{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:43:44Z","timestamp":1790401424732,"version":"4.1.0"},"reference-count":73,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Int J Obes"],"published-print":{"date-parts":[[2026,8]]},"DOI":"10.1038\/s41366-026-02130-2","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T13:43:07Z","timestamp":1782740587000},"page":"1686-1697","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Obesity-induced intervertebral disk degeneration: pathophysiology and clinical implications"],"prefix":"10.1038","volume":"50","author":[{"given":"Prahalad Singh","family":"Bharti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priya Kumari","family":"Gorai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harshit","family":"Dutt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yashdeep","family":"Gupta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garima","family":"Malik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neerja","family":"Rani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8320-4871","authenticated-orcid":false,"given":"Vivek","family":"Shankar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,29]]},"reference":[{"key":"2130_CR1","doi-asserted-by":"publisher","first-page":"421","DOI":"10.5455\/medarh.2019.73.421-424","volume":"73","author":"N Kos","year":"2019","unstructured":"Kos N, Gradisnik L, Velnar T. A brief review of the degenerative intervertebral disc disease. Med Arch. 2019;73:421\u20134.","journal-title":"Med Arch"},{"key":"2130_CR2","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1038\/nrendo.2014.124","volume":"10","author":"CS Morgen","year":"2014","unstructured":"Morgen CS, S\u00f8rensen TIA. Global trends in the prevalence of overweight and obesity. Nat Rev Endocrinol. 2014;10:513\u20134.","journal-title":"Nat Rev Endocrinol"},{"key":"2130_CR3","doi-asserted-by":"publisher","first-page":"2627","DOI":"10.1016\/S0140-6736(17)32129-3","volume":"390","author":"L Abarca-G\u00f3mez","year":"2017","unstructured":"Abarca-G\u00f3mez L, Abdeen ZA, Hamid ZA, Abu-Rmeileh NM, Acosta-Cazares B, Acuin C, et al. Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128\u00b79 million children, adolescents, and adults. Lancet. 2017;390:2627\u201342.","journal-title":"Lancet"},{"key":"2130_CR4","first-page":"S42","volume":"157","author":"TM Bellanger","year":"2005","unstructured":"Bellanger TM, Bray GA. Obesity related morbidity and mortality. J La State Med Soc. 2005;157:S42\u201349.","journal-title":"J La State Med Soc"},{"key":"2130_CR5","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2458-9-88","volume":"9","author":"DP Guh","year":"2009","unstructured":"Guh DP, Zhang W, Bansback N, Amarsi Z, Birmingham CL, Anis AH. The incidence of co-morbidities related to obesity and overweight: a systematic review and meta-analysis. BMC Public Health. 2009;9:88.","journal-title":"BMC Public Health"},{"key":"2130_CR6","doi-asserted-by":"publisher","unstructured":"Samanta A, Lufkin T, Kraus P. Intervertebral disc degeneration\u2014Current therapeutic options and challenges. Front Public Health. 2023;11. https:\/\/doi.org\/10.3389\/fpubh.2023.1156749.","DOI":"10.3389\/fpubh.2023.1156749"},{"key":"2130_CR7","doi-asserted-by":"publisher","first-page":"1789","DOI":"10.1016\/S0140-6736(18)32279-7","volume":"392","author":"SL James","year":"2018","unstructured":"James SL, Abate D, Abate KH, Abay SM, Abbafati C, Abbasi N, et al. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990\u20132017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392:1789\u2013858.","journal-title":"Lancet"},{"key":"2130_CR8","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.3224","volume":"36","author":"F Cannata","year":"2020","unstructured":"Cannata F, Vadal\u00e0 G, Ambrosio L, Fallucca S, Napoli N, Papalia R, et al. Intervertebral disc degeneration: a focus on obesity and type 2 diabetes. Diab\/Metab Res Rev. 2020;36:e3224.","journal-title":"Diab\/Metab Res Rev"},{"key":"2130_CR9","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.1016\/j.spinee.2015.02.001","volume":"15","author":"AB Dario","year":"2015","unstructured":"Dario AB, Ferreira ML, Refshauge KM, Lima TS, Ordo\u00f1ana JR, Ferreira PH. The relationship between obesity, low back pain, and lumbar disc degeneration when genetics and the environment are considered: a systematic review of twin studies. Spine J. 2015;15:1106\u201317.","journal-title":"Spine J"},{"key":"2130_CR10","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1111\/obr.12102","volume":"14","author":"BM Popkin","year":"2013","unstructured":"Popkin BM, Slining MM. New dynamics in global obesity facing low- and middle-income countries. Obes Rev. 2013;14:11\u201320.","journal-title":"Obes Rev"},{"key":"2130_CR11","doi-asserted-by":"publisher","first-page":"e009773","DOI":"10.1136\/bmjgh-2022-009773","volume":"7","author":"A Okunogbe","year":"2022","unstructured":"Okunogbe A, Nugent R, Spencer G, Powis J, Ralston J, Wilding J. Economic impacts of overweight and obesity: current and future estimates for 161 countries. BMJ Glob Health. 2022;7:e009773.","journal-title":"BMJ Glob Health"},{"key":"2130_CR12","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/j.wneu.2021.09.066","volume":"157","author":"S Kirnaz","year":"2022","unstructured":"Kirnaz S, Capadona C, Wong T, Goldberg JL, Medary B, Sommer F, et al. Fundamentals of intervertebral disc degeneration. World Neurosurg. 2022;157:264\u201373.","journal-title":"World Neurosurg"},{"key":"2130_CR13","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1093\/aje\/kwp356","volume":"171","author":"R Shiri","year":"2010","unstructured":"Shiri R, Karppinen J, Leino-Arjas P, Solovieva S, Viikari-Juntura E. The association between obesity and low back pain: a meta-analysis. Am J Epidemiol. 2010;171:135\u201354.","journal-title":"Am J Epidemiol"},{"key":"2130_CR14","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1007\/s00586-021-06994-y","volume":"31","author":"Q You","year":"2022","unstructured":"You Q, Jiang Q, Li D, Wang T, Wang S, Cao S. Waist circumference, waist-hip ratio, body fat rate, total body fat mass and risk of low back pain: a systematic review and meta-analysis. Eur Spine J. 2022;31:123\u201335.","journal-title":"Eur Spine J"},{"key":"2130_CR15","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1016\/j.ocl.2011.07.001","volume":"42","author":"N Inoue","year":"2011","unstructured":"Inoue N, Espinoza Or\u00edas AA. Biomechanics of intervertebral disk degeneration. Orthopedic Clin North Am. 2011;42:487\u201399.","journal-title":"Orthopedic Clin North Am"},{"key":"2130_CR16","doi-asserted-by":"publisher","first-page":"168","DOI":"10.12965\/jer.1836070.035","volume":"14","author":"IM da Cruz Fernandes","year":"2018","unstructured":"da Cruz Fernandes IM, Pinto RZ, Ferreira P, Lira FS, Fernandes IM, da C, et al. Low back pain, obesity, and inflammatory markers: exercise as potential treatment. J Exerc Rehabil. 2018;14:168\u201374.","journal-title":"J Exerc Rehabil"},{"key":"2130_CR17","doi-asserted-by":"publisher","first-page":"2030","DOI":"10.3390\/ijms20082030","volume":"20","author":"C Ruiz-Fern\u00e1ndez","year":"2019","unstructured":"Ruiz-Fern\u00e1ndez C, Francisco V, Pino J, Mera A, Gonz\u00e1lez-Gay MA, G\u00f3mez R, et al. Molecular relationships among obesity, inflammation and intervertebral disc degeneration: are adipokines the common link? Int J Mol Sci. 2019;20:2030.","journal-title":"Int J Mol Sci"},{"key":"2130_CR18","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1007\/BF00298361","volume":"1","author":"RD Fraser","year":"1993","unstructured":"Fraser RD, Osti OL, Vernon-Roberts B. Intervertebral disc degeneration. Eur Spine J. 1993;1:205\u201313.","journal-title":"Eur Spine J"},{"key":"2130_CR19","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1007\/s00586-013-2903-5","volume":"23","author":"MC Batti\u00e9","year":"2014","unstructured":"Batti\u00e9 MC, Laz\u00e1ry \u00c1, Fairbank J, Eisenstein S, Heywood C, Brayda-Bruno M, et al. Disc degeneration-related clinical phenotypes. Eur Spine J. 2014;23:305\u201314.","journal-title":"Eur Spine J"},{"key":"2130_CR20","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.116593","volume":"174","author":"Q Xia","year":"2024","unstructured":"Xia Q, Zhao Y, Dong H, Mao Q, Zhu L, Xia J, et al. Progress in the study of molecular mechanisms of intervertebral disc degeneration. Biomed Pharmacother. 2024;174:116593.","journal-title":"Biomed Pharmacother"},{"key":"2130_CR21","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1111\/cpr.12121","volume":"47","author":"SZ Wang","year":"2014","unstructured":"Wang SZ, Rui YF, Lu J, Wang C. Cell and molecular biology of intervertebral disc degeneration: current understanding and implications for potential therapeutic strategies. Cell Prolif. 2014;47:381\u201390.","journal-title":"Cell Prolif"},{"key":"2130_CR22","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/j.arr.2007.08.001","volume":"6","author":"C-Q Zhao","year":"2007","unstructured":"Zhao C-Q, Wang L-M, Jiang L-S, Dai L-Y. The cell biology of intervertebral disc aging and degeneration. Ageing Res Rev. 2007;6:247\u201361.","journal-title":"Ageing Res Rev"},{"key":"2130_CR23","doi-asserted-by":"publisher","first-page":"34","DOI":"10.3390\/medsci6020034","volume":"6","author":"A Sharma","year":"2018","unstructured":"Sharma A. The role of adipokines in intervertebral disc degeneration. Med Sci. 2018;6:34.","journal-title":"Med Sci"},{"key":"2130_CR24","doi-asserted-by":"publisher","first-page":"375","DOI":"10.3390\/ijms22010375","volume":"22","author":"G Curic","year":"2021","unstructured":"Curic G. Intervertebral disc and adipokine leptin\u2014loves me, loves me not. Int J Mol Sci. 2021;22:375.","journal-title":"Int J Mol Sci"},{"key":"2130_CR25","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1042\/CS20200895","volume":"135","author":"EB Taylor","year":"2021","unstructured":"Taylor EB. The complex role of adipokines in obesity, inflammation, and autoimmunity. Clin Sci. 2021;135:731\u201352.","journal-title":"Clin Sci"},{"key":"2130_CR26","doi-asserted-by":"publisher","first-page":"8566","DOI":"10.3390\/ijms24108566","volume":"24","author":"H Ohnishi","year":"2023","unstructured":"Ohnishi H, Zhang Z, Yurube T, Takeoka Y, Kanda Y, Tsujimoto R, et al. Anti-inflammatory effects of adiponectin receptor agonist AdipoRon against intervertebral disc degeneration. Int J Mol Sci. 2023;24:8566.","journal-title":"Int J Mol Sci"},{"key":"2130_CR27","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-12793-2","volume":"12","author":"JH Shin","year":"2022","unstructured":"Shin JH, Park S, Cho H, Kim JH, Choi H. Adipokine human Resistin promotes obesity-associated inflammatory intervertebral disc degeneration via pro-inflammatory cytokine cascade activation. Sci Rep. 2022;12:8936.","journal-title":"Sci Rep"},{"key":"2130_CR28","doi-asserted-by":"publisher","first-page":"334","DOI":"10.3390\/molecules27020334","volume":"27","author":"J-E Kim","year":"2022","unstructured":"Kim J-E, Kim J-S, Jo M-J, Cho E, Ahn S-Y, Kwon Y-J, et al. The roles and associated mechanisms of adipokines in development of metabolic syndrome. Molecules. 2022;27:334.","journal-title":"Molecules"},{"key":"2130_CR29","doi-asserted-by":"publisher","DOI":"10.1038\/srep09102","volume":"5","author":"Y Zhao","year":"2015","unstructured":"Zhao Y, Tian Q, Liu B, Cuellar J, Richbourgh B, Jia T, et al. Progranulin knockout accelerates intervertebral disc degeneration in aging mice. Sci Rep. 2015;5:9102.","journal-title":"Sci Rep"},{"key":"2130_CR30","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.115401","volume":"166","author":"J Yi","year":"2023","unstructured":"Yi J, Zhou Q, Huang J, Niu S, Ji G, Zheng T. Lipid metabolism disorder promotes the development of intervertebral disc degeneration. Biomed Pharmacother. 2023;166:115401.","journal-title":"Biomed Pharmacother"},{"key":"2130_CR31","doi-asserted-by":"publisher","first-page":"1414","DOI":"10.1097\/BRS.0000000000001556","volume":"41","author":"C Liu","year":"2016","unstructured":"Liu C, Yang H, Gao F, Li X, An Y, Wang J, et al. Resistin promotes intervertebral disc degeneration by upregulation of ADAMTS-5 through p38 MAPK signaling pathway. Spine. 2016;41:1414.","journal-title":"Spine"},{"key":"2130_CR32","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1080\/21623945.2021.1910155","volume":"10","author":"H Cui","year":"2021","unstructured":"Cui H, Du X, Liu C, Chen S, Cui H, Liu H, et al. Visfatin promotes intervertebral disc degeneration by inducing IL-6 expression through the ERK\/JNK\/p38 signalling pathways. Adipocyte. 2021;10:201\u201315.","journal-title":"Adipocyte"},{"key":"2130_CR33","doi-asserted-by":"publisher","first-page":"11732","DOI":"10.18632\/aging.103339","volume":"12","author":"S Hu","year":"2020","unstructured":"Hu S, Shao Z, Zhang C, Chen L, Mamun AA, Zhao N, et al. Chemerin facilitates intervertebral disc degeneration via TLR4 and CMKLR1 and activation of NF-kB signaling pathway. Aging. 2020;12:11732\u201353.","journal-title":"Aging"},{"key":"2130_CR34","doi-asserted-by":"publisher","DOI":"10.1016\/j.archger.2022.104748","volume":"102","author":"VLF Cabral","year":"2022","unstructured":"Cabral VLF, Wang F, Peng X, Gao J, Zhou Z, Sun R, et al. Omentin-1 promoted proliferation and ameliorated inflammation, apoptosis, and degeneration in human nucleus pulposus cells. Arch Gerontol Geriatrics. 2022;102:104748.","journal-title":"Arch Gerontol Geriatrics"},{"key":"2130_CR35","doi-asserted-by":"publisher","first-page":"13849","DOI":"10.1080\/21655979.2022.2084495","volume":"13","author":"X Huang","year":"2022","unstructured":"Huang X, Chen C, Chen Y, Xu J, Liu L. Omentin-1 alleviate interleukin-1\u03b2(IL-1\u03b2)-induced nucleus pulposus cells senescence. Bioengineered. 2022;13:13849\u201359.","journal-title":"Bioengineered"},{"key":"2130_CR36","doi-asserted-by":"crossref","unstructured":"Chung HS, Choi KM. Chapter Six - Organokines in disease. In: Makowski GS, editor. Advances in Clinical Chemistry. Elsevier; 2020. pp.261\u2013321.","DOI":"10.1016\/bs.acc.2019.07.012"},{"key":"2130_CR37","doi-asserted-by":"publisher","unstructured":"He Y, Liu S, Lin H, Ding F, Shao Z, Xiong L. Roles of organokines in intervertebral disc homeostasis and degeneration. Front Endocrinol. 2024;15. https:\/\/doi.org\/10.3389\/fendo.2024.1340625.","DOI":"10.3389\/fendo.2024.1340625"},{"key":"2130_CR38","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3803\/EnM.2016.31.1.1","volume":"31","author":"KM Choi","year":"2016","unstructured":"Choi KM. The impact of organokines on insulin resistance, inflammation, and atherosclerosis. Endocrinol Metab. 2016;31:1\u20136.","journal-title":"Endocrinol Metab"},{"key":"2130_CR39","doi-asserted-by":"publisher","first-page":"91887","DOI":"10.18632\/oncotarget.19695","volume":"8","author":"W Li","year":"2017","unstructured":"Li W, Wu X, Qu R, Wang W, Chen X, Cheng L, et al. Ghrelin protects against nucleus pulposus degeneration through inhibition of NF-\u03baB signaling pathway and activation of Akt signaling pathway. Oncotarget. 2017;8:91887\u2013901.","journal-title":"Oncotarget"},{"key":"2130_CR40","doi-asserted-by":"publisher","first-page":"3681","DOI":"10.1111\/jcmm.17944","volume":"27","author":"J Sun","year":"2023","unstructured":"Sun J, Tan Y, Su J, Mikhail H, Pavel V, Deng Z, et al. Role and molecular mechanism of ghrelin in degenerative musculoskeletal disorders. J Cell Mol Med. 2023;27:3681\u201391.","journal-title":"J Cell Mol Med"},{"key":"2130_CR41","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/cddiscovery.2016.107","volume":"3","author":"X Wu","year":"2017","unstructured":"Wu X, Song Y, Liu W, Wang K, Gao Y, Li S, et al. IAPP modulates cellular autophagy, apoptosis, and extracellular matrix metabolism in human intervertebral disc cells. Cell Death Discov. 2017;3:1\u201312.","journal-title":"Cell Death Discov"},{"key":"2130_CR42","doi-asserted-by":"publisher","first-page":"1479","DOI":"10.1016\/j.bbadis.2017.04.016","volume":"1863","author":"X Wu","year":"2017","unstructured":"Wu X, Wang K, Hua W, Li S, Liu X, Liu W, et al. Down-regulation of islet amyloid polypeptide expression induces death of human annulus fibrosus cells via mitochondrial and death receptor pathways. Biochim Biophys Acta Mol Basis Dis. 2017;1863:1479\u201391.","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"2130_CR43","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/j.freeradbiomed.2021.10.034","volume":"177","author":"Y Peng","year":"2021","unstructured":"Peng Y, Lin H, Tian S, Liu S, Li J, Lv X, et al. Glucagon-like peptide-1 receptor activation maintains extracellular matrix integrity by inhibiting the activity of mitogen-activated protein kinases and activator protein-1. Free Radic Biol Med. 2021;177:247\u201359.","journal-title":"Free Radic Biol Med"},{"key":"2130_CR44","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1007\/s00586-006-0171-3","volume":"15","author":"D Chan","year":"2006","unstructured":"Chan D, Song Y, Sham P, Cheung KMC. Genetics of disc degeneration. Eur Spine J. 2006;15:317\u201325.","journal-title":"Eur Spine J"},{"key":"2130_CR45","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/j.gendis.2016.04.005","volume":"3","author":"Y Feng","year":"2016","unstructured":"Feng Y, Egan B, Wang J. Genetic factors in intervertebral disc degeneration. Genes Dis. 2016;3:178\u201385.","journal-title":"Genes Dis"},{"key":"2130_CR46","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2023.101902","volume":"87","author":"L Kang","year":"2023","unstructured":"Kang L, Zhang H, Jia C, Zhang R, Shen C. Epigenetic modifications of inflammation in intervertebral disc degeneration. Ageing Res Rev. 2023;87:101902.","journal-title":"Ageing Res Rev"},{"key":"2130_CR47","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1590\/S1413-78522007000100002","volume":"15","author":"FTB Nunes","year":"2007","unstructured":"Nunes FTB, Conforti-Froes NDT, Negrelli WF, Souza DRS. Genetic and environmental factors involved on intervertebral disc degeneration. Acta ortop bras. 2007;15:9\u201313.","journal-title":"Acta ortop bras"},{"key":"2130_CR48","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1054\/mehy.2000.1253","volume":"56","author":"RR Fogelholm","year":"2001","unstructured":"Fogelholm RR, Alho AV. Smoking and intervertebral disc degeneration. Med Hypotheses. 2001;56:537\u20139.","journal-title":"Med Hypotheses"},{"key":"2130_CR49","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.spinee.2023.10.021","volume":"24","author":"W Guo","year":"2024","unstructured":"Guo W, Li B-L, Zhao J-Y, Li X-M, Wang L-F. Causal associations between modifiable risk factors and intervertebral disc degeneration. Spine J. 2024;24:195\u2013209.","journal-title":"Spine J"},{"key":"2130_CR50","doi-asserted-by":"publisher","first-page":"891","DOI":"10.2106\/JBJS.23.00902","volume":"106","author":"L Szigethy","year":"2024","unstructured":"Szigethy L, Sigmundsson FG, Joelson A. Surgically treated degenerative lumbar spine diseases in twins. JBJS. 2024;106:891.","journal-title":"JBJS"},{"key":"2130_CR51","doi-asserted-by":"publisher","first-page":"1740","DOI":"10.1136\/ard.2010.137836","volume":"70","author":"G Livshits","year":"2011","unstructured":"Livshits G, Popham M, Malkin I, Sambrook PN, MacGregor AJ, Spector T, et al. Lumbar disc degeneration and genetic factors are the main risk factors for low back pain in women: the UK Twin Spine Study. Ann Rheum Dis. 2011;70:1740\u20135.","journal-title":"Ann Rheum Dis"},{"key":"2130_CR52","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.3390\/biom11091279","volume":"11","author":"VV Trefilova","year":"2021","unstructured":"Trefilova VV, Shnayder NA, Petrova MM, Kaskaeva DS, Tutynina OV, Petrov KV, et al. The role of polymorphisms in collagen-encoding genes in intervertebral disc degeneration. Biomolecules. 2021;11:1279.","journal-title":"Biomolecules"},{"key":"2130_CR53","doi-asserted-by":"publisher","DOI":"10.1186\/s13018-021-02724-8","volume":"16","author":"G Xie","year":"2021","unstructured":"Xie G, Liang C, Yu H, Zhang Q. Association between polymorphisms of collagen genes and susceptibility to intervertebral disc degeneration: a meta-analysis. J Orthop Surg Res. 2021;16:616.","journal-title":"J Orthop Surg Res"},{"key":"2130_CR54","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1007\/s00701-010-0831-2","volume":"153","author":"NK Kim","year":"2011","unstructured":"Kim NK, Shin DA, Han IB, Yoo EH, Kim SH, Chung SS. The association of aggrecan gene polymorphism with the risk of intervertebral disc degeneration. Acta Neurochir. 2011;153:129\u201333.","journal-title":"Acta Neurochir"},{"key":"2130_CR55","doi-asserted-by":"publisher","first-page":"1","DOI":"10.22203\/eCM.v011a01","volume":"11","author":"P Roughley","year":"2006","unstructured":"Roughley P, Martens D, Rantakokko J, Alini M, Mwale F, Antoniou J. The involvement of aggrecan polymorphism in degeneration of human intervertebral disc and articular cartilage. Eur Cell Mater. 2006;11:1\u20137.","journal-title":"Eur Cell Mater"},{"key":"2130_CR56","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.110660","volume":"131","author":"Y Wang","year":"2020","unstructured":"Wang Y, Che M, Xin J, Zheng Z, Li J, Zhang S. The role of IL-1\u03b2 and TNF-\u03b1 in intervertebral disc degeneration. Biomed Pharmacother. 2020;131:110660.","journal-title":"Biomed Pharmacother"},{"key":"2130_CR57","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2023.112181","volume":"177","author":"H Li","year":"2023","unstructured":"Li H, Wang X, Pan H, Xiao C, Wang C, Guo S, et al. The mechanisms and functions of IL-1\u03b2 in intervertebral disc degeneration. Exp Gerontol. 2023;177:112181.","journal-title":"Exp Gerontol"},{"key":"2130_CR58","doi-asserted-by":"publisher","first-page":"738","DOI":"10.1002\/ca.23877","volume":"35","author":"PA P\u0119kala","year":"2022","unstructured":"P\u0119kala PA, Jasi\u0144ska M, Taterra D, Skoczen KM, Jarosz A, Konopka T, et al. Vitamin D receptor gene polymorphism influence on lumbar intervertebral disc degeneration. Clin Anat. 2022;35:738\u201344.","journal-title":"Clin Anat"},{"key":"2130_CR59","doi-asserted-by":"publisher","first-page":"e25922","DOI":"10.1097\/MD.0000000000025922","volume":"100","author":"J Xue","year":"2021","unstructured":"Xue J, Song Y, Liu H, Liu L, Li T, Gong Q. Vitamin D receptor gene polymorphisms and risk of intervertebral disc degeneration: an updated meta-analysis based on 23 studies. Medicine. 2021;100:e25922.","journal-title":"Medicine"},{"key":"2130_CR60","doi-asserted-by":"publisher","first-page":"12275","DOI":"10.3390\/ijms232012275","volume":"23","author":"H-H Chen","year":"2022","unstructured":"Chen H-H, Hsu H-T, Liao M-H, Teng M-S. Effects of sex and obesity on LEP variant and leptin level associations in intervertebral disc degeneration. Int J Mol Sci. 2022;23:12275.","journal-title":"Int J Mol Sci"},{"key":"2130_CR61","doi-asserted-by":"publisher","first-page":"1340","DOI":"10.3892\/etm.2014.1909","volume":"8","author":"OF Khabour","year":"2014","unstructured":"Khabour OF, Abu\u2011Rumeh L, Al\u2011Jarrah M, Jamous M, Alhashimi F. Association of adiponectin protein and ADIPOQ gene variants with lumbar disc degeneration. Exp Therapeutic Med. 2014;8:1340\u20134.","journal-title":"Exp Therapeutic Med"},{"key":"2130_CR62","doi-asserted-by":"publisher","first-page":"5598","DOI":"10.12659\/MSM.911101","volume":"24","author":"J Chen","year":"2018","unstructured":"Chen J, Zhu Q, Liu G, Yang X, Zhao S, Chen W, et al. Fat mass and obesity-associated (FTO) gene polymorphisms are associated with risk of intervertebral disc degeneration in chinese han population: a case control study. Med Sci Monit. 2018;24:5598\u2013609.","journal-title":"Med Sci Monit"},{"key":"2130_CR63","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1089\/gtmb.2013.0225","volume":"17","author":"Z Wu","year":"2013","unstructured":"Wu Z, Yang Y, Qiu G. Association study between the polymorphisms of the fat mass- and obesity-associated gene with the risk of intervertebral disc degeneration in the Han Chinese population. Genet Test Mol Biomark. 2013;17:756\u201362.","journal-title":"Genet Test Mol Biomark"},{"key":"2130_CR64","doi-asserted-by":"publisher","unstructured":"Zhou J, Mi J, Peng Y, Han H, Liu Z. Causal associations of obesity with the intervertebral degeneration, low back pain, and sciatica: a two-sample Mendelian randomization study. Front Endocrinol. 2021;12. https:\/\/doi.org\/10.3389\/fendo.2021.740200.","DOI":"10.3389\/fendo.2021.740200"},{"key":"2130_CR65","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1038\/s41366-024-01706-0","volume":"49","author":"B Galuppo","year":"2025","unstructured":"Galuppo B, Mannam P, Bonet J, Pierpont B, Trico\u2019 D, Haskell-Luevano C, et al. Rare variants in the melanocortin 4 receptor gene (MC4R) are associated with abdominal fat and insulin resistance in youth with obesity. Int J Obes. 2025;49:819\u201326.","journal-title":"Int J Obes"},{"key":"2130_CR66","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1038\/ng.140","volume":"40","author":"RJF Loos","year":"2008","unstructured":"Loos RJF, Lindgren CM, Li S, Wheeler E, Zhao JH, Prokopenko I, et al. Common variants near MC4R are associated with fat mass, weight and risk of obesity. Nat Genet. 2008;40:768\u201375.","journal-title":"Nat Genet"},{"key":"2130_CR67","doi-asserted-by":"publisher","DOI":"10.1155\/2007\/95974","volume":"2007","author":"R Stienstra","year":"2007","unstructured":"Stienstra R, Duval C, M\u00fcller M, Kersten S. PPARs, obesity, and inflammation. PPAR Res. 2007;2007:095974.","journal-title":"PPAR Res"},{"key":"2130_CR68","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28167-1","volume":"13","author":"G Bjornsdottir","year":"2022","unstructured":"Bjornsdottir G, Stefansdottir L, Thorleifsson G, Sulem P, Norland K, Ferkingstad E, et al. Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology. Nat Commun. 2022;13:634.","journal-title":"Nat Commun"},{"key":"2130_CR69","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-71891-5","volume":"14","author":"C Shi","year":"2024","unstructured":"Shi C, Fan Y, Huang X, Fan M, Zhao L, Zhang H, et al. Single-cell RNA sequencing reveals the differentiation and regulation of endplate cells in human intervertebral disc degeneration. Sci Rep. 2024;14:21414.","journal-title":"Sci Rep"},{"key":"2130_CR70","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2024.102323","volume":"98","author":"X Chen","year":"2024","unstructured":"Chen X, Zhang A, Zhao K, Gao H, Shi P, Chen Y, et al. The role of oxidative stress in intervertebral disc degeneration: mechanisms and therapeutic implications. Ageing Res Rev. 2024;98:102323.","journal-title":"Ageing Res Rev"},{"key":"2130_CR71","doi-asserted-by":"publisher","unstructured":"Li S, Du J, Huang Y, Gao S, Zhao Z, Chang Z, et al. From hyperglycemia to intervertebral disc damage: exploring diabetic-induced disc degeneration. Front Immunol. 2024;15. https:\/\/doi.org\/10.3389\/fimmu.2024.1355503.","DOI":"10.3389\/fimmu.2024.1355503"},{"key":"2130_CR72","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1308\/003588410X12518836438967","volume":"92","author":"J Mangwani","year":"2010","unstructured":"Mangwani J, Giles C, Mullins M, Salih T, Natali C. Obesity and recovery from low back pain: a prospective study to investigate the effect of body mass index on recovery from low back pain. annals. 2010;92:23\u20136.","journal-title":"annals"},{"key":"2130_CR73","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1097\/BRS.0b013e3182647af2","volume":"38","author":"I Heuch","year":"2013","unstructured":"Heuch I, Heuch I, Hagen K, Zwart J-A. Body mass index as a risk factor for developing chronic low back pain: a follow-up in the Nord-Tr\u00f8ndelag Health Study. Spine. 2013;38:133.","journal-title":"Spine"}],"container-title":["International Journal of Obesity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41366-026-02130-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41366-026-02130-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41366-026-02130-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T18:02:45Z","timestamp":1786471365000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41366-026-02130-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,29]]},"references-count":73,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["2130"],"URL":"https:\/\/doi.org\/10.1038\/s41366-026-02130-2","relation":{},"ISSN":["0307-0565","1476-5497"],"issn-type":[{"value":"0307-0565","type":"print"},{"value":"1476-5497","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,29]]},"assertion":[{"value":"7 March 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 May 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 June 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 June 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}]}}