FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / BMC Vet Res / Revitalizing equine metabolism: how SHBG improves mitochondr...
BMC veterinary research2025; 21(1); 620; doi: 10.1186/s12917-025-05033-y

Revitalizing equine metabolism: how SHBG improves mitochondrial function and reduces inflammation.

Abstract: Equine metabolic syndrome (EMS) is associated with chronic low-grade inflammation, disruptions in mitochondrial dynamics and function, and an increased risk of developing laminitis. Recent research has highlighted that reduced levels of sex hormone-binding globulin (SHBG) in the bloodstream are linked to higher susceptibility to obesity, insulin resistance, and diabetes, potentially contributing to broader metabolic imbalances. This study aimed to evaluate whether exogenously administered SHBG could protect adipose-derived stem cells from horses affected by EMS (EqASC) against mitochondrial dysfunction and inflammatory activation. Following treatment with 50 nM of SHBG, analyses were conducted to assess cell viability, mitochondrial metabolism and dynamics, as well as the expression of inflammatory and anti-inflammatory markers. Results showed that SHBG significantly enhanced mitochondrial flexibility, as indicated by the upregulation of MFN-1, PARKIN, and PINK genes. SHBG also positively influenced the expression of genes related to mitoribosomes and the mitochondrial oxidative phosphorylation (OXPHOS) system. In addition, SHBG treatment markedly reduced EMS-induced inflammation by decreasing pro-inflammatory cytokines such as IL-1β as well as IL-6 and boosting anti-inflammatory cytokines gene expression (IL-10 and IL-13). Our findings suggest that SHBG exerts beneficial effects on the metabolic function of stem cells affected by EMS and holds promise as a potential therapeutic agent in the development of effective treatment strategies for this condition. [Image: see text] The online version contains supplementary material available at 10.1186/s12917-025-05033-y.
Get Full Text
Publication Date: 2025-10-21 PubMed ID: 41121214PubMed Central: PMC12539183DOI: 10.1186/s12917-025-05033-yGoogle Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

Overview

  • This study investigates how sex hormone-binding globulin (SHBG) treatment can improve mitochondrial function and reduce inflammation in stem cells derived from horses with equine metabolic syndrome (EMS), a condition associated with obesity, insulin resistance, and inflammation.
  • The research highlights SHBG’s potential to restore cell metabolic health and modulate inflammatory responses, offering a promising therapeutic approach for EMS.

Introduction to Equine Metabolic Syndrome (EMS)

  • EMS is a common condition in horses characterized by:
    • Chronic low-grade inflammation
    • Dysfunction in mitochondrial dynamics and function
    • Increased risk of laminitis, a painful hoof disease
  • Associated metabolic disturbances include obesity, insulin resistance, and predisposition to diabetes.
  • SHBG, a protein that binds sex hormones in the bloodstream, is found at reduced levels in individuals with metabolic imbalances.

Rationale for SHBG Treatment

  • Decreased SHBG has been linked to higher risks of metabolic disorders such as obesity and diabetes.
  • This study hypothesized that administering SHBG externally might protect and improve cellular function in EMS-affected cells.
  • Specifically, the focus was on adipose-derived stem cells from EMS horses (EqASC) as a model for investigating mitochondrial and inflammatory status.

Methodology

  • Adipose-derived stem cells isolated from horses diagnosed with EMS were cultured.
  • Cells were treated with 50 nM concentrations of SHBG.
  • Post-treatment analyses included:
    • Cell viability assessments to ensure treatments were not toxic
    • Measurement of mitochondrial metabolism and dynamics markers
    • Gene expression profiling of inflammatory and anti-inflammatory cytokines

Key Findings

  • Mitochondrial Function Improvements:
    • SHBG increased mitochondrial flexibility, vital for adapting to cellular energy demands.
    • Upregulation of genes related to mitochondrial dynamics:
      • MFN-1 (Mitofusin-1): promotes mitochondrial fusion
      • PARKIN and PINK1: involved in mitophagy, the removal of damaged mitochondria
    • Enhanced expression of genes related to mitoribosomes and the mitochondrial oxidative phosphorylation system, which are essential for energy production.
  • Reduction of Inflammation:
    • SHBG treatment decreased expression of pro-inflammatory cytokines:
      • IL-1β
      • IL-6
    • Increased expression of anti-inflammatory cytokine genes:
      • IL-10
      • IL-13

Implications of the Research

  • The findings suggest that SHBG has a protective role in counteracting EMS-related mitochondrial dysfunction and inflammation.
  • By improving mitochondrial health and reducing inflammation, SHBG could help restore normal metabolism in stem cells affected by EMS.
  • This lays the groundwork for considering SHBG as a therapeutic agent for managing EMS and potentially other metabolic disorders.
  • Future therapies could focus on modulating SHBG levels to improve equine metabolic health and reduce complications such as laminitis.

Overall Conclusion

  • The study provides strong evidence that SHBG administration improves key cellular functions related to energy metabolism and inflammation in EMS-affected equine stem cells.
  • These beneficial effects of SHBG support its potential use in developing novel treatments aimed at alleviating the pathological features of EMS.

Cite This Article

APA
Bourebaba N, Domagała J, Bourebaba L. (2025). Revitalizing equine metabolism: how SHBG improves mitochondrial function and reduces inflammation. BMC Vet Res, 21(1), 620. https://doi.org/10.1186/s12917-025-05033-y

Publication

BMC veterinary research
ISSN: 1746-6148
NlmUniqueID: 101249759
Country: England
Language: English
Volume: 21
Issue: 1
Pages: 620
PII: 620

Researcher Affiliations

Bourebaba, Nabila
  • Department of Experimental Biology, Faculty of Biology and Animal Science, Wrocław University of Environmental and Life Sciences, Norwida 27B, Wrocław, 50-375, Poland. nabila.bourebaba@upwr.edu.pl.
Domagała, Justyna
  • Department of Internal Medicine and Clinic of Diseases of Horses, Dogs and Cats, Faculty of Veterinary Medicine, Wrocław University of Environmental and Life Sciences, Grunwaldzki Sq. 47, Bldg. B2, Room 1-207a, Wrocław, 50-366, Poland.
Bourebaba, Lynda
  • Department of Experimental Biology, Faculty of Biology and Animal Science, Wrocław University of Environmental and Life Sciences, Norwida 27B, Wrocław, 50-375, Poland. lynda.bourebaba@upwr.edu.pl.

Conflict of Interest Statement

Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

References

This article includes 74 references
  1. Frank N. Equine metabolic syndrome. Vet Clin North Am Equine Pract. 2011;27(1):73–92. 10.1016/j.cveq.2010.12.004.
    doi: 10.1016/j.cveq.2010.12.004pubmed: 21392655google scholar: lookup
  2. Ramiro E. Metabolic Syndrome, Equine. InClinical Veterinary Advisor. Elsevier; 2012. pp. 357–358. 10.1016/B978-1-4160-9979-6.00490-6.
  3. Freeman AM, Acevedo LA, Pennings N. Insulin Resistance. InStatPearls. StatPearls Publishing; 2024. Accessed 7 Jul 2024. http://www.ncbi.nlm.nih.gov/books/NBK507839/.
    pubmed: 29939616
  4. Sergi D, Naumovski N, Heilbronn LK, et al. Mitochondrial (dys)function and insulin resistance: from pathophysiological molecular mechanisms to the impact of diet. Front Physiol. 2019;10:532. 10.3389/fphys.2019.00532.
    doi: 10.3389/fphys.2019.00532pmc: PMC6510277pubmed: 31130874google scholar: lookup
  5. Chandrasekaran P, Weiskirchen R. Cellular and molecular mechanisms of insulin resistance. Curr Tissue Microenviron Rep. 2024;5(3):79–90. 10.1007/s43152-024-00056-3.
    doi: 10.1007/s43152-024-00056-3google scholar: lookup
  6. Das S, Hajnóczky N, Antony AN, et al. Mitochondrial morphology and dynamics in hepatocytes from normal and ethanol-fed rats. Pflugers Arch - Eur J Physiol. 2012;464(1):101–9. 10.1007/s00424-012-1100-4.
    doi: 10.1007/s00424-012-1100-4pmc: PMC3799820pubmed: 22526459google scholar: lookup
  7. Keaney JF, Larson MG, Vasan RS, et al. Obesity and systemic oxidative stress: clinical correlates of oxidative stress in the Framingham study. ATVB. 2003;23(3):434–9. 10.1161/01.ATV.0000058402.34138.11.
    doi: 10.1161/01.ATV.0000058402.34138.11pubmed: 12615693google scholar: lookup
  8. Kostis J, Sanders M. The association of heart failure with insulin resistance and the development of type 2 diabetes. Am J Hypertens. 2005;18(5):731–7. 10.1016/j.amjhyper.2004.11.038.
    doi: 10.1016/j.amjhyper.2004.11.038pubmed: 15882558google scholar: lookup
  9. Bhatti JS, Bhatti GK, Reddy PH. Mitochondrial dysfunction and oxidative stress in metabolic disorders — a step towards mitochondria based therapeutic strategies. Biochimica et Biophysica Acta (BBA). 2017;1863(5):1066–77. 10.1016/j.bbadis.2016.11.010.
    doi: 10.1016/j.bbadis.2016.11.010pmc: PMC5423868pubmed: 27836629google scholar: lookup
  10. González P, Lozano P, Ros G, Solano F. Hyperglycemia and oxidative stress: an integral, updated and critical overview of their metabolic interconnections. IJMS. 2023;24(11):9352. 10.3390/ijms24119352.
    doi: 10.3390/ijms24119352pmc: PMC10253853pubmed: 37298303google scholar: lookup
  11. Cojocaru KA, Luchian I, Goriuc A, et al. Mitochondrial dysfunction, oxidative stress, and therapeutic strategies in diabetes, obesity, and cardiovascular disease. Antioxidants. 2023;12(3):658. 10.3390/antiox12030658.
    doi: 10.3390/antiox12030658pmc: PMC10045078pubmed: 36978905google scholar: lookup
  12. Ding XW, Robinson M, Li R, Aldhowayan H, Geetha T, Babu JR. Mitochondrial dysfunction and beneficial effects of mitochondria-targeted small peptide SS-31 in Diabetes mellitus and Alzheimer’s disease. Pharmacol Res. 2021;171:105783. 10.1016/j.phrs.2021.105783.
    doi: 10.1016/j.phrs.2021.105783pubmed: 34302976google scholar: lookup
  13. Leguisamo NM, Lehnen AM, Machado UF, et al. GLUT4 content decreases along with insulin resistance and high levels of inflammatory markers in rats with metabolic syndrome. Cardiovasc Diabetol. 2012;11(1):100. 10.1186/1475-2840-11-100.
    doi: 10.1186/1475-2840-11-100pmc: PMC3439702pubmed: 22897936google scholar: lookup
  14. Xu X, Pang Y, Fan X. Mitochondria in oxidative stress, inflammation and aging: from mechanisms to therapeutic advances. Sig Transduct Target Ther. 2025;10(1):190. 10.1038/s41392-025-02253-4.
    doi: 10.1038/s41392-025-02253-4pmc: PMC12159213pubmed: 40500258google scholar: lookup
  15. Mitsuyoshi H, Itoh Y, Sumida Y, et al. Evidence of oxidative stress as a cofactor in the development of insulin resistance in patients with chronic hepatitis C. Hepatol Res. 2008;38(4):348–53. 10.1111/j.1872-034X.2007.00280.x.
    doi: 10.1111/j.1872-034X.2007.00280.xpubmed: 18021228google scholar: lookup
  16. Prasun P. Mitochondrial dysfunction in metabolic syndrome. Biochimica et Biophysica Acta (BBA). 2020;1866(10):165838. 10.1016/j.bbadis.2020.165838.
    doi: 10.1016/j.bbadis.2020.165838pubmed: 32428560google scholar: lookup
  17. Zak A, Siwinska N, Elzinga S, et al. Effects of equine metabolic syndrome on inflammation and acute-phase markers in horses. Domest Anim Endocrinol. 2020;72:106448. 10.1016/j.domaniend.2020.106448.
    doi: 10.1016/j.domaniend.2020.106448pubmed: 32247989google scholar: lookup
  18. Megha KB, Joseph X, Akhil V, Mohanan PV. Cascade of immune mechanism and consequences of inflammatory disorders. Phytomedicine. 2021;91:153712. 10.1016/j.phymed.2021.153712.
    doi: 10.1016/j.phymed.2021.153712pmc: PMC8373857pubmed: 34511264google scholar: lookup
  19. Smieszek A, Kornicka K, Szłapka-Kosarzewska J, et al. Metformin increases proliferative activity and viability of multipotent stromal stem cells isolated from adipose tissue derived from horses with Equine Metabolic Syndrome. Cells. 2019;8(2):80. 10.3390/cells8020080.
    doi: 10.3390/cells8020080pmc: PMC6406832pubmed: 30678275google scholar: lookup
  20. Marycz K, Kornicka K, Basinska K, Czyrek A. Equine Metabolic syndrome affects viability, senescence, and stress factors of equine adipose-derived mesenchymal stromal stem cells: new insight into EqASCs isolated from EMS horses in the context of their aging. Oxid Med Cell Longev. 2016;2016:1–17. 10.1155/2016/4710326.
    doi: 10.1155/2016/4710326pmc: PMC4670679pubmed: 26682006google scholar: lookup
  21. Makki K, Froguel P, Wolowczuk I. Adipose tissue in obesity-related inflammation and insulin resistance: cells, cytokines, and chemokines. ISRN Inflamm. 2013;2013:1–12. 10.1155/2013/139239.
    doi: 10.1155/2013/139239pmc: PMC3881510pubmed: 24455420google scholar: lookup
  22. Yao J, Wu D, Qiu Y. Adipose tissue macrophage in obesity-associated metabolic diseases. Front Immunol. 2022;13:977485. 10.3389/fimmu.2022.977485.
    doi: 10.3389/fimmu.2022.977485pmc: PMC9478335pubmed: 36119080google scholar: lookup
  23. Kornicka-Garbowska K, Bourebaba L, Röcken M, Marycz K. Inhibition of protein tyrosine phosphatase improves mitochondrial bioenergetics and dynamics, reduces oxidative stress, and enhances adipogenic differentiation potential in metabolically impaired progenitor stem cells. Cell Commun Signal. 2021;19(1):106. 10.1186/s12964-021-00772-5.
    doi: 10.1186/s12964-021-00772-5pmc: PMC8565043pubmed: 34732209google scholar: lookup
  24. Bourebaba N, Ngo T, Śmieszek A, Bourebaba L, Marycz K. Sex hormone binding globulin as a potential drug candidate for liver-related metabolic disorders treatment. Biomed Pharmacother. 2022;153:113261. 10.1016/j.biopha.2022.113261.
    doi: 10.1016/j.biopha.2022.113261pubmed: 35738176google scholar: lookup
  25. Basualto-Alarcón C, Llanos P, García-Rivas G, et al. Classic and novel sex hormone binding globulin effects on the cardiovascular system in men. Int J Endocrinol. 2021;2021:1–13. 10.1155/2021/5527973. Ferlin A, ed.
    doi: 10.1155/2021/5527973pmc: PMC8318754pubmed: 34335746google scholar: lookup
  26. Le TN, Nestler JE, Strauss JF, Wickham EP. Sex hormone-binding globulin and type 2 diabetes mellitus. Trends Endocrinol Metab. 2012;23(1):32–40. 10.1016/j.tem.2011.09.005.
    doi: 10.1016/j.tem.2011.09.005pmc: PMC3351377pubmed: 22047952google scholar: lookup
  27. Zhang H, Qiu W, Zhou P, et al. Obesity is associated with SHBG levels rather than blood lipid profiles in PCOS patients with insulin resistance. BMC Endocr Disord. 2024;24(1):254. 10.1186/s12902-024-01789-w.
    doi: 10.1186/s12902-024-01789-wpmc: PMC11587586pubmed: 39587600google scholar: lookup
  28. Ottarsdottir K, Hellgren M, Bock D, Nilsson AG, Daka B. Longitudinal associations between sex hormone-binding globulin and insulin resistance. Endocr Connect. 2020;9(5):418–25. 10.1530/EC-20-0141.
    doi: 10.1530/EC-20-0141pmc: PMC7274552pubmed: 32427568google scholar: lookup
  29. Simó R, Barbosa-Desongles A, Lecube A, Hernandez C, Selva DM. Potential role of tumor necrosis factor-α in downregulating sex hormone-binding globulin. Diabetes. 2012;61(2):372–82. 10.2337/db11-0727.
    doi: 10.2337/db11-0727pmc: PMC3266423pubmed: 22210320google scholar: lookup
  30. Szybiak-Skora W, Cyna W, Lacka K. New insights in the diagnostic potential of sex hormone-binding globulin (SHBG)—clinical approach. Biomedicines. 2025;13(5):1207. 10.3390/biomedicines13051207.
    doi: 10.3390/biomedicines13051207pmc: PMC12109167pubmed: 40427034google scholar: lookup
  31. Osmancevic A, Daka B, Michos ED, Trimpou P, Allison M. The association between inflammation, testosterone and SHBG in men: a cross-sectional multi-ethnic study of atherosclerosis. Clin Endocrinol. 2023;99(2):190–7. 10.1111/cen.14930.
    doi: 10.1111/cen.14930pmc: PMC10330714pubmed: 37221937google scholar: lookup
  32. Saez-Lopez C, Villena JA, Simó R, Selva DM. Sex hormone-binding globulin overexpression protects against high-fat diet-induced obesity in transgenic male mice. J Nutr Biochem. 2020;85:108480. 10.1016/j.jnutbio.2020.108480.
    doi: 10.1016/j.jnutbio.2020.108480pubmed: 32795655google scholar: lookup
  33. Ding EL, Song Y, Manson JE, et al. Sex hormone-binding globulin and risk of type 2 diabetes in women and men. N Engl J Med. 2009;361(12):1152–63. 10.1056/NEJMoa0804381.
    doi: 10.1056/NEJMoa0804381pmc: PMC2774225pubmed: 19657112google scholar: lookup
  34. Bourebaba N, Sikora M, Qasem B, Bourebaba L, Marycz K. Sex hormone-binding globulin (SHBG) mitigates ER stress and improves viability and insulin sensitivity in adipose-derived mesenchymal stem cells (ASC) of equine metabolic syndrome (EMS)-affected horses. Cell Commun Signal. 2023;21(1):230. 10.1186/s12964-023-01254-6.
    doi: 10.1186/s12964-023-01254-6pmc: PMC10496240pubmed: 37697311google scholar: lookup
  35. Henneke DR, Potter GD, Kreider JL, Yeates BF. Relationship between condition score, physical measurements and body fat percentage in mares. Equine Vet J. 1983;15(4):371–2. 10.1111/j.2042-3306.1983.tb01826.x.
    doi: 10.1111/j.2042-3306.1983.tb01826.xpubmed: 6641685google scholar: lookup
  36. Marycz K, Michalak I, Kocherova I, Marędziak M, Weiss C. The enriched by biosorption process in Cr(III) improves viability, and reduces oxidative stress and apoptosis in Equine Metabolic Syndrome derived adipose mesenchymal stromal stem cells (ASCs) and their extracellular vesicles (MV’s). Mar Drugs. 2017;15(12):385. 10.3390/md15120385.n
    doi: 10.3390/md15120385pmc: PMC5742845pubmed: 29292726google scholar: lookup
  37. Bourebaba L, Michalak I, Baouche M, Kucharczyk K, Marycz K. methanolic extract promotes chondrogenic gene expression and cartilage phenotype differentiation in equine adipose-derived mesenchymal stromal stem cells affected by metabolic syndrome. Stem Cell Res Ther. 2019;10(1):392. 10.1186/s13287-019-1499-z.n
    doi: 10.1186/s13287-019-1499-zpmc: PMC6916455pubmed: 31847882google scholar: lookup
  38. Bourebaba N, Kornicka-Garbowska K, Marycz K, Bourebaba L, Kowalczuk A. ethanolic extract attenuates hyperglycemia and hyperinsulinemia-induced insulin resistance in HepG2 cell line through the reduction of oxidative stress and improvement of mitochondrial biogenesis – possible implication in pharmacotherapy. Mitochondrion. 2021;59:190–213. 10.1016/j.mito.2021.06.003.n
    doi: 10.1016/j.mito.2021.06.003pubmed: 34091077google scholar: lookup
  39. Bourebaba L, Komakula SSB, Weiss C, Adrar N, Marycz K. The PTP1B selective inhibitor MSI-1436 mitigates Tunicamycin-induced ER stress in human hepatocarcinoma cell line through XBP1 splicing modulation. PLoS One. 2023;18(1):e0278566. 10.1371/journal.pone.0278566.
    doi: 10.1371/journal.pone.0278566pmc: PMC9844924pubmed: 36649358google scholar: lookup
  40. Kornicka-Garbowska K, Groborz S, Lynda B, Galuppo L, Marycz K. Mitochondria transfer restores fibroblasts-like synoviocytes (FLS) plasticity in LPS-induced, in vitro synovitis model. Cell Commun Signal. 2022;20(1):137. 10.1186/s12964-022-00923-2.
    doi: 10.1186/s12964-022-00923-2pmc: PMC9450291pubmed: 36071528google scholar: lookup
  41. Bourebaba L, Kępska M, Qasem B, et al. Sex hormone-binding globulin improves lipid metabolism and reduces inflammation in subcutaneous adipose tissue of metabolic syndrome-affected horses. Front Mol Biosci. 2023;10:1214961. 10.3389/fmolb.2023.1214961.
    doi: 10.3389/fmolb.2023.1214961pmc: PMC10749534pubmed: 38146533google scholar: lookup
  42. Irwin-Huston JM, Bourebaba L, Bourebaba N, Tomal A, Marycz K. Sex hormone-binding globulin promotes the osteogenic differentiation potential of equine adipose-derived stromal cells by activating the BMP signaling pathway. Front Endocrinol. 2024;15:1424873. 10.3389/fendo.2024.1424873.
    doi: 10.3389/fendo.2024.1424873pmc: PMC11524885pubmed: 39483986google scholar: lookup
  43. Marycz K, Wiatrak B, Irwin-Houston JM, Marcinkowska K, Mularczyk M, Bourebaba L. Sex hormone binding globulin (SHBG) modulates mitochondrial dynamics in PPARγ-depleted equine adipose derived stromal cells. J Mol Med. 2024;102(8):1015–36. 10.1007/s00109-024-02459-z.
    doi: 10.1007/s00109-024-02459-zpmc: PMC11269461pubmed: 38874666google scholar: lookup
  44. Mularczyk M, Bourebaba N, Marycz K, Bourebaba L. Astaxanthin carotenoid modulates oxidative stress in adipose-derived stromal cells isolated from equine metabolic syndrome affected horses by targeting mitochondrial biogenesis. Biomolecules. 2022;12(8):1039. 10.3390/biom12081039.
    doi: 10.3390/biom12081039pmc: PMC9405637pubmed: 36008933google scholar: lookup
  45. Alicka M, Kornicka-Garbowska K, Kucharczyk K, Kępska M, Rӧcken M, Marycz K. Age-dependent impairment of adipose-derived stem cells isolated from horses. Stem Cell Res Ther. 2020;11(1):4. 10.1186/s13287-019-1512-6.
    doi: 10.1186/s13287-019-1512-6pmc: PMC6942290pubmed: 31900232google scholar: lookup
  46. Marycz K, Kornicka K, Grzesiak J, Śmieszek A, Szłapka J. Macroautophagy and selective mitophagy ameliorate chondrogenic differentiation potential in adipose stem cells of equine metabolic syndrome: new findings in the field of progenitor cells differentiation. Oxid Med Cell Longev. 2016;2016:1–18. 10.1155/2016/3718468.
    doi: 10.1155/2016/3718468pmc: PMC5178365pubmed: 28053691google scholar: lookup
  47. Reynolds A, Keen JA, Fordham T, Morgan RA. Adipose tissue dysfunction in obese horses with equine metabolic syndrome. Equine Vet J. 2019;51(6):760–6. 10.1111/evj.13097.
    doi: 10.1111/evj.13097pmc: PMC6850304pubmed: 30866087google scholar: lookup
  48. Marycz K, Weiss C. Evaluation of oxidative stress and mitophagy during adipogenic differentiation of adipose-derived stem cells isolated from Equine Metabolic Syndrome (EMS) Horses. Stem Cells International. 2018;2018:1–18. 10.1155/2018/5340756.
    pmc: PMC6011082pubmed: 29977307
  49. Parra-Peralbo E, Talamillo A, Barrio R. Origin and development of the adipose tissue, a key organ in physiology and disease. Front Cell Dev Biol. 2021;9:786129. 10.3389/fcell.2021.786129.
    doi: 10.3389/fcell.2021.786129pmc: PMC8724577pubmed: 34993199google scholar: lookup
  50. Miana VV, Prieto González EA. Adipose tissue stem cells in regenerative medicine. Ecancermedicalscience. 2018;12. 10.3332/ecancer.2018.822.
    doi: 10.3332/ecancer.2018.822pmc: PMC5880231pubmed: 29662535google scholar: lookup
  51. Rohban R, Pieber TR. Mesenchymal stem and progenitor cells in regeneration: tissue specificity and regenerative potential. Stem Cells Int. 2017;2017:1–16. 10.1155/2017/5173732.
    doi: 10.1155/2017/5173732pmc: PMC5327785pubmed: 28286525google scholar: lookup
  52. Nellinger S, Kluger PJ. How mechanical and physicochemical material characteristics influence adipose-derived stem cell fate. IJMS. 2023;24(4):3551. 10.3390/ijms24043551.
    doi: 10.3390/ijms24043551pmc: PMC9961531pubmed: 36834966google scholar: lookup
  53. Seo Y, Shin TH, Kim HS. Current strategies to enhance adipose stem cell function: an update. IJMS. 2019;20(15):3827. 10.3390/ijms20153827.
    doi: 10.3390/ijms20153827pmc: PMC6696067pubmed: 31387282google scholar: lookup
  54. Kumar P, Nagarajan A, Uchil PD. Analysis of cell viability by the lactate dehydrogenase assay. Cold Spring Harb Protoc. 2018;2018(6):pdb.prot095497. 10.1101/pdb.prot095497.
    doi: 10.1101/pdb.prot095497pubmed: 29858337google scholar: lookup
  55. Farhana A, Lappin SL. Biochemistry, lactate dehydrogenase. InStatPearls. StatPearls Publishing; 2025. Accessed 19Aug 2025. http://www.ncbi.nlm.nih.gov/books/NBK557536/.
    pubmed: 32491468
  56. Dharmalingam M, Yamasandhi Pg. Nonalcoholic fatty liver disease and type 2 diabetes mellitus. Indian J Endocr Metab. 2018;22(3):421. 10.4103/ijem.IJEM_585_17.
    doi: 10.4103/ijem.IJEM_585_17pmc: PMC6063173pubmed: 30090738google scholar: lookup
  57. Zorov DB, Juhaszova M, Sollott SJ. Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiol Rev. 2014;94(3):909–50. 10.1152/physrev.00026.2013.
    doi: 10.1152/physrev.00026.2013pmc: PMC4101632pubmed: 24987008google scholar: lookup
  58. Frohnert BI, Bernlohr DA. Protein carbonylation, mitochondrial dysfunction, and insulin resistance. Adv Nutr. 2013;4(2):157–63. 10.3945/an.112.003319.
    doi: 10.3945/an.112.003319pmc: PMC3649096pubmed: 23493532google scholar: lookup
  59. Titone R, Robertson DM. Insulin receptor preserves mitochondrial function by binding VDAC1 in insulin insensitive mucosal epithelial cells. FASEB J. 2020;34(1):754–75. 10.1096/fj.201901316RR.
    doi: 10.1096/fj.201901316RRpmc: PMC7346881pubmed: 31914671google scholar: lookup
  60. Deas E, Wood NW, Plun-Favreau H. Mitophagy and Parkinson’s disease: the PINK1–parkin link. Biochim Biophys Acta. 2011;1813(4):623–33. 10.1016/j.bbamcr.2010.08.007.
    doi: 10.1016/j.bbamcr.2010.08.007pmc: PMC3925795pubmed: 20736035google scholar: lookup
  61. Ngo DTM, Sverdlov AL, Karki S, et al. Oxidative modifications of mitochondrial complex II are associated with insulin resistance of visceral fat in obesity. Am J Physiol Endocrinol Metab. 2019;316(2):E168–77. 10.1152/ajpendo.00227.2018.
    doi: 10.1152/ajpendo.00227.2018pmc: PMC6397365pubmed: 30576243google scholar: lookup
  62. Marycz K, Kornicka K, Grzesiak J, Śmieszek A, Szłapka J. Macroautophagy and selective mitophagy ameliorate chondrogenic differentiation potential in adipose stem cells of equine metabolic syndrome: new findings in the field of progenitor cells differentiation. Oxid Med Cell Longev. 2016;2016(1):3718468. 10.1155/2016/3718468. Liton PB, ed.
    doi: 10.1155/2016/3718468pmc: PMC5178365pubmed: 28053691google scholar: lookup
  63. Stefaniuk-Szmukier M, Piórkowska K, Ropka-Molik K. Equine metabolic syndrome: a complex disease influenced by multifactorial genetic factors. Genes. 2023;14(8):1544. 10.3390/genes14081544.
    doi: 10.3390/genes14081544pmc: PMC10454496pubmed: 37628596google scholar: lookup
  64. Suagee JK, Corl BA, Geor RJ. A potential role for pro-inflammatory cytokines in the development of insulin resistance in horses. Animals. 2012;2(2):243–60. 10.3390/ani2020243.
    doi: 10.3390/ani2020243pmc: PMC4494330pubmed: 26486919google scholar: lookup
  65. Gavrilin MA, McAndrew CC, Prather ER, et al. Inflammasome adaptor ASC is highly elevated in lung over plasma and relates to inflammation and lung diffusion in the absence of speck formation. Front Immunol. 2020;11:461. 10.3389/fimmu.2020.00461.
    doi: 10.3389/fimmu.2020.00461pmc: PMC7096349pubmed: 32265920google scholar: lookup
  66. Kornicka K, Śmieszek A, Węgrzyn A, Röcken M, Marycz K. Immunomodulatory properties of adipose-derived stem cells treated with 5-azacytydine and resveratrol on peripheral blood mononuclear cells and macrophages in metabolic syndrome animals. JCM. 2018;7(11):383. 10.3390/jcm7110383.
    doi: 10.3390/jcm7110383pmc: PMC6262510pubmed: 30356025google scholar: lookup
  67. Tian R, Zhu Y, Yao J, et al. Nlrp3 participates in the regulation of EMT in bleomycin-induced pulmonary fibrosis. Exp Cell Res. 2017;357(2):328–34. 10.1016/j.yexcr.2017.05.028.
    doi: 10.1016/j.yexcr.2017.05.028pubmed: 28591554google scholar: lookup
  68. Shoelson SE. Inflammation and insulin resistance. J Clin Invest. 2006;116(7):1793–801. 10.1172/JCI29069.
    doi: 10.1172/JCI29069pmc: PMC1483173pubmed: 16823477google scholar: lookup
  69. Tsalamandris S, Antonopoulos AS, Oikonomou E, et al. The role of inflammation in diabetes: current concepts and future perspectives. Eur Cardiol. 2019;14(1):50–9. 10.15420/ecr.2018.33.1.
    doi: 10.15420/ecr.2018.33.1pmc: PMC6523054pubmed: 31131037google scholar: lookup
  70. Rohm TV, Meier DT, Olefsky JM, Donath MY. Inflammation in obesity, diabetes, and related disorders. Immunity. 2022;55(1):31–55. 10.1016/j.immuni.2021.12.013.
    doi: 10.1016/j.immuni.2021.12.013pmc: PMC8773457pubmed: 35021057google scholar: lookup
  71. Ksontini R. Revisiting the role of tumor necrosis factor α and the response to surgical injury and inflammation. Arch Surg. 1998;133(5):558. 10.1001/archsurg.133.5.558.
    doi: 10.1001/archsurg.133.5.558pubmed: 9605921google scholar: lookup
  72. Platzer C, Meisel Ch, Vogt K, Platzer M, Volk HD. Up-regulation of monocytic IL-10 by tumor necrosis factor-α and cAMP elevating drugs. Int Immunol. 1995;7(4):517–23. 10.1093/intimm/7.4.517.
    doi: 10.1093/intimm/7.4.517pubmed: 7547677google scholar: lookup
  73. Van Der Poll T, Jansen J, Levi M, Ten Cate H, Ten Cate JW, Van Deventer SJ. Regulation of interleukin 10 release by tumor necrosis factor in humans and chimpanzees. J Exp Med. 1994;180(5):1985–8. 10.1084/jem.180.5.1985.
    doi: 10.1084/jem.180.5.1985pmc: PMC2191735pubmed: 7964475google scholar: lookup
  74. Liu H, Sidiropoulos P, Song G, et al. TNF-α gene expression in macrophages: regulation by NF-κB is independent of c-Jun or C/EBPβ. J Immunol. 2000;164(8):4277–85. 10.4049/jimmunol.164.8.4277.
    doi: 10.4049/jimmunol.164.8.4277pubmed: 10754326google scholar: lookup

Citations

This article has been cited 0 times.
Subscribe to our newsletter
Join 99,001 horse owners like you who receive our email updates on horse health and nutrition.