articles
Adewuyi, A. A., Gruys, E., and van Eerdenburg, F. J.: Non-esterified fatty acids (NEFA) in dairy cattle: a review, Vet. Q., 27, 117–126, 2005.
AOAC International: Official methods of analysis of AOAC International, 20th edn., AOAC International, Gaithersburg, MD, ISBN 978-0-935584-87-5, 2016.
Bayraktar, B.: Endokrin Sistem, in: Sağlık Bilimleri İçin Fizyoloji, edited by: Taşkın, E. and Kocahan, S., Akademisyen Kitabevi, Ankara, Türkiye, 239–270, ISBN: 978-625-7795-60-9, 2020.
Bayraktar, B. and Genç, M.: The effect of change in body condition score at different stages of pregnancy on serum apelin-36 hormone levels in Simmental cattle, J. Anim. Vet. Adv., 20, 81–85, 2021.
Bayraktar, B., Tekce, E., Aksakal, V., Takma, Ç., Bayraktar, F. G., and Şengül, B.: Effects of race, gender, body condition score and pregnancy on serum Apelin levels in ewe, J. Agr. Sci., 26, 363–372, https://doi.org/10.15832/ankutbd.526907, 2020.
Boström, P., Wu, J., Jedrychowski, M. P., Korde, A., Ye, L., Lo, J. C., and Spiegelman, B. M.: A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis, Nature, 481, 463–468, https://doi.org/10.1038/nature10777, 2012.
Butler, W. R. and Smith, R. D.: Interrelationships between energy balance and postpartum reproductive function in dairy cattle, J. Dairy Sci., 72, 767–783, https://doi.org/10.3168/jds.S0022-0302(89)79169-4, 1989.
Byun, J. H., Lebeau, P. F., Trink, J., Uppal, N., Lanktree, M. B., Krepinsky, J. C., and Austin, R. C.: Endoplasmic reticulum stress as a driver and therapeutic target for kidney disease, Nat. Rev. Nephrol., 21, 299–313, https://doi.org/10.1038/s41581-025-00938-1, 2025.
Cameron, K., Nguyen, A. L., Gibson, D. J., Ward, M. G., Sparrow, M. P., and Gibson, P. R.: Albumin and its role in inflammatory bowel disease: the old, the new, and the future, J. Gastroenterol. Hepatol., 40, 808–820, https://doi.org/10.1111/jgh.16895, 2025.
Chen, Y., He, M., Lei, M. M., Ko, W. K., Lin, C., Bian, Z., and Wong, A. O.: Mouse spexin: (III) differential regulation by glucose and insulin in glandular stomach and functional implication in feeding control, Front. Endocrinol., 12, 681648, https://doi.org/10.3389/fendo.2021.681648, 2021.
Chen, X., Yan, Y., Dong, J., Zhang, H., Zhang, Y., Gao, F., Ye, X., and Sun, C.: Spexin-mediated dietary adaptation in Siniperca chuatsi: molecular characterisation and functional insights into FABP2 interaction, Animals, 15, 2944, https://doi.org/10.3390/ani15202944, 2025.
Çolak, M., Toy, H., and Kilic, N.: Laktasyonun farklı dönemlerindeki ineklerde bazı adipokinler ile metabolik parametreler arasındaki ilişkilerin incelenmesi, Eurasian J. Vet. Sci., 35, 31–38, 2019.
Cozzi, G., Ravarotto, L., Gottardo, F., Stefani, A. L., Contiero, B., Moro, L., and Dalvit, P.: Reference values for blood parameters in Holstein dairy cows: Effects of parity, stage of lactation, and season of production, J. Dairy Sci., 94, 3895–3901, 2011.
Crampton, E. W. and Maynard, L. A.: The relation of cellulose and lignin content to the nutritive value of animal feeds, J. Nutr., 15, 383–395, https://doi.org/10.1093/jn/15.4.383, 1938.
Dajnowska, A., Osiak-Wicha, C., Piech, M., Muszyński, S., Tomaszewska, E., Ropka-Molik, K., and Arciszewski, M. B.: Immunoexpression of Spexin in Selected Segments of the Bovine (Bos taurus taurus) Gastrointestinal Tract, Animals, 13, 3789, https://doi.org/10.3390/ani13243789, 2023.
De Koster, J., Van Eetvelde, M., Hermans, K., Van Den Broeck, W., Hostens, M., and Opsomer, G.: Limitations of glucose tolerance tests in the assessment of peripheral tissue insulin sensitivity during pregnancy and lactation in dairy heifers, J. Dairy Sci., 100, 2381–2387, https://doi.org/10.3168/jds.2016-11792, 2017.
Edmonson, A. J., Lean, I. J., Weaver, L. D., Farver, T., and Webster, G.: A body condition scoring chart for Holstein dairy cows, J. Dairy Sci., 72, 68–78, https://doi.org/10.3168/jds.s0022-0302(89)79081-0, 1989.
Eğritağ, H. E., Merhan, O., Bozukluhan, K., Varol, K., and Atcalı, T.: Investigation of serum leptin, ghrelin, irisin, insulin levels and their correlations in cattle with subclinical ketosis, Vet. J. Mehmet Akif Ersoy Univ., 7, 223–228, https://doi.org/10.24880/maeuvfd.1202455, 2022.
Elsherbiny, H., Alnasser, S. M., Aref, M., ElSheikh, E., El-Sayed, S. F., El-Malkey, N. F., and Salem, G. A.: Spexin peptide ameliorates renal injury in diabetic nephropathy rat model via modulation of metabolic, oxidative, inflammatory, and apoptotic dysregulations, J. Physiol. Biochem., 1–16, https://doi.org/10.1007/s13105-025-01092-9, 2025.
Ferguson, J. D., Galligan, D. T., and Thomsen, N.: Principal descriptors of body condition score in Holstein cows, J. Dairy Sci., 77, 2695–2703, https://doi.org/10.3168/jds.S0022-0302(94)77212-X, 1994.
Goering, H. K. and Van Soest, P. J.: Forage fiber analyses (apparatus, reagents, procedures, and some applications), Agriculture Handbook No. 379, U.S. Government Printing Office, Washington, DC, 1970.
Goselink, R. M., Schonewille, J. T., van Duinkerken, G., and Hendriks, W. H.: Physical exercise prepartum to support metabolic adaptation in the transition period of dairy cattle: A proof of concept, J. Anim. Physiol. An. N., 104, 790–801, https://doi.org/10.1111/jpn.13330, 2020.
Gregor, A. N., Delerive, P., Cuenoud, B., Monnard, I., Redeuil, K., Harding, C. O., and Gillingham, M. B.: D-BHB supplementation before moderate-intensity exercise suppresses lipolysis and selectively blunts exercise-induced long-chain acylcarnitine increase in pilot study of patients with long-chain fatty acid oxidation disorders, Mol. Genet. Metab., 144, 109070, https://doi.org/10.1016/j.ymgme.2025.109070, 2025.
Harooni, E. and Radmehr, V.: Spexin as a metabolic regulatory peptide in liver, adipose tissue, skeletal muscle, and pancreas: evidence from animal models and human studies, Horm. Mol. Biol. Clin. In., 46, 177–182, 2025.
Ji, X., Liu, N., Wang, Y., Ding, K., Huang, S., and Zhang, C.: Pregnancy toxemia in ewes: a review of molecular metabolic mechanisms and management strategies, Metabolites, 13, 149, https://doi.org/10.3390/metabo13020149, 2023.
Jeong, B., Kim, K. K., Lee, T. H., Kim, H. R., Park, B. S., Park, J. W., and Lee, B. J.: Spexin regulates hypothalamic leptin action on feeding behavior, Biomolecules, 12, 236, https://doi.org/10.3390/biom12020236, 2022.
Kaneko, J. J., Harvey, J. W., and Bruss, M. L.: Clinical Biochemistry of Domestic Animals, 6th edn., Academic Press, San Diego, CA, ISBN 978-0-12-370491-7, 2008.
Kang, D., Lungu, S. E., Danso, F., Dzou, C. F., Chen, Y., Zheng, X., and Zhou, G.: Animal health and nutrition: Metabolic disorders in cattle and improvement strategies, Front Vet. Sci., 12, 1470391, https://doi.org/10.3389/fvets.2025.1470391, 2025.
Kessler, E. C., Gross, J. J., Bruckmaier, R. M., and Albrecht, C.: Cholesterol metabolism, transport, and hepatic regulation in dairy cows during transition and early lactation, J. Dairy Sci., 97, 5481–5490, 2014.
Kızıl, M., Rişvanlı, A., Abay, M., Şafak, T., Kılınç, M. A., Yılmaz, Ö., and Şeker, İ.: Effect of calf delivery mode on irisin, asprosin, leptin, adiponectin, and insulin-like growth factor-1 levels in dairy cattle and their calves, Pak. J. Zool., 55, 1527–1535, https://doi.org/10.17582/journal.pjz/20221031081040, 2023.
Kolodziejski, P. A., Pruszynska-Oszmalek, E., Micker, M., Skrzypski, M., Wojciechowicz, T., Szwarckopf, P., and Strowski, M. Z.: Spexin: A novel regulator of adipogenesis and fat tissue metabolism, Biochim. Biophys. Acta Mol. Cell Biol. Lipids, 1863, 1228–1236, https://doi.org/10.1016/j.bbalip.2018.08.001, 2018.
Komarnicki, P., Maciejewski, A., Musiałkiewicz, J., Czupińska, M., Mastorakos, G., Ruchała, M., and Gut, P.: Serum visfatin/eNAMPT as a biomarker in pancreatic and small intestine neuroendocrine tumors: a cross-sectional study and future perspectives, Cancers, 17, 2343, 2025.
Li, J., He, W., Wu, Q., Qin, Y., Luo, C., Dai, Z., and Cao, L.: Ketogenic diets and β-hydroxybutyrate in the prevention and treatment of diabetic kidney disease: current progress and future perspectives, BMC Nephrol., 26, 127, https://doi.org/10.1186/s12882-025-04019-0, 2025.
Lin, M., Mo, Y., Li, C. M., Liu, Y. Z., and Feng, X. P.: GRP78 as a potential therapeutic target in cancer treatment: An updated review of its role in chemoradiotherapy resistance of cancer cells, Med. Oncol., 42, 49, https://doi.org/10.1007/s12032-024-02586-0, 2025.
Liu, J., Dai, S., Shao, X., Wei, C., Dai, Z., Yang, P., Wang, Z., and Zhu, H.: Spexin mRNA profile and its response to different photoperiods in Chinese Yangzhou geese (Anas cygnoides), Front. Vet. Sci., 9, 961431, https://doi.org/10.3389/fvets.2022.961431, 2022.
Losacco, C., Pugliese, G., Forte, L., Tufarelli, V., Maggiolino, A., and De Palo, P.: Digital transition as a driver for sustainable tailor-made farm management: An up-to-date overview on precision livestock farming, Agriculture, 15, 1, https://doi.org/10.3390/agriculture15131383, 2025.
Luo, D., Fan, N., Zhang, X., Ngo, F. Y., Zhao, J., Zhao, W., and Rong, J.: Covalent inhibition of endoplasmic reticulum chaperone GRP78 disconnects the transduction of ER stress signals to inflammation and lipid accumulation in diet-induced obese mice, Elife, 11, e72182, https://doi.org/10.7554/eLife.72182, 2022.
Martinotti, S. and Ranzato, E.: Targeting the unfolded protein response with natural products: therapeutic potential in ER stress-related diseases, Int. J. Mol. Sci., 26, 8814, https://doi.org/10.3390/ijms26188814, 2025.
McFadden, J. W.: Lipid biology in the periparturient dairy cow: Contemporary perspectives, Animal, 14, s165–s175, 2020.
Mekuriaw, Y.: Negative energy balance and its implication on productive and reproductive performance of early lactating dairy cows, J. Appl. Anim. Res., 51, 220–228, https://doi.org/10.1080/09712119.2023.2176859, 2023.
Mikuła, R., Pruszyńska-Oszmałek, E., Pszczola, M., Rząsińska, J., Sassek, M., Nowak, K. W., and Kołodziejski, P. A.: Changes in metabolic and hormonal profiles during transition period in dairy cattle–the role of spexin, BMC Vet. Res., 17, 359, https://doi.org/10.1186/s12917-021-03069-4, 2021.
Ormazabal, P., Bastías-Pérez, M., Inestrosa, N. C., and Cisternas, P.: Adipokines at the metabolic–brain interface: therapeutic modulation by antidiabetic agents and natural compounds in Alzheimer's disease, Pharmaceuticals, 18, 1527, https://doi.org/10.3390/ph18101527, 2025.
Osorio, J. S., Trevisi, E., Ji, P., Drackley, J. K., Luchini, D., Bertoni, G., and Loor, J. J.: Biomarkers of inflammation, metabolism, and oxidative stress in blood, liver, and milk reveal a better immunometabolic status in peripartal cows supplemented with Smartamine M or MetaSmart, J. Dairy Sci., 97, 7437–7450, 2014.
Öztüfek, H., Bayraktar, B., Tekce, E., and Aksakal, V.: İrisin hormonu fizyolojisi ve fizyolojik sistemler üzerindeki etkisinin incelenmesi, in: Türkiye Vizyonu: Multidisipliner Çalışmalar, Ekin Yayınevi, 342–347, ISBN 978-605-327-870-2, 2019.
Potiris, A., Moustakli, E., Trismpioti, E., Drakaki, E., Mavrogianni, D., Matsas, A., and Stavros, S.: From inflammation to infertility: how oxidative stress and infections disrupt male reproductive health, Metabolites, 15, 267, https://doi.org/10.3390/metabo15040267, 2025.
Pruszynska-Oszmalek, E., Sassek, M., Szczepankiewicz, D., Nowak, K. W., and Kolodziejski, P. A.: Short-term administration of spexin in rats reduces obesity by affecting lipolysis and lipogenesis: an in vivo and in vitro study, Gen. Comp. Endocr., 299, 113615, https://doi.org/10.1016/j.ygcen.2020.113615, 2020.
Ratajczak-Pawłowska, A. E., Szymczak-Tomczak, A., Hryhorowicz, S., Zawada, A., Skoracka, K., Rychter, A. M., and Krela-Kaźmierczak, I.: Relationship of visfatin with obesity and osteoporosis in patients with inflammatory bowel disease: a narrative review, Front. Immunol., 16, 1533955, https://doi.org/10.3389/fimmu.2025.1533955, 2025.
Reverchon, M., Cornuau, M., Cloix, L., Rame, C., Guerif, F., Royere, D., and Dupont, J.: Visfatin is expressed in human granulosa cells: regulation by metformin through AMPK/SIRT1 pathways and its role in steroidogenesis, Mol. Hum. Reprod., 19, 313–326, https://doi.org/10.1093/molehr/gat002, 2013.
Ruan, H., Zhu, M., Liu, S. Y., Zou, L. J., and Li, S. S.: GRP78 dysregulation: A proposed molecular mechanism linking the tumor microenvironment to sepsis susceptibility in patients with cancer, Int. J. Mol. Med., 58, 1–25, https://doi.org/10.3892/ijmm.2026.5919, 2026.
Shi, R. and Gu, J.: The role of nicotinamide phosphoribosyltransferase in NAD+ synthesis, in: Biology of Nicotinamide Coenzymes: From Basic Science to Clinical Applications, Springer Nature Singapore, Singapore, 57–71, https://doi.org/10.1007/978-981-97-9877-3_6, 2025.
Slivinska, L., Shcherbatyi, A., Gutyj, B., Pundiak, T., Simonov, M., Leskiv, K., and Petryshak, S.: Metabolic profile of the blood of cows with microelement deficiency, Sci. Mess. LNU Vet. Med. Biotech., 27, 10–16, https://doi.org/10.32718/nvlvet11802, 2025.
Sosa-Higareda, M. and Beaufrère, H.: Diet type, fasting duration, and computed tomography hepatic attenuation influence postprandial plasma lipids, β-hydroxybutyric acid, glucose, and uric acid in bearded dragons (Pogona vitticeps), Am. J. Vet. Res., 86, https://doi.org/10.2460/ajvr.24.09.0252, 2025.
Sun, R., Jiang, X., Hao, Y., Li, Y., Bai, Y., Xia, C., and Song, Y.: Effect of body condition score loss during the transition period on metabolism, milk yield and health in Holstein cows, J. Vet. Res., 69, 91–99, https://doi.org/10.2478/jvetres-2025-0004, 2025.
Sun, X., Yu, Z., Xu, Y., Pu, S., and Gao, X.: The role of spexin in energy metabolism, Peptides, 164, 170991, https://doi.org/10.1016/j.peptides.2023.170991, 2023.
Tani, S., Imatake, K., Suzuki, Y., Yagi, T., and Takahashi, A.: Association of aerobic exercise habits with higher albumin-globulin ratio and lower cellular immune-inflammatory markers: implication of the preventive effect of aerobic exercise on atherosclerotic cardiovascular disease, Heart Vessels, 40, 509–522, https://doi.org/10.1007/s00380-024-02490-7, 2025.
Tran, A., He, W., Chen, J. T., and Belsham, D. D.: Spexin: its role, regulation, and therapeutic potential in the hypothalamus, Pharmacol Therapeut, 233, 108033, https://doi.org/10.1016/j.pharmthera.2021.108033, 2022.
Turk, R., Juretić, D., Gereš, D., Svetina, A., Turk, N., and Flegar-Meštrić, Z.: Influence of oxidative stress and metabolic adaptation on PON1 activity and MDA level in transition dairy cows, Anim. Reprod. Sci., 108, 98–106, https://doi.org/10.1016/j.anireprosci.2007.07.012, 2008.
Türkel, İ., Memi, G., and Yazgan, B.: Impact of spexin on metabolic diseases and inflammation: an updated minireview, Exp. Biol. Med., 247, 567–573, 2022.
Ünal, C. N., Keçeci, H., and Uztimür, M.: The effect of parity, lactation period, and milk yield on metabolic profile parameters in Holstein dairy cows, Etlik Vet. Mikrobiyol. Derg., 36, 107–114, https://doi.org/10.35864/evmd.1752756, 2026.
Van Den Top, A. M., Wensing, T., Geelen, M. J. H., Wentink, G. H., Van't Klooster, A. T., and Beynen, A. C.: Time trends of plasma lipids and enzymes synthesizing hepatic triacylglycerol during postpartum development of fatty liver in dairy cows, J. Dairy Sci., 78, 2208–2220, 1995.
Van Soest, P. J., Robertson, J. B., and Lewis, B. A.: Methods for dietary fiber, neutral detergent fiber, and nonstarch polysaccharides in relation to animal nutrition, J. Dairy Sci., 74, 3583–3597, https://doi.org/10.3168/jds.s0022-0302(91)78551-2, 1991.
Vietri, M., Miranda, M. R., Amodio, G., Ciaglia, T., Bertamino, A., Campiglia, P., and Moltedo, O.: The link between endoplasmic reticulum stress and lysosomal dysfunction under oxidative stress in cancer cells, Biomolecules, 15, 930, https://doi.org/10.3390/biom15070930, 2025.
Walewski, J. L., Ge, F., Lobdell IV, H., Levin, N., Schwartz, G. J., Vasselli, J. R., and Berk, P. D.: Spexin is a novel human peptide that reduces adipocyte uptake of long chain fatty acids and causes weight loss in rodents with diet‐induced obesity, Obesity, 22, 1643–1652, https://doi.org/10.1002/oby.20725, 2014.
Wang, F., Guo, Y., Su, X., and Cao, J.: Choline as a modulator of periparturient diseases in dairy cows, Vet. Sci., 12, 1016, https://doi.org/10.3390/vetsci12101016, 2025.
Xu, Q., Li, X., Ma, L., Loor, J. J., Coleman, D. N., Jia, H., and Li, X.: Adipose tissue proteomic analysis in ketotic or healthy Holstein cows in early lactation, J. Anim. Sci., 97, 2837–2849, 2019.
Yaprakci, Ö. and Akkuş, T.: Evaluation of nesfatin-1 levels in ewes with pregnancy toxemia, Rev. Cient. Fac. Vet., 35, https://doi.org/10.52973/rcfcv-e35712, 2025.
Zheng, Y., He, J., Yang, D., Yuan, M., Liu, S., Dai, F., and Cheng, Y.: Irisin reduces the abnormal reproductive and metabolic phenotypes of PCOS by regulating the activity of brown adipose tissue in mice, Biol. Reprod., 107, 1046–1058, 2022.
Short summary
This study investigates metabolic adaptation, novel hormones, and cellular stress in dairy cows across pregnancy and lactation stages with different body condition scores. Results show that the dry period and early lactation represent critical metabolic stress points with elevated cellular stress and fat mobilization. Monitoring these novel biomarkers provides practical insights for optimizing transition-period nutritional strategies and herd health management.
This study investigates metabolic adaptation, novel hormones, and cellular stress in dairy cows...