{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T18:43:10Z","timestamp":1776451390197,"version":"3.51.2"},"reference-count":46,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T00:00:00Z","timestamp":1752710400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Military Operational Medicine Research Program at the United States Army Medical Research and Development Command"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Blast-induced polytrauma (BIPT) is a common injury among military personnel exposed to explosive blasts. It is increasingly recognized as a complex, multisystem disorder that extends beyond neurological damage to include systemic metabolic and inflammatory dysfunction. Adipokines, particularly leptin and adiponectin, are hormones secreted by adipose tissue and are emerging as key mediators in the pathophysiology of traumatic brain injuries. Yet, their long-term dynamics following blast exposure remain unclear. This study investigated the temporal profiles of plasma leptin and adiponectin in a longitudinal rat model of BIPT. Adult male Sprague Dawley rats were subjected to either a single (B) or repeated (BB) blast exposure (20 psi) or served as sham controls. Plasma samples were collected at 24 h, 1 month, 6 months, and 12 months post-exposure, and adipokine levels were measured using Enzyme-linked Immunosorbent Assay. Adiponectin levels exhibited a biphasic response: both B and BB groups showed significant early decrease at 24 h and 1 month compared to sham animals, followed by robust elevation at 6 and 12 months, particularly in the repeated blast group. In contrast, leptin levels remained unchanged acutely but rose significantly at 6 and 12 months post-blast, with the BB group again showing the highest levels. These patterns indicate sustained, exposure-dependent dysregulation of adipokine signaling after blast trauma. The study provides the first longitudinal profile of systemic adipokine responses to BIPT, revealing their potential as accessible biomarkers and therapeutic targets. These findings support a model of chronic metabolic and inflammatory imbalance in BIPT and warrant further investigation in human cohorts and mechanistic studies.<\/jats:p>","DOI":"10.3390\/ijms26146860","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T11:25:17Z","timestamp":1752751517000},"page":"6860","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Longitudinal Dysregulation of Adiponectin and Leptin Following Blast-Induced Polytrauma in a Rat Model"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5760-9437","authenticated-orcid":false,"given":"Rex Jeya Rajkumar Samdavid","family":"Thanapaul","sequence":"first","affiliation":[{"name":"Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4739-648X","authenticated-orcid":false,"given":"Manoj","family":"Govindarajulu","sequence":"additional","affiliation":[{"name":"Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chetan","family":"Pundkar","sequence":"additional","affiliation":[{"name":"Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5733-1760","authenticated-orcid":false,"given":"Gaurav","family":"Phuyal","sequence":"additional","affiliation":[{"name":"Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0155-1131","authenticated-orcid":false,"given":"Ondine","family":"Eken","sequence":"additional","affiliation":[{"name":"Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8988-4628","authenticated-orcid":false,"given":"Joseph B","family":"Long","sequence":"additional","affiliation":[{"name":"Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peethambaran","family":"Arun","sequence":"additional","affiliation":[{"name":"Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1089\/neur.2024.0001","article-title":"Twenty Years of Blast-Induced Neurotrauma: Current State of Knowledge","volume":"5","author":"Sachdeva","year":"2024","journal-title":"Neurotrauma Rep."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Wang, Z., and Jiang, J. (2023). Stress Disorder After Blast Injury. Explosive Blast Injuries: Principles and Practices, Springer Nature.","DOI":"10.1007\/978-981-19-2856-7"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Chan, A., Ouyang, J., Nguyen, K., Jones, A., Basso, S., and Karasik, R. (2024). Traumatic Brain Injuries: A Neuropsychological Review. Front. Behav. Neurosci., 18.","DOI":"10.3389\/fnbeh.2024.1326115"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s11011-024-01524-3","article-title":"Metabolic Disorders after Traumatic Brain Injury: A Narrative Review of Systemic Consequences","volume":"40","author":"Kursancew","year":"2025","journal-title":"Metab. Brain Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"38","DOI":"10.4103\/1673-5374.343891","article-title":"Adipose Tissue, Systematic Inflammation, and Neurodegenerative Diseases","volume":"18","author":"Boleti","year":"2023","journal-title":"Neural Regen. Res."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Huber, K., Szerenos, E., Lewandowski, D., Toczylowski, K., and Sulik, A. (2023). The Role of Adipokines in the Pathologies of the Central Nervous System. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241914684"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Casado, M.E., Collado-P\u00e9rez, R., Frago, L.M., and Barrios, V. (2023). Recent Advances in the Knowledge of the Mechanisms of Leptin Physiology and Actions in Neurological and Metabolic Pathologies. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021422"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Baldelli, S., Aiello, G., Mansilla Di Martino, E., Campaci, D., Muthanna, F.M.S., and Lombardo, M. (2024). The Role of Adipose Tissue and Nutrition in the Regulation of Adiponectin. Nutrients, 16.","DOI":"10.3390\/nu16152436"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1093\/milmed\/usae268","article-title":"Lipidomic Analysis Reveals Systemic Alterations in Servicemen Exposed to Repeated Occupational Low-Level Blast Waves","volume":"190","author":"Arora","year":"2025","journal-title":"Mil. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1007\/s11682-024-00927-1","article-title":"Metabolic Syndrome Is Associated with Reduced Default Mode Network Functional Connectivity in Young Post-9\/11 Veterans","volume":"18","author":"Knoff","year":"2024","journal-title":"Brain Imaging Behav."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/s00018-022-04234-0","article-title":"Adipose Tissue: A Neglected Organ in the Response to Severe Trauma?","volume":"79","author":"Wrba","year":"2022","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"169","DOI":"10.2337\/dbi23-0005","article-title":"Adipose Signals Regulating Distal Organ Health and Disease","volume":"73","author":"Gilani","year":"2024","journal-title":"Diabetes"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e18761429308567","DOI":"10.2174\/0118761429308567240806111848","article-title":"Adipose Tissue Dysfunction Following Trauma and Hypoxia Increases the Risk of Post-Surgical Adhesion: Potential for Therapeutic Interventions","volume":"17","author":"Khodashahi","year":"2024","journal-title":"Curr. Mol. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Gomez-Pinilla, F., and Myers, S.K. (2025). Traumatic Brain Injury from a Peripheral Axis Perspective: Uncovering the Roles of Liver and Adipose Tissue in Temperature Regulation. Prog. Neurobiol., 247.","DOI":"10.1016\/j.pneurobio.2025.102733"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"E1","DOI":"10.1152\/ajpendo.00562.2007","article-title":"Postburn Trauma Insulin Resistance and Fat Metabolism","volume":"294","author":"Cree","year":"2008","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1097\/HTR.0000000000000874","article-title":"The Impact of Blast Exposure\u2014With or without Traumatic Brain Injury\u2014On Metabolic Abnormalities in Post-9\/11 Veterans","volume":"38","author":"Lendvai","year":"2023","journal-title":"J. Head Trauma Rehabil."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.ypmed.2011.07.001","article-title":"BMI Trajectory Groups in Veterans of the Iraq and Afghanistan Wars","volume":"53","author":"Rosenberger","year":"2011","journal-title":"Prev. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1089\/neu.2014.3786","article-title":"Chronic Hormonal Imbalance and Adipose Redistribution Is Associated with Hypothalamic Neuropathology Following Blast Exposure","volume":"33","author":"VandeVord","year":"2016","journal-title":"J. Neurotrauma"},{"key":"ref_19","first-page":"134ra60","article-title":"Chronic Traumatic Encephalopathy in Blast-Exposed Military Veterans and a Blast Neurotrauma Mouse Model","volume":"4","author":"Goldstein","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1089\/neu.2019.6591","article-title":"Long-Term Effects of Blast Exposure: A Functional Study in Rats Using an Advanced Blast Simulator","volume":"37","author":"Arun","year":"2020","journal-title":"J. Neurotrauma"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1016\/j.exger.2004.03.024","article-title":"Circulating Adiponectin Levels Increase in Rats on Caloric Restriction: The Potential for Insulin Sensitization","volume":"39","author":"Zhu","year":"2004","journal-title":"Exp. Gerontol."},{"key":"ref_22","first-page":"349","article-title":"Decrease in Plasma Adiponectin Level and Increase in Adiponectin Immunoreactivity in Cortex and Hippocampus after Traumatic Brain Injury in Rats","volume":"23","author":"Takeuchi","year":"2013","journal-title":"Turk. Neurosurg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.brainres.2009.08.039","article-title":"Pathophysiological Dual Action of Adiponectin after Transient Focal Ischemia in Mouse Brain","volume":"1297","author":"Yatomi","year":"2009","journal-title":"Brain Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1080\/02688697.2019.1578862","article-title":"The Emerging Role of Leptin, Adiponectin and Visfatin in Ischemic\/Hemorrhagic Stroke","volume":"33","author":"Ilhan","year":"2019","journal-title":"Br. J. Neurosurg."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"437","DOI":"10.2174\/1567202617666200603150901","article-title":"Adipokines as Potential Biomarkers in the Neurorehabilitation of Obese Stroke Patients","volume":"17","author":"Ciancarelli","year":"2020","journal-title":"Curr. Neurovasc. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1016\/0006-2952(85)90513-1","article-title":"Glucuronidation and Sulfation in the Rat in Vivo. The Role of the Liver and the Intestine in the in Vivo Clearance of 4-Methylumbelliferone","volume":"34","author":"Mulder","year":"1985","journal-title":"Biochem. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Carbone, G., Bencivenga, L., Santoro, M.A., De Lucia, N., Palaia, M.E., Ercolano, E., Scognamiglio, F., Edison, P., Ferrara, N., and Vitale, D.F. (2024). Impact of Serum Leptin and Adiponectin Levels on Brain Infarcts in Patients with Mild Cognitive Impairment and Alzheimer\u2019s Disease: A Longitudinal Analysis. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1389014"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Khoramipour, K., Chamari, K., Hekmatikar, A.A., Ziyaiyan, A., Taherkhani, S., Elguindy, N.M., and Bragazzi, N.L. (2021). Adiponectin: Structure, Physiological Functions, Role in Diseases, and Effects of Nutrition. Nutrients, 13.","DOI":"10.3390\/nu13041180"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.peptides.2013.08.002","article-title":"Leptin as a Marker for Severity and Prognosis of Aneurysmal Subarachnoid Hemorrhage","volume":"48","author":"Fan","year":"2013","journal-title":"Peptides"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.peptides.2012.03.024","article-title":"Relationship between Plasma Leptin Levels and Clinical Outcomes of Pediatric Traumatic Brain Injury","volume":"35","author":"Lin","year":"2012","journal-title":"Peptides"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/S0025-6196(11)63647-1","article-title":"Paroxysmal Sympathetic Storms (\u201cdiencephalic Seizures\u201d) after Severe Diffuse Axonal Head Injury","volume":"73","author":"Boeve","year":"1998","journal-title":"Mayo Clin. Proc."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"909","DOI":"10.2337\/diab.45.7.909","article-title":"Activation of \u03923 Adrenergic Receptors Suppresses Leptin Expression and Mediates a Leptin-Independent Inhibition of Food Intake in Mice","volume":"45","author":"Mantzoros","year":"1996","journal-title":"Diabetes"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1177\/0148607198022006340","article-title":"Plasma Leptin Levels in Trauma Patients: Effect of Adjuvant Recombinant Human Growth Hormone in Intravenously Fed Multiple Trauma Patients","volume":"22","author":"Jeevanandam","year":"1998","journal-title":"JPEN J. Parenter. Enter. Nutr."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1080\/02699050400024946","article-title":"Heart Rate Variability (HRV) of Patients with Traumatic Brain Injury (TBI) during the Post-Insult Sub-Acute Period","volume":"19","author":"Keren","year":"2005","journal-title":"Brain Inj."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1097\/01.CCM.0000152221.87477.21","article-title":"Influence of Brain Injury on Early Posttraumatic Bone Metabolism","volume":"33","author":"Trentz","year":"2005","journal-title":"Crit. Care Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.bbr.2017.04.025","article-title":"Overpressure Blast Injury-Induced Oxidative Stress and Neuroinflammation Response in Rat Frontal Cortex and Cerebellum","volume":"340","author":"Toklu","year":"2018","journal-title":"Behav. Brain Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3901\/JME.2011.11.007","article-title":"Effect of Leptin on Bone Metabolism in Rat Model of Traumatic Brain Injury and Femoral Fracture","volume":"14","author":"Wang","year":"2011","journal-title":"Chin. J. Traumatol. (Engl. Ed.)"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"12248","DOI":"10.1073\/pnas.1202835109","article-title":"Adiponectin Is Critical in Determining Susceptibility to Depressive Behaviors and Has Antidepressant-like Activity","volume":"109","author":"Liu","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2564","DOI":"10.1089\/neu.2012.2510","article-title":"Blast Exposure Induces Post-Traumatic Stress Disorder-Related Traits in a Rat Model of Mild Traumatic Brain Injury","volume":"29","author":"Elder","year":"2012","journal-title":"J. Neurotrauma"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e2313568121","DOI":"10.1073\/pnas.2313568121","article-title":"Impact of Repeated Blast Exposure on Active-Duty United States Special Operations Forces","volume":"121","author":"Gilmore","year":"2024","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Ravula, A.R., Das, T., Gosain, A., Dolalas, T., Padhi, S., Chandra, N., and Pfister, B.J. (2022). An Update on Repeated Blast Traumatic Brain Injury. Curr. Opin. Biomed. Eng., 24.","DOI":"10.1016\/j.cobme.2022.100409"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Saeedi, M., and Rashidy-Pour, A. (2021). Association between Chronic Stress and Alzheimer\u2019s Disease: Therapeutic Effects of Saffron. Biomed. Pharmacother., 133.","DOI":"10.1016\/j.biopha.2020.110995"},{"key":"ref_43","first-page":"681612","article-title":"Adipokines as Drug Targets in Diabetes and Underlying Disturbances","volume":"2015","year":"2015","journal-title":"J. Diabetes Res."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Arjunan, A., and Song, J. (2023). Pharmacological and Physiological Roles of Adipokines and Myokines in Metabolic-Related Dementia. Biomed. Pharmacother., 163.","DOI":"10.1016\/j.biopha.2023.114847"},{"key":"ref_45","first-page":"e78050","article-title":"The Interplay Between Adipokines and Body Composition in Obesity and Metabolic Diseases","volume":"17","author":"Zadgaonkar","year":"2025","journal-title":"Cureus"},{"key":"ref_46","unstructured":"National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals (2011). Guide for the Care and Use of Laboratory Animals."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/14\/6860\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:11:13Z","timestamp":1760033473000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/14\/6860"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,17]]},"references-count":46,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["ijms26146860"],"URL":"https:\/\/doi.org\/10.3390\/ijms26146860","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,17]]}}}