FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / Animals (Basel) / Obesity-Associated Metabolomic and Functional Reprogramming ...
Animals : an open access journal from MDPI2025; 15(13); 1992; doi: 10.3390/ani15131992

Obesity-Associated Metabolomic and Functional Reprogramming in Neutrophils from Horses with Asthma.

Abstract: Equine asthma is a chronic respiratory disease characterised by neutrophilic inflammation, airway hyperresponsiveness, and impaired pulmonary function. Obesity, increasingly prevalent among domestic horses, has been identified as a potential risk factor for exacerbating inflammatory conditions. This study aimed to explore whether obesity modifies neutrophil metabolism and inflammatory responses in horses affected by asthma. Six asthmatic horses in clinical remission were categorised into two groups: obese and non-obese, based on body condition score. Serum levels of interleukin-1β (IL-1β) and peripheral blood neutrophil counts were significantly higher in obese horses, indicating a heightened systemic inflammatory state. Neutrophils from obese horses displayed a stronger oxidative burst following zymosan stimulation and elevated IL-1β gene expression in response to lipopolysaccharide, suggesting a hyperinflammatory phenotype. Metabolomic profiling of neutrophils identified 139 metabolites, with notable differences in fatty acids, branched-chain amino acids, and tricarboxylic acid (TCA) cycle intermediates. Pathway enrichment analysis revealed significant alterations in fatty acid biosynthesis, amino acid metabolism, and glutathione-related pathways. Elevated levels of itaconate, citraconic acid, and citrate in obese horses indicate profound metabolic reprogramming within neutrophils. These results suggest that obesity promotes a distinct neutrophil phenotype marked by increased metabolic activity and heightened responsiveness to inflammatory stimuli. This altered profile may contribute to the persistence or worsening of airway inflammation in asthmatic horses. The findings underscore the importance of addressing obesity in the clinical management of equine asthma and open avenues for further research into metabolic-targeted therapies in veterinary medicine.
Get Full Text
Publication Date: 2025-07-07 PubMed ID: 40646891PubMed Central: PMC12248518DOI: 10.3390/ani15131992Google 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.

This study investigates how obesity, a common issue in domestic horses, affects the inflammation responses in horses suffering from asthma, a chronic respiratory disease. The findings suggest that obesity can enhance the metabolic activity and inflammatory responsiveness of neutrophils, potentially exacerbating asthma symptoms.

Understanding the Research

The researchers aimed to understand the relationship between obesity and inflammation in asthmatic horses by analyzing neutrophil metabolism and inflammatory responses in these animals. Neutrophils, a type of white blood cell, play crucial roles in inflammation and immune response.

  • Two groups of asthmatic horses, categorized as obese and non-obese using Body Condition Score, were used in the study.
  • Higher levels of interleukin-1β (a pro-inflammatory molecule) and increased neutrophil counts were found in the blood of obese horses. This indicated a stronger systemic inflammatory state in obese horses.
  • Upon stimulation with zymosan (a substance derived from yeast cell walls), neutrophils from obese horses generated a stronger oxidative burst, indicating a heightened inflammatory response.
  • Neutrophils from obese horses, when exposed to lipopolysaccharide (a potent inflammation trigger), showed higher expression of IL-1β gene, suggesting an enhanced pro-inflammatory phenotype.

Metabolomic Profiling

Metabolomic profiling of neutrophils from obese and non-obese horses was performed to look for differences in metabolite concentration which may be associated with obesity.

  • The profile revealed 139 different metabolites, with significant differences observed in fatty acids, branched-chain amino acids, and tricarboxylic acid (TCA) cycle intermediates between the two groups.
  • Alterations in fatty acid biosynthesis, amino acid metabolism, and glutathione-related pathways were identified, possibly due to obesity.
  • The significantly higher levels of itaconate, citraconic acid, and citrate in obese horses indicate major metabolic reprogramming within the neutrophils.

Conclusions and Implications

The findings suggest that obesity can induce a distinct neutrophil phenotype characterized by increased metabolic activity and an enhanced response to inflammatory stimuli.

  • This altered profile may induce or worsen airway inflammation in asthmatic horses, which emphasizes the importance of managing obesity in these animals.
  • The study also opens up possibilities for more research into therapies targeted at metabolic pathways in veterinary medicine.

The study has added significant value to the understanding of how obesity can exacerbate inflammatory responses, an aspect that may have wider implications across human and veterinary medicine.

Cite This Article

APA
Albornoz A, Morales B, Fernandez VB, Henriquez C, Quiroga J, Alarcón P, Moran G, Burgos RA. (2025). Obesity-Associated Metabolomic and Functional Reprogramming in Neutrophils from Horses with Asthma. Animals (Basel), 15(13), 1992. https://doi.org/10.3390/ani15131992

Publication

Animals : an open access journal from MDPI
ISSN: 2076-2615
NlmUniqueID: 101635614
Country: Switzerland
Language: English
Volume: 15
Issue: 13
PII: 1992

Researcher Affiliations

Albornoz, Alejandro
  • Institute of Pharmacology and Morphophysiology, Faculty of Veterinary Sciences, Universidad Austral de Chile, Valdivia 5090000, Chile.
Morales, Beatriz
  • Institute of Pharmacology and Morphophysiology, Faculty of Veterinary Sciences, Universidad Austral de Chile, Valdivia 5090000, Chile.
Fernandez, Valentina Bernal
  • Graduate School, Faculty of Veterinary Sciences, Universidad Austral de Chile, Valdivia 5090000, Chile.
Henriquez, Claudio
  • Institute of Pharmacology and Morphophysiology, Faculty of Veterinary Sciences, Universidad Austral de Chile, Valdivia 5090000, Chile.
Quiroga, John
  • Institute of Pharmacology and Morphophysiology, Faculty of Veterinary Sciences, Universidad Austral de Chile, Valdivia 5090000, Chile.
Alarcón, Pablo
  • Institute of Pharmacology and Morphophysiology, Faculty of Veterinary Sciences, Universidad Austral de Chile, Valdivia 5090000, Chile.
Moran, Gabriel
  • Institute of Pharmacology and Morphophysiology, Faculty of Veterinary Sciences, Universidad Austral de Chile, Valdivia 5090000, Chile.
Burgos, Rafael A
  • Institute of Pharmacology and Morphophysiology, Faculty of Veterinary Sciences, Universidad Austral de Chile, Valdivia 5090000, Chile.

Grant Funding

  • 1230101 / Fondo Nacional de Desarrollo Cientu00edfico y Tecnolu00f3gico

Conflict of Interest Statement

All authors declare that they have no conflicts of interest.

References

This article includes 96 references
  1. Couetil L, Cardwell JM, Leguillette R, Mazan M, Richard E, Bienzle D, Bullone M, Gerber V, Ivester K, Lavoie JP. Equine Asthma: Current Understanding and Future Directions. Front. Vet. Sci. 2020;7:450.
    doi: 10.3389/fvets.2020.00450pmc: PMC7438831pubmed: 32903600google scholar: lookup
  2. Bullone M, Lavoie JP. Asthma “of Horses and Men”—How Can Equine Heaves Help Us Better Understand Human Asthma Immunopathology and Its Functional Consequences?. Mol. Immunol. 2015;66:97–105.
    doi: 10.1016/j.molimm.2014.12.005pubmed: 25547716google scholar: lookup
  3. Pirie RS, Couëtil LL, Robinson NE, Lavoie JP. Equine Asthma: An Appropriate, Translational and Comprehendible Terminology?. Equine Vet. J. 2016;48:403–405.
    doi: 10.1111/evj.12586pubmed: 27292020google scholar: lookup
  4. Davis KU, Sheats MK. The Role of Neutrophils in the Pathophysiology of Asthma in Humans and Horses. Inflammation 2021;44:450–465.
    doi: 10.1007/s10753-020-01362-2pubmed: 33150539google scholar: lookup
  5. Robinson NE. International Workshop on Equine Chronic Airway Disease. Michigan State University 16–18 June 2000. Equine Vet. J. 2001;33:5–19.
    doi: 10.2746/042516401776767412pubmed: 11191611google scholar: lookup
  6. Uberti B, Morán G. Role of Neutrophils in Equine Asthma. Anim. Health Res. Rev. 2018;19:65–73.
    doi: 10.1017/S146625231800004Xpubmed: 29792391google scholar: lookup
  7. Smith U, Kahn BB. Adipose Tissue Regulates Insulin Sensitivity: Role of Adipogenesis, de Novo Lipogenesis and Novel Lipids. J. Intern. Med. 2016;280:465–475.
    doi: 10.1111/joim.12540pmc: PMC5218584pubmed: 27699898google scholar: lookup
  8. Gomez-Llorente MA, Romero R, Chueca N, Martinez-Cañavate A, Gomez-Llorente C. Obesity and Asthma: A Missing Link. Int. J. Mol. Sci. 2017;18:1490.
    doi: 10.3390/ijms18071490pmc: PMC5535980pubmed: 28696379google scholar: lookup
  9. Sandøe P, Palmer C, Corr S, Astrup A, Bjørnvad CR. Canine and Feline Obesity: A One Health Perspective. Vet. Rec. 2014;175:610–616.
    doi: 10.1136/vr.g7521pubmed: 25523996google scholar: lookup
  10. Kosolofski HR, Gow SP, Robinson KA. Prevalence of Obesity in the Equine Population of Saskatoon and Surrounding Area. Can. Vet. J. 2017;58:967–970.
    pmc: PMC5556474pubmed: 28878421
  11. Wyse CA, McNie KA, Tannahil VJ, Murray JK, Love S. Prevalence of Obesity in Riding Horses in Scotland. Vet. Rec. 2008;162:590–591.
    doi: 10.1136/vr.162.18.590pubmed: 18453379google scholar: lookup
  12. Thatcher CD, Pleasant RS, Geor RJ, Elvinger F. Prevalence of Overconditioning in Mature Horses in Southwest Virginia during the Summer. J. Vet. Intern. Med. 2012;26:1413–1418.
    doi: 10.1111/j.1939-1676.2012.00995.xpubmed: 22946995google scholar: lookup
  13. Jaqueth AL, Iwaniuk ME, Burk AO. Characterization of the Prevalence and Management of Over-Conditioned Ponies and Horses in Maryland. J. Equine Vet. Sci. 2018;68:26–32.
    doi: 10.1016/j.jevs.2018.02.007pubmed: 31256884google scholar: lookup
  14. Durham AE. Endocrine Disease in Aged Horses. Vet. Clin. N. Am.-Equine Pract. 2016;32:301–315.
    doi: 10.1016/j.cveq.2016.04.007pubmed: 27449391google scholar: lookup
  15. Stephenson HM, Green MJ, Freeman SL. Short Communications: Prevalence of Obesity in a Population of Horses in the UK. Vet. Rec. 2011;168:131.
    doi: 10.1136/vr.c6281pubmed: 21257596google scholar: lookup
  16. Bantulà M, Roca-Ferrer J, Arismendi E, Picado C. Asthma and Obesity: Two Diseases on the Rise and Bridged by Inflammation. J. Clin. Med. 2021;10:169.
    doi: 10.3390/jcm10020169pmc: PMC7825135pubmed: 33418879google scholar: lookup
  17. Camargo CA, Weiss ST, Zhang S, Willett WC, Speizer FE. Prospective Study of Body Mass Index, Weight Change, and Risk of Adult- Onset Asthma in Women. Arch. Intern. Med. 1999;159:2582–2588.
    doi: 10.1001/archinte.159.21.2582pubmed: 10573048google scholar: lookup
  18. Shaheen SO, Sterne JAC, Montgomery SM, Azima H. Birth Weight, Body Mass Index and Asthma in Young Adults. Thorax 1999;54:396–402.
    doi: 10.1136/thx.54.5.396pmc: PMC1763790pubmed: 10212102google scholar: lookup
  19. Beckett WS, Jacobs DR, Xinhua YU, Iribarren C, Dale Williams O. Asthma Is Associated with Weight Gain in Females but Not Males, Independent of Physical Activity. Am. J. Respir. Crit. Care Med. 2001;164:2045–2050.
    doi: 10.1164/ajrccm.164.11.2004235pubmed: 11739133google scholar: lookup
  20. Chen Y, Dales R, Tang M, Krewski D. Obesity May Increase the Incidence of Asthma in Women but Not in Men: Longitudinal Observations from the Canadian National Population Health Surveys. Am. J. Epidemiol. 2002;155:191–197.
    doi: 10.1093/aje/155.3.191pubmed: 11821241google scholar: lookup
  21. Xu B, Pekkanen J, Laitinen J, Järvelin MR. Body Build from Birth to Adulthood and Risk of Asthma. Eur. J. Public Health. 2002;12:166–170.
    doi: 10.1093/eurpub/12.3.166pubmed: 12232953google scholar: lookup
  22. Guerra S, Sherrill DL, Bobadilla A, Martinez FD, Barbee RA. The Relation of Body Mass Index to Asthma, Chronic Bronchitis, and Emphysema. Chest 2002;122:1256–1263.
    doi: 10.1378/chest.122.4.1256pubmed: 12377850google scholar: lookup
  23. Huovinen E, Kaprio J, Koskenvuo M. Factors Associated to Lifestyle and Risk of Adult Onset Asthma. Respir. Med. 2003;97:273–280.
    doi: 10.1053/rmed.2003.1419pubmed: 12645835google scholar: lookup
  24. Nystad W, Meyer HE, Nafstad P, Tverdal A, Engeland A. Body Mass Index in Relation to Adult Asthma among 135,000 Norwegian Men and Women. Am. J. Epidemiol. 2004;160:969–976.
    doi: 10.1093/aje/kwh303pubmed: 15522853google scholar: lookup
  25. Ford ES. The Epidemiology of Obesity and Asthma. J. Allergy Clin. Immunol. 2005;115:897–909.
    doi: 10.1016/j.jaci.2004.11.050pubmed: 15867841google scholar: lookup
  26. Kronander UN, Falkenberg M, Olle Z. Prevalence and Incidence of Asthma Related to Waist Circumference and BMI in a Swedish Community Sample. Respir. Med. 2004;98:1108–1116.
    doi: 10.1016/j.rmed.2004.03.022pubmed: 15526812google scholar: lookup
  27. Von Behren J, Lipsett M, Horn-Ross PL, Delfino RJ, Gilliland F, McConnell R, Bernstein L, Clarke CA, Reynolds P. Obesity, Waist Size and Prevalence of Current Asthma in the California Teachers Study Cohort. Thorax 2009;64:889–893.
    doi: 10.1136/thx.2009.114579pmc: PMC2813683pubmed: 19706838google scholar: lookup
  28. Apostolopoulos V, de Courten MPJ, Stojanovska L, Blatch GL, Tangalakis K, de Courten B. The Complex Immunological and Inflammatory Network of Adipose Tissue in Obesity. Mol. Nutr. Food Res. 2016;60:43–57.
    doi: 10.1002/mnfr.201500272pubmed: 26331761google scholar: lookup
  29. Sood A. Obesity, Adipokines, and Lung Disease. J. Appl. Physiol. 2010;108:744–753.
    doi: 10.1152/japplphysiol.00838.2009pmc: PMC2838636pubmed: 19926824google scholar: lookup
  30. Arteaga-Solis E, Zee T, Emala CW, Vinson C, Wess J, Karsenty G. Inhibition of Leptin Regulation of Parasympathetic Signaling as a Cause of Extreme Body Weight-Associated Asthma. Cell Metab. 2013;17:35–48.
    doi: 10.1016/j.cmet.2012.12.004pmc: PMC3815545pubmed: 23312282google scholar: lookup
  31. Tashiro H, Shore SA. Obesity and Severe Asthma. Allergol. Int. 2019;68:135–142.
    doi: 10.1016/j.alit.2018.10.004pmc: PMC6540088pubmed: 30509734google scholar: lookup
  32. Schatz M, Hsu JWY, Zeiger RS, Chen W, Dorenbaum A, Chipps BE, Haselkorn T. Phenotypes Determined by Cluster Analysis in Severe or Difficult-to-Treat Asthma. J. Allergy Clin. Immunol. 2014;133:1549–1556.
    doi: 10.1016/j.jaci.2013.10.006pubmed: 24315502google scholar: lookup
  33. Ather JL, Poynter ME, Dixon AE. Immunological Characteristics and Management Considerations in Obese Patients with Asthma. Expert Rev. Clin. Immunol. 2015;11:793–803.
    doi: 10.1586/1744666X.2015.1040394pmc: PMC4696863pubmed: 25914932google scholar: lookup
  34. Dixon A. The Treatment of Asthma in Obesity. Expert Rev. Respir. Med. 2012;6:331–340.
    doi: 10.1586/ers.12.22pubmed: 22788947google scholar: lookup
  35. Mohan A, Grace J, Wang BR, Lugogo N. The Effects of Obesity in Asthma. Curr. Allergy Asthma Rep. 2019;19:1–10.
    doi: 10.1007/s11882-019-0877-zpubmed: 31506820google scholar: lookup
  36. Thomas SJ, de Solis CN, Coleman MC. Case-Control Study of Risk Factors for Equine Asthma in Texas. J. Equine Vet. Sci. 2021;103:103644.
    doi: 10.1016/j.jevs.2021.103644pubmed: 34281649google scholar: lookup
  37. Hu C, Xuan Y, Zhang X, Liu Y, Yang S, Yang K. Immune Cell Metabolism and Metabolic Reprogramming. Mol. Biol. Rep. 2022;49:9783–9795.
    doi: 10.1007/s11033-022-07474-2pmc: PMC9189272pubmed: 35696048google scholar: lookup
  38. Møller SH, Wang L, Ho PC. Metabolic Programming in Dendritic Cells Tailors Immune Responses and Homeostasis. Cell. Mol. Immunol. 2022;19:370–383.
    doi: 10.1038/s41423-021-00753-1pmc: PMC8891341pubmed: 34413487google scholar: lookup
  39. Wu L, Yan Z, Jiang Y, Chen Y, Du J, Guo L, Xu J, Luo Z, Liu Y. Metabolic Regulation of Dendritic Cell Activation and Immune Function during Inflammation. Front. Immunol. 2023;14:1140749.
    doi: 10.3389/fimmu.2023.1140749pmc: PMC10030510pubmed: 36969180google scholar: lookup
  40. Ettel P, Weichhart T. Not Just Sugar: Metabolic Control of Neutrophil Development and Effector Functions. J. Leukoc. Biol. 2024;116:487–510.
    doi: 10.1093/jleuko/qiae057pmc: PMC7617515pubmed: 38450755google scholar: lookup
  41. Rogers T, DeBerardinis RJ. Metabolic Plasticity of Neutrophils: Relevance to Pathogen Responses and Cancer. Trends Cancer. 2021;7:700–713.
    doi: 10.1016/j.trecan.2021.04.007pmc: PMC9270875pubmed: 34023325google scholar: lookup
  42. Yipeng Z, Chao C, Ranran L, Tingting P, Hongping Q. Metabolism: A Potential Regulator of Neutrophil Fate. Front. Immunol. 2024;15:1500676.
    doi: 10.3389/fimmu.2024.1500676pmc: PMC11652355pubmed: 39697327google scholar: lookup
  43. Morrison T, Watts ER, Sadiku P, Walmsley SR. The Emerging Role for Metabolism in Fueling Neutrophilic Inflammation. Immunol. Rev. 2023;314:427–441.
    doi: 10.1111/imr.13157pmc: PMC10953397pubmed: 36326284google scholar: lookup
  44. Pastorek M, Konečná B, Janko J, Janovičová Ľ, Podracká Ľ, Záhumenský J, Šteňová E, Dúbrava M, Hodosy J, Vlková B. Mitochondria-Induced Formation of Neutrophil Extracellular Traps Is Enhanced in the Elderly via Toll-like Receptor 9. J. Leukoc. Biol. 2023;114:651–665.
    doi: 10.1093/jleuko/qiad101pubmed: 37648664google scholar: lookup
  45. Cao Z, Zhao M, Sun H, Hu L, Chen Y, Fan Z. Roles of Mitochondria in Neutrophils. Front. Immunol. 2022;13:934444.
    doi: 10.3389/fimmu.2022.934444pmc: PMC9447286pubmed: 36081497google scholar: lookup
  46. Herring SE, Mao S, Bhalla M, Tchalla EYI, Kramer JM, Bou Ghanem EN. Mitochondrial ROS Production by Neutrophils Is Required for Host Antimicrobial Function against Streptococcus Pneumoniae and Is Controlled by A2B Adenosine Receptor Signaling. PLoS Pathog. 2022;18:e1010700.
    doi: 10.1371/journal.ppat.1010700pmc: PMC9704767pubmed: 36374941google scholar: lookup
  47. Fossati G, Moulding DA, Spiller DG, Moots RJ, White MRH, Edwards SW. The Mitochondrial Network of Human Neutrophils: Role in Chemotaxis, Phagocytosis, Respiratory Burst Activation, and Commitment to Apoptosis. J. Immunol. 2003;170:1964–1972.
    doi: 10.4049/jimmunol.170.4.1964pubmed: 12574365google scholar: lookup
  48. Lavoie JP, Bullone M, Rodrigues N, Germim P, Albrecht B, von Salis-Soglio M. Effect of Different Doses of Inhaled Ciclesonide on Lung Function, Clinical Signs Related to Airflow Limitation and Serum Cortisol Levels in Horses with Experimentally Induced Mild to Severe Airway Obstruction. Equine Vet. J. 2019;51:779–786.
    doi: 10.1111/evj.13093pmc: PMC7379559pubmed: 30854685google scholar: lookup
  49. Henneke DR, Potter GD, Kreider JL, Yeates BF. Relationship between Condition Score, Physical Measurements and Body Fat Percentage in Mares. Equine Vet. J. 1983;15:371–372.
    doi: 10.1111/j.2042-3306.1983.tb01826.xpubmed: 6641685google scholar: lookup
  50. Perez B, Henriquez C, Sarmiento J, Morales N, Folch H, Galesio JS, Uberti B, Morán G. Tamoxifen as a New Therapeutic Tool for Neutrophilic Lung Inflammation. Respirology 2016;21:112–118.
    doi: 10.1111/resp.12664pubmed: 26510482google scholar: lookup
  51. Alarcon P, Hidalgo AI, Manosalva C, Cristi R, Teuber S, Hidalgo MA, Burgos RA. Metabolic Disturbances in Synovial Fluid Are Involved in the Onset of Synovitis in Heifers with Acute Ruminal Acidosis. Sci. Rep. 2019;9:5452.
    doi: 10.1038/s41598-019-42007-1pmc: PMC6443794pubmed: 30932023google scholar: lookup
  52. Albornoz A, Alarcon P, Morales N, Uberti B, Henriquez C, Manosalva C, Burgos RA, Moran G. Metabolomics Analysis of Bronchoalveolar Lavage Fluid Samples in Horses with Naturally-Occurring Asthma and Experimentally-Induced Airway Inflammation. Res. Vet. Sci. 2020;133:276–282.
    doi: 10.1016/j.rvsc.2020.09.033pubmed: 33039879google scholar: lookup
  53. Borlone C, Morales N, Henriquez C, Folch H, Olave C, Sarmiento J, Uberti B, Moran G. In Vitro Effects of Tamoxifen on Equine Neutrophils. Res. Vet. Sci. 2017;110:60–64.
    doi: 10.1016/j.rvsc.2016.11.003pubmed: 28159238google scholar: lookup
  54. Chong J, Soufan O, Li C, Caraus I, Li S, Bourque G, Wishart DS, Xia J. MetaboAnalyst 4.0: Towards More Transparent and Integrative Metabolomics Analysis. Nucleic Acids Res. 2018;46:W486–W494.
    doi: 10.1093/nar/gky310pmc: PMC6030889pubmed: 29762782google scholar: lookup
  55. Caër C, Rouault C, Le Roy T, Poitou C, Aron-Wisnewsky J, Torcivia A, Bichet JC, Clément K, Guerre-Millo M, André S. Immune Cell-Derived Cytokines Contribute to Obesity-Related Inflammation, Fibrogenesis and Metabolic Deregulation in Human Adipose Tissue. Sci. Rep. 2017;7:3000.
    doi: 10.1038/s41598-017-02660-wpmc: PMC5462798pubmed: 28592801google scholar: lookup
  56. Carobbio S, Pellegrinelli V, Vidal-Puig A. Adipose Tissue Function and Expandability as Determinants of Lipotoxicity and the Metabolic Syndrome. Adv. Exp. Med. Biol. 2017;960:161–196.
    pubmed: 28585199
  57. Bing C. Is Interleukin-1 b a Culprit in Macrophage-Adipocyte Crosstalk in Obesity?. Adipocyte 2015;4:149–152.
    doi: 10.4161/21623945.2014.979661pmc: PMC4496963pubmed: 26167419google scholar: lookup
  58. Hildebrandt X, Ibrahim M, Peltzer N. Cell Death and Inflammation during Obesity: “Know My Methods, WAT(Son)”. Cell Death Differ. 2023;30:279–292.
    doi: 10.1038/s41418-022-01062-4pmc: PMC9520110pubmed: 36175539google scholar: lookup
  59. Sauter NS, Schulthess FT, Galasso R, Castellani LW, Maedler K. The Antiinflammatory Cytokine Interleukin-1 Receptor Antagonist Protects from High-Fat Diet-Induced Hyperglycemia. Endocrinology 2008;149:2208–2218.
    doi: 10.1210/en.2007-1059pmc: PMC2734491pubmed: 18239070google scholar: lookup
  60. Rhee H, Love T, Harrington D. Blood Neutrophil Count Is Associated with Body Mass Index in Adolescents with Asthma. JSM Allergy Asthma 2018;3:1019.
    pmc: PMC6287916pubmed: 30542672
  61. Gállego-Suárez C, Bulan A, Hirschfeld E, Wachowiak P, Abrishami S, Griffin C, Sturza J, Tzau A, Hayes T, Woolford SJ. Enhanced Myeloid Leukocytes in Obese Children and Adolescents at Risk for Metabolic Impairment. Front. Endocrinol. 2020;11:327.
    doi: 10.3389/fendo.2020.00327pmc: PMC7266967pubmed: 32528415google scholar: lookup
  62. Thind MK, Uhlig HH, Glogauer M, Palaniyar N, Bourdon C, Gwela A, Lancioni CL, Berkley JA, Bandsma RHJ, Farooqui A. A Metabolic Perspective of the Neutrophil Life Cycle: New Avenues in Immunometabolism. Front. Immunol. 2023;14:1334205.
    doi: 10.3389/fimmu.2023.1334205pmc: PMC10800387pubmed: 38259490google scholar: lookup
  63. Lanza IR, Zhang S, Ward LE, Karakelides H, Raftery D, Sreekumaran Nair K. Quantitative Metabolomics by 1H-NMR and LC-MS/MS Confirms Altered Metabolic Pathways in Diabetes. PLoS ONE 2010;5:e10538.
    doi: 10.1371/journal.pone.0010538pmc: PMC2866659pubmed: 20479934google scholar: lookup
  64. Suhre K, Meisinger C, Döring A, Altmaier E, Belcredi P, Gieger C, Chang D, Milburn MV, Gall WE, Weinberger KM. Metabolic Footprint of Diabetes: A Multiplatform Metabolomics Study in an Epidemiological Setting. PLoS ONE 2010;5:e13953.
    doi: 10.1371/journal.pone.0013953pmc: PMC2978704pubmed: 21085649google scholar: lookup
  65. Wang TJ, Larson MG, Vasan RS, Cheng S, Rhee EP, McCabe E, Lewis GD, Fox CS, Jacques PF, Fernandez C. Metabolite Profiles and the Risk of Developing Diabetes. Nat. Med. 2011;17:448–453.
    doi: 10.1038/nm.2307pmc: PMC3126616pubmed: 21423183google scholar: lookup
  66. Friedrich N. Metabolomics in Diabetes Research. J. Endocrinol. 2012;215:29–42.
    doi: 10.1530/JOE-12-0120pubmed: 22718433google scholar: lookup
  67. Newgard CB, An J, Bain JR, Muehlbauer MJ, Stevens RD, Lien LF, Haqq AM, Shah SH, Arlotto M, Slentz CA. A Branched-Chain Amino Acid-Related Metabolic Signature That Differentiates Obese and Lean Humans and Contributes to Insulin Resistance. Cell Metab. 2009;9:311–326.
    doi: 10.1016/j.cmet.2009.02.002pmc: PMC3640280pubmed: 19356713google scholar: lookup
  68. Newgard CB. Interplay between Lipids and Branched-Chain Amino Acids in Development of Insulin Resistance. Cell Metab. 2012;15:606–614.
    doi: 10.1016/j.cmet.2012.01.024pmc: PMC3695706pubmed: 22560213google scholar: lookup
  69. Huffman KM, Shah SH, Stevens RD, Bain JR, Muehlbauer M, Slentz CA, Tanner CJ, Kuchibhatla M, Houmard JA, Newgard CB. Relationships between Circulating Metabolic Intermediates and Insulin Action in Overweight to Obese, Inactive Men and Women. Diabetes Care 2009;32:1678–1683.
    doi: 10.2337/dc08-2075pmc: PMC2732163pubmed: 19502541google scholar: lookup
  70. Perng W, Gillman MW, Fleisch AF, Michalek RD, Watkins SM, Isganaitis E, Patti ME, Oken E. Metabolomic Profiles and Childhood Obesity. Obesity 2014;22:2570–2578.
    doi: 10.1002/oby.20901pmc: PMC4236243pubmed: 25251340google scholar: lookup
  71. Palmer ND, Stevens RD, Antinozzi PA, Anderson A, Bergman RN, Wagenknecht LE, Newgard CB, Bowden DW. Metabolomic Profile Associated with Insulin Resistance and Conversion to Diabetes in the Insulin Resistance Atherosclerosis Study. J. Clin. Endocrinol. Metab. 2015;100:E463–E468.
    doi: 10.1210/jc.2014-2357pmc: PMC4333040pubmed: 25423564google scholar: lookup
  72. Walford GA, Ma Y, Clish C, Florez JC, Wang TJ, Gerszten RE. Metabolite Profiles of Diabetes Incidence and Intervention Response in the Diabetes Prevention Program. Diabetes 2016;65:1424–1433.
    doi: 10.2337/db15-1063pmc: PMC4839205pubmed: 26861782google scholar: lookup
  73. Wurtz P, Soininen P, Kangas AJ, Rönnemaa T, Lehtimäki T, Kähönen M, Viikari JS, Raitakari OT, Ala-Korpela M. Branched-Chain and Aromatic Amino Acidsare Predictors of Insulinresistance in Young Adults. Diabetes Care 2013;36:648–655.
    doi: 10.2337/dc12-0895pmc: PMC3579331pubmed: 23129134google scholar: lookup
  74. Vanweert F, Schrauwen P, Phielix E. Role of Branched-Chain Amino Acid Metabolism in the Pathogenesis of Obesity and Type 2 Diabetes-Related Metabolic Disturbances BCAA Metabolism in Type 2 Diabetes. Nutr. Diabetes 2022;12:35.
    doi: 10.1038/s41387-022-00213-3pmc: PMC9356071pubmed: 35931683google scholar: lookup
  75. Nie C, He T, Zhang W, Zhang G, Ma X. Branched Chain Amino Acids: Beyond Nutrition Metabolism. Int. J. Mol. Sci. 2018;19:954.
    doi: 10.3390/ijms19040954pmc: PMC5979320pubmed: 29570613google scholar: lookup
  76. Wolfson RL, Chantranupong L, Saxton RA, Shen K, Scaria SM, Cantor JR, Sabatini DM. Sestrin2 Is a Leucine Sensor for the MTORC1 Pathway. Science 2016;351:43–48.
    doi: 10.1126/science.aab2674pmc: PMC4698017pubmed: 26449471google scholar: lookup
  77. Calder PC. Branched-Chain Amino Acids and Immunity. J. Nutr. 2006;136:288S–293S.
    doi: 10.1093/jn/136.1.288Spubmed: 16365100google scholar: lookup
  78. Li Z, Zheng W, Kong W, Zeng T. Itaconate: A Potent Macrophage Immunomodulator. Inflammation 2023;46:1177–1191.
    doi: 10.1007/s10753-023-01819-0pmc: PMC10159227pubmed: 37142886google scholar: lookup
  79. O’Neill LAJ, Artyomov MN. Itaconate: The Poster Child of Metabolic Reprogramming in Macrophage Function. Nat. Rev. Immunol. 2019;19:273–281.
    doi: 10.1038/s41577-019-0128-5pubmed: 30705422google scholar: lookup
  80. Peace CG, O’Neill LAJ. The Role of Itaconate in Host Defense and Inflammation. J. Clin. Investig. 2022;132:e148548.
    doi: 10.1172/JCI148548pmc: PMC8759771pubmed: 35040439google scholar: lookup
  81. Lampropoulou V, Sergushichev A, Bambouskova M, Nair S, Vincent EE, Loginicheva E, Cervantes-Barragan L, Ma X, Huang SCC, Griss T. Itaconate Links Inhibition of Succinate Dehydrogenase with Macrophage Metabolic Remodeling and Regulation of Inflammation. Cell Metab. 2016;24:158–166.
    doi: 10.1016/j.cmet.2016.06.004pmc: PMC5108454pubmed: 27374498google scholar: lookup
  82. Mills EL, Ryan DG, Prag HA, Dikovskaya D, Menon D, Zaslona Z, Jedrychowski MP, Costa ASH, Higgins M, Hams E. Itaconate Is an Anti-Inflammatory Metabolite That Activates Nrf2 via Alkylation of KEAP1. Nature 2018;556:113–117.
    doi: 10.1038/nature25986pmc: PMC6047741pubmed: 29590092google scholar: lookup
  83. Bambouskova M, Gorvel L, Lampropoulou V, Sergushichev A, Loginicheva E, Johnson K, Korenfeld D, Mathyer ME, Kim H, Huang LH. Electrophilic Properties of Itaconate and Derivatives Regulate the IκBζ-ATF3 Inflammatory Axis. Nature 2018;556:501–504.
    doi: 10.1038/s41586-018-0052-zpmc: PMC6037913pubmed: 29670287google scholar: lookup
  84. Hooftman A, Angiari S, Hester S, Corcoran SE, Runtsch MC, Ling C, Ruzek MC, Slivka PF, McGettrick AF, Banahan K. The Immunomodulatory Metabolite Itaconate Modifies NLRP3 and Inhibits Inflammasome Activation. Cell Metab. 2020;32:468–478.e7.
    doi: 10.1016/j.cmet.2020.07.016pmc: PMC7422798pubmed: 32791101google scholar: lookup
  85. Tomlinson KL, Riquelme SA, Baskota SU, Drikic M, Monk IR, Stinear TP, Lewis IA, Prince AS. Staphylococcus aureus Stimulates Neutrophil Itaconate Production That Suppresses the Oxidative Burst. Cell Rep. 2023;42:112064.
    doi: 10.1016/j.celrep.2023.112064pmc: PMC10387506pubmed: 36724077google scholar: lookup
  86. Wang C, Wen J, Yan Z, Zhou Y, Gong Z, Luo Y, Li Z, Zheng K, Zhang H, Ding N. Suppressing Neutrophil Itaconate Production Attenuates Mycoplasma Pneumoniae Pneumonia. PLoS Pathog. 2024;20:e1012614.
    doi: 10.1371/journal.ppat.1012614pmc: PMC11567624pubmed: 39499730google scholar: lookup
  87. Crossley JL, Ostashevskaya-Gohstand S, Comazzetto S, Hook JS, Guo L, Vishlaghi N, Juan C, Xu L, Horswill AR, Hoxhaj G. Itaconate-Producing Neutrophils Regulate Local and Systemic Inflammation Following Trauma. JCI Insight 2023;8:e169208.
    doi: 10.1172/jci.insight.169208pmc: PMC10619500pubmed: 37707952google scholar: lookup
  88. Frohnert BI, Jacobs DR, Steinberger J, Moran A, Steffen LM, Sinaiko AR. Relation between Serum Free Fatty Acids and Adiposity, Insulin Resistance, and Cardiovascular Risk Factors from Adolescence to Adulthood. Diabetes 2013;62:3163–3169.
    doi: 10.2337/db12-1122pmc: PMC3749355pubmed: 23670973google scholar: lookup
  89. Alarcón P, Manosalva C, Quiroga J, Belmar I, Álvarez K, Díaz G, Taubert A, Hermosilla C, Carretta MD, Burgos RA. Oleic and Linoleic Acids Induce the Release of Neutrophil Extracellular Traps via Pannexin 1-Dependent ATP Release and P2X1 Receptor Activation. Front. Vet. Sci. 2020;7:260.
    doi: 10.3389/fvets.2020.00260pmc: PMC7291836pubmed: 32582772google scholar: lookup
  90. Khan MA, Pace-Asciak C, Al-Hassan JM, Afzal M, Liu YF, Oommen S, Paul BM, Nair D, Palaniyar N. Furanoid F-Acid F6 Uniquely Induces NETosis Compared to C16 and C18 Fatty Acids in Human Neutrophils. Biomolecules 2018;8:144.
    doi: 10.3390/biom8040144pmc: PMC6315434pubmed: 30428625google scholar: lookup
  91. Rodrigues HG, Vinolo MAR, Magdalon J, Fujiwara H, Cavalcanti DMH, Farsky SHP, Calder PC, Hatanaka E, Curi R. Dietary Free Oleic and Linoleic Acid Enhances Neutrophil Function and Modulates the Inflammatory Response in Rats. Lipids 2010;45:809–819.
    doi: 10.1007/s11745-010-3461-9pubmed: 20730605google scholar: lookup
  92. Wanten GJA, Janssen FP, Naber AHJ. Saturated Triglycerides and Fatty Acids Activate Neutrophils Depending on Carbon Chain-Length. Eur. J. Clin. Investig. 2002;32:285–289.
    doi: 10.1046/j.1365-2362.2002.00959.xpubmed: 11952815google scholar: lookup
  93. Bowers E, Entrup GP, Islam M, Mohan R, Lerner A, Mancuso P, Moore BB, Singer K. High Fat Diet Feeding Impairs Neutrophil Phagocytosis, Bacterial Killing, and Neutrophil-Induced Hematopoietic Regeneration. J. Immunol. 2025;214:680–693.
    doi: 10.1093/jimmun/vkaf024pmc: PMC12041776pubmed: 40094316google scholar: lookup
  94. Brotfain E, Hadad N, Shapira Y, Avinoah E, Zlotnik A, Raichel L, Levy R. Neutrophil Functions in Morbidly Obese Subjects. Clin. Exp. Immunol. 2015;181:156–163.
    doi: 10.1111/cei.12631pmc: PMC4469166pubmed: 25809538google scholar: lookup
  95. Sanchez-pino MD, Richardson WS, Zabaleta J, Puttalingaiah T, Chapple AG, Liu J, Kim Y, Ponder M, Dearmitt R, Baiamonte B. Articles Increased in Fl Ammatory Low-Density Neutrophils in Severe Obesity and Effect of Bariatric Surgery: Results from Case-Control and Prospective Cohort Studies. eBioMedicine 2022;77:103910.
    doi: 10.1016/j.ebiom.2022.103910pmc: PMC8897585pubmed: 35248994google scholar: lookup
  96. Uribe-Querol E, Rosales C. Neutrophils Actively Contribute to Obesity-Associated Inflammation and Pathological Complications. Cells 2022;11:1883.
    doi: 10.3390/cells11121883pmc: PMC9221045pubmed: 35741012google scholar: lookup

Citations

This article has been cited 0 times.
Subscribe to our newsletter
Join 99,357 horse owners like you who receive our email updates on horse health and nutrition.