{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T13:49:14Z","timestamp":1761745754465,"version":"build-2065373602"},"reference-count":112,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Recent studies show that obesity significantly increases disease severity and progression in several forms of inflammatory arthritis, including rheumatoid arthritis (RA), psoriatic arthritis (PsA) and gout. Obesity increases the risk for developing inflammatory arthritis. Similarly, obesity negatively impacts disease severity and treatment outcomes. The underlying mechanisms driving these relationships are not fully understood. One emerging area of investigation is the role of the lymphatic vasculature. Obesity profoundly impacts lymphatic function. Excess adipose tissue can compress and disrupt lymphatic vessels, leading to impaired flow and drainage. Additionally, obesity-associated inflammation and metabolic dysregulation have been linked to lymphatic endothelial cell dysfunction, further compromising transport and immunoregulatory capacities. This impairment fosters an environment for the accumulation of inflammatory cells and mediators, sustaining chronic inflammation. In this review, we will provide new perspectives on the detrimental triangle of obesity, lymphatic dysfunction, and inflammation in chronic inflammatory arthritis and find new starting points for therapeutics.<\/jats:p>","DOI":"10.3390\/jcm14217641","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T09:16:24Z","timestamp":1761729384000},"page":"7641","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Lymphatic Perspective on Obesity and Inflammatory Arthritis: New Disease-Modifying Potential in Rheumatology"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4618-6827","authenticated-orcid":false,"given":"Hannah","family":"den Braanker","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Maasstad Hospital, 3079 DZ Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5134-5453","authenticated-orcid":false,"given":"Eline S.","family":"van der Valk","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Erasmus Medical Centre, 3015 GD Rotterdam, The Netherlands"},{"name":"Department of Endocrinology, Utrecht University Medical Centre, 3584 CX Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4041-3411","authenticated-orcid":false,"given":"Radjesh J.","family":"Bisoendial","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Maasstad Hospital, 3079 DZ Rotterdam, The Netherlands"},{"name":"Department of Developmental Biology, Erasmus Medical Centre, 3015 GD Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,28]]},"reference":[{"key":"ref_1","unstructured":"GBD 2021 Adult BMI Collaborators (2025). Global, regional, and national prevalence of adult overweight and obesity, 1990\u20132021, with forecasts to 2050: A forecasting study for the Global Burden of Disease Study 2021. Lancet, 405, 813\u2013838."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"102848","DOI":"10.1016\/j.eclinm.2024.102848","article-title":"Burden of disease attributable to high body mass index: An analysis of data from the Global Burden of Disease Study 2021","volume":"76","author":"Zhou","year":"2024","journal-title":"EClinicalMedicine"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"The GBD 2015 Obesity Collaborators (2017). Health Effects of Overweight and Obesity in 195 Countries over 25 Years. N. Engl. J. Med., 377, 13\u201327.","DOI":"10.1056\/NEJMoa1614362"},{"key":"ref_4","unstructured":"GBD 2021 Gout Collaborators (2024). Global, regional, and national burden of gout, 1990\u20132020, and projections to 2050: A systematic analysis of the Global Burden of Disease Study 2021. Lancet Rheumatol., 6, e507\u2013e517."},{"key":"ref_5","unstructured":"GBD 2021 Rheumatoid Arthritis Collaborators (2023). Global, regional, and national burden of rheumatoid arthritis, 1990-2020, and projections to 2050: A systematic analysis of the Global Burden of Disease Study 2021. Lancet Rheumatol., 5, e594\u2013e610."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1186\/s13075-024-03339-0","article-title":"Epidemiological trends in psoriatic arthritis: A comprehensive population-based study","volume":"26","author":"Haddad","year":"2024","journal-title":"Arthritis Res. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1002\/acr.21660","article-title":"Contribution of obesity to the rise in incidence of rheumatoid arthritis","volume":"65","author":"Crowson","year":"2013","journal-title":"Arthritis Care Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e004227","DOI":"10.1136\/rmdopen-2024-004227","article-title":"Obesity is a risk factor for poor response to treatment in early rheumatoid arthritis: A NORD-STAR study","volume":"10","author":"Dubovyk","year":"2024","journal-title":"RMD Open"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1002\/acr.22932","article-title":"Impact of Obesity on Remission and Disease Activity in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis","volume":"69","author":"Liu","year":"2017","journal-title":"Arthritis Care Res."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Abuhelwa, A.Y., Hopkins, A.M., Sorich, M.J., Proudman, S., Foster, D.J.R., and Wiese, M.D. (2020). Association between obesity and remission in rheumatoid arthritis patients treated with disease-modifying anti-rheumatic drugs. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-75673-7"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.1136\/annrheumdis-2013-205094","article-title":"Overweight decreases the chance of achieving good response and low disease activity in early rheumatoid arthritis","volume":"73","author":"Sandberg","year":"2014","journal-title":"Ann. Rheum. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e70080","DOI":"10.1002\/iid3.70080","article-title":"Obesity and Chronic Inflammation: Implications for Rheumatoid Arthritis, Spondyloarthritis, and Ulcerative Colitis","volume":"13","author":"Corrado","year":"2025","journal-title":"Immun. Inflamm. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/nrrheum.2017.205","article-title":"Targeting lymphatic function as a novel therapeutic intervention for rheumatoid arthritis","volume":"14","author":"Bouta","year":"2018","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1111\/jcmm.13081","article-title":"Endothelial glycocalyx as a critical signalling platform integrating the extracellular haemodynamic forces and chemical signalling","volume":"21","author":"Zeng","year":"2017","journal-title":"J. Cell. Mol. Med."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Rana, M.M., Mohammadi Nouri, P.M., Hosseini, S.H., Roper, B., Withers, S.G., and Kizhakkedathu, J.N. (2025). Reprogramming the glycocalyx: Advances in glycoengineering for immunomodulation and regenerative medicine. Biomaterials, 326.","DOI":"10.1016\/j.biomaterials.2025.123717"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e13922","DOI":"10.1111\/obr.13922","article-title":"Defective lymphatic vasculature in obesity","volume":"26","author":"Zhu","year":"2025","journal-title":"Obes. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.cell.2020.06.039","article-title":"The Lymphatic Vasculature in the 21(st) Century: Novel Functional Roles in Homeostasis and Disease","volume":"182","author":"Oliver","year":"2020","journal-title":"Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/j.devcel.2011.12.020","article-title":"Mechanotransduction, PROX1, and FOXC2 cooperate to control connexin37 and calcineurin during lymphatic-valve formation","volume":"22","author":"Sabine","year":"2012","journal-title":"Dev. Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1038\/s41419-019-2201-1","article-title":"Epigenetic priming by Dot1l in lymphatic endothelial progenitors ensures normal lymphatic development and function","volume":"11","author":"Yoo","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.physbeh.2018.02.044","article-title":"Adipose tissue extrinsic factor: Obesity-induced inflammation and the role of the visceral lymph node","volume":"190","author":"Magnuson","year":"2018","journal-title":"Physiol. Behav."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e12365","DOI":"10.1111\/cpr.12365","article-title":"Diet-induced obesity causes visceral, but not subcutaneous, lymph node hyperplasia via increases in specific immune cell populations","volume":"50","author":"Magnuson","year":"2017","journal-title":"Cell Prolif."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1136\/annrheumdis-2021-222020","article-title":"2021 EULAR recommendations regarding lifestyle behaviours and work participation to prevent progression of rheumatic and musculoskeletal diseases","volume":"82","author":"Gwinnutt","year":"2023","journal-title":"Ann. Rheum. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Schmidt, F.M., Weschenfelder, J., Sander, C., Minkwitz, J., Thormann, J., Chittka, T., Mergl, R., Kirkby, K.C., Fasshauer, M., and Stumvoll, M. (2015). Inflammatory cytokines in general and central obesity and modulating effects of physical activity. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0121971"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1210\/jc.2018-02245","article-title":"Cytokine, Chemokine, and Cytokine Receptor Changes Are Associated With Metabolic Improvements After Bariatric Surgery","volume":"104","author":"Wolf","year":"2019","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2541","DOI":"10.1007\/s10067-025-07426-8","article-title":"Association of regional adiposity distribution with risk of autoimmune diseases","volume":"44","author":"Fan","year":"2025","journal-title":"Clin. Rheumatol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Perera, J., Delrosso, C.A., Nerviani, A., and Pitzalis, C. (2024). Clinical Phenotypes, Serological Biomarkers, and Synovial Features Defining Seropositive and Seronegative Rheumatoid Arthritis: A Literature Review. Cells, 13.","DOI":"10.3390\/cells13090743"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Dong, Y., Greenwood, D.C., Hardie, L.J., and Cade, J.E. (2025). Measures of Adiposity and Risk of Rheumatoid Arthritis in Middle-Aged UK Women: A Prospective Cohort Study. Nutrients, 17.","DOI":"10.3390\/nu17091557"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1159\/000534468","article-title":"The Causal Effect of Obesity on the Risk of 15 Autoimmune Diseases: A Mendelian Randomization Study","volume":"16","author":"Li","year":"2023","journal-title":"Obes. Facts"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1093\/rheumatology\/keab535","article-title":"Long-term weight changes and risk of rheumatoid arthritis among women in a prospective cohort: A marginal structural model approach","volume":"61","author":"Marchand","year":"2022","journal-title":"Rheumatology"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Ohno, T., Aune, D., and Heath, A.K. (2020). Adiposity and the risk of rheumatoid arthritis: A systematic review and meta-analysis of cohort studies. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-71676-6"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e000856","DOI":"10.1136\/rmdopen-2018-000856","article-title":"Interplay between obesity and smoking with regard to RA risk","volume":"5","author":"Hedstrom","year":"2019","journal-title":"RMD Open"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e003785","DOI":"10.1136\/rmdopen-2023-003785","article-title":"When does obesity exert its effect in conferring risk of developing RA: A large study in cohorts of symptomatic persons at risk","volume":"10","author":"Dumoulin","year":"2024","journal-title":"RMD Open"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2863","DOI":"10.1007\/s00296-024-05748-5","article-title":"The association of obesity and the risk of rheumatoid arthritis according to abdominal obesity status: A nationwide population-based study in Korea","volume":"44","author":"Lee","year":"2024","journal-title":"Rheumatol. Int."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1038\/s41584-019-0175-0","article-title":"Preventing psoriatic arthritis: Focusing on patients with psoriasis at increased risk of transition","volume":"15","author":"Scher","year":"2019","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_35","first-page":"721","article-title":"Obesity in early adulthood as a risk factor for psoriatic arthritis","volume":"146","author":"Wong","year":"2010","journal-title":"Arch. Dermatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1136\/annrheumdis-2013-204448","article-title":"Obesity is associated with a lower probability of achieving sustained minimal disease activity state among patients with psoriatic arthritis","volume":"74","author":"Eder","year":"2015","journal-title":"Ann. Rheum. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1136\/annrheumdis-2011-201273","article-title":"Obesity and risk of incident psoriatic arthritis in US women","volume":"71","author":"Li","year":"2012","journal-title":"Ann. Rheum. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1136\/annrheumdis-2012-201299","article-title":"Obesity and the risk of psoriatic arthritis: A population-based study","volume":"71","author":"Love","year":"2012","journal-title":"Ann. Rheum. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1111\/bjd.18227","article-title":"Modifiable risk factors and the development of psoriatic arthritis in people with psoriasis","volume":"182","author":"Green","year":"2020","journal-title":"Br. J. Dermatol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Timsans, J., Palomaki, A., and Kauppi, M. (2024). Gout and Hyperuricemia: A Narrative Review of Their Comorbidities and Clinical Implications. J. Clin. Med., 13.","DOI":"10.3390\/jcm13247616"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Mohseni, M., van der Valk, E.S., Van der Hurk, M.J.B., Savas, M., Boon, M.R., and van Rossum, E.F.C. (2025). Corticosteroid Use and Long-Term Changes in Weight and Waist Circumference: The Lifelines Cohort Study. J. Clin. Endocrinol. Metab., dgaf166.","DOI":"10.1210\/clinem\/dgaf166"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Zou, Y., Li, F., Huang, Q., Zhao, Z., Li, S., and Liu, H. (2025). Associations of weight change patterns with hyperuricemia risk in U.S. adults. Sci. Rep., 15.","DOI":"10.1038\/s41598-025-06276-3"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1186\/s13075-015-0593-6","article-title":"Visceral fat obesity is highly associated with primary gout in a metabolically obese but normal weighted population: A case control study","volume":"17","author":"Lee","year":"2015","journal-title":"Arthritis Res. Ther."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s13098-024-01268-1","article-title":"Relationship between gout, hyperuricemia, and obesity-does central obesity play a significant role?-a study based on the NHANES database","volume":"16","author":"Mao","year":"2024","journal-title":"Diabetol. Metab. Syndr."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1186\/s13075-021-02701-w","article-title":"Association between female reproductive factors and gout: A nationwide population-based cohort study of 1 million postmenopausal women","volume":"23","author":"Eun","year":"2021","journal-title":"Arthritis Res. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1002\/acr.20479","article-title":"Obesity and younger age at gout onset in a community-based cohort","volume":"63","author":"DeMarco","year":"2011","journal-title":"Arthritis Care Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1038\/nrrheum.2015.91","article-title":"Global epidemiology of gout: Prevalence, incidence and risk factors","volume":"11","author":"Kuo","year":"2015","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Eun, Y., Han, K., Lee, S.W., Kim, K., Kang, S., Lee, S., Cha, H.S., Koh, E.M., Kim, H., and Lee, J. (2022). Increased risk of incident gout in young men with metabolic syndrome: A nationwide population-based cohort study of 3.5 million men. Front. Med., 9.","DOI":"10.3389\/fmed.2022.1010391"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s13075-023-03248-8","article-title":"Patients with obesity have more inflamed joints and higher CRP levels during the disease course in ACPA-positive RA but not in ACPA-negative RA","volume":"26","author":"Hollander","year":"2024","journal-title":"Arthritis Res. Ther."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1007\/s10875-010-9507-1","article-title":"Leptin activates human B cells to secrete TNF-alpha, IL-6, and IL-10 via JAK2\/STAT3 and p38MAPK\/ERK1\/2 signaling pathway","volume":"31","author":"Agrawal","year":"2011","journal-title":"J. Clin. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1038\/s41366-023-01344-y","article-title":"Distinct B cell profiles characterise healthy weight and obesity pre- and post-bariatric surgery","volume":"47","author":"Slisere","year":"2023","journal-title":"Int. J. Obes."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1186\/s12979-024-00489-2","article-title":"The role of autoantibodies in bridging obesity, aging, and immunosenescence","volume":"21","author":"Valentino","year":"2024","journal-title":"Immun. Ageing."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e005464","DOI":"10.1136\/rmdopen-2025-005464","article-title":"Influence of body mass index on cardiovascular risk in rheumatoid arthritis varies across anti-citrullinated protein antibody status and biologic use","volume":"11","author":"Karpouzas","year":"2025","journal-title":"RMD Open"},{"key":"ref_54","first-page":"1726","article-title":"Obesity and response to biological therapy in rheumatoid arthritis: The role of body mass index and adipose tissue cytokines","volume":"40","author":"Genre","year":"2022","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1038\/s42255-021-00470-z","article-title":"Metabolic Messengers: Tumour necrosis factor","volume":"3","author":"Sethi","year":"2021","journal-title":"Nat. Metab."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e002103","DOI":"10.1136\/rmdopen-2021-002103","article-title":"Efficacy of tofacitinib in patients with rheumatoid arthritis stratified by baseline body mass index: An analysis of pooled data from phase 3 studies","volume":"8","author":"Dikranian","year":"2022","journal-title":"RMD Open"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e003157","DOI":"10.1136\/rmdopen-2023-003157","article-title":"Association between obesity and likelihood of remission or low disease activity status in psoriatic arthritis applying index-based and patient-based definitions of remission: A cross-sectional study","volume":"9","author":"Leung","year":"2023","journal-title":"RMD Open"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"475","DOI":"10.3899\/jrheum.171034","article-title":"Predictors of Achieving Remission among Patients with Psoriatic Arthritis Initiating a Tumor Necrosis Factor Inhibitor","volume":"46","author":"Ogdie","year":"2019","journal-title":"J. Rheumatol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e42","DOI":"10.1136\/annrheumdis-2020-217251","article-title":"Secukinumab efficacy in patients with PsA is not dependent on patients\u2019 body mass index","volume":"81","author":"Pantano","year":"2022","journal-title":"Ann. Rheum. Dis."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e001486","DOI":"10.1136\/rmdopen-2020-001486","article-title":"Impact of baseline body mass index on the efficacy and safety of tofacitinib in patients with psoriatic arthritis","volume":"7","author":"Giles","year":"2021","journal-title":"RMD Open"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.tem.2017.11.001","article-title":"JAK\/STAT\u2014Emerging Players in Metabolism","volume":"29","author":"Dodington","year":"2018","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3500","DOI":"10.1093\/rheumatology\/keaf076","article-title":"Obesity reduces the urate-lowering efficacy among patients with primary gout: A prospective cohort study","volume":"64","author":"Cheng","year":"2025","journal-title":"Rheumatology"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.smim.2015.10.005","article-title":"Immunological contributions to adipose tissue homeostasis","volume":"27","author":"DiSpirito","year":"2015","journal-title":"Semin. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/nrm2391","article-title":"Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes","volume":"9","author":"Guilherme","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.1172\/JCI200319246","article-title":"Obesity is associated with macrophage accumulation in adipose tissue","volume":"112","author":"Weisberg","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Caer, C., Rouault, C., Le Roy, T., Poitou, C., Aron-Wisnewsky, J., Torcivia, A., Bichet, J.C., Clement, K., Guerre-Millo, M., and Andre, S. (2017). Immune cell-derived cytokines contribute to obesity-related inflammation, fibrogenesis and metabolic deregulation in human adipose tissue. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-02660-w"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"eadl4909","DOI":"10.1084\/jem.20240677","article-title":"Adipose tissue harbors pathogenic T cells in obesity that exacerbate inflammatory arthritis","volume":"222","author":"Faust","year":"2025","journal-title":"J. Exp. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"eadl4909","DOI":"10.1126\/sciimmunol.adl4909","article-title":"Obesity reshapes regulatory T cells in the visceral adipose tissue by disrupting cellular cholesterol homeostasis","volume":"10","author":"Elkins","year":"2025","journal-title":"Sci. Immunol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"5434","DOI":"10.1038\/s41467-024-48935-5","article-title":"Obesity-associated microbiomes instigate visceral adipose tissue inflammation by recruitment of distinct neutrophils","volume":"15","author":"Shantaram","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1189\/jlb.5AB1115-493RR","article-title":"The microenvironment of visceral adipose tissue and liver alter natural killer cell viability and function","volume":"100","author":"Conroy","year":"2016","journal-title":"J. Leukoc. Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.celrep.2019.06.016","article-title":"Innate Lymphoid Cells in the Induction of Obesity","volume":"28","author":"Sasaki","year":"2019","journal-title":"Cell Rep."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1111\/imr.13339","article-title":"Fat-associated lymphoid clusters: Supporting visceral adipose tissue B cell function in immunity and metabolism","volume":"324","author":"Daley","year":"2024","journal-title":"Immunol. Rev."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1838","DOI":"10.1038\/s41366-020-0615-6","article-title":"Obesity-associated T-cell and macrophage activation improve partly after a lifestyle intervention","volume":"44","author":"Wester","year":"2020","journal-title":"Int. J. Obes."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1038\/nature04480","article-title":"Lymphangiogenesis in development and human disease","volume":"438","author":"Alitalo","year":"2005","journal-title":"Nature"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2349","DOI":"10.1084\/jem.20062596","article-title":"Functionally specialized junctions between endothelial cells of lymphatic vessels","volume":"204","author":"Baluk","year":"2007","journal-title":"J. Exp. Med."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Gianesini, S., Rimondi, E., Raffetto, J.D., Melloni, E., Pellati, A., Menegatti, E., Avruscio, G.P., Bassetto, F., Costa, A.L., and Rockson, S. (2023). Human collecting lymphatic glycocalyx identification by electron microscopy and immunohistochemistry. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-30043-x"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"R508","DOI":"10.1152\/ajpregu.00340.2020","article-title":"The glycocalyx: A central regulator of vascular function","volume":"320","author":"Moore","year":"2021","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"den Braanker, H., van Stigt, A.C., Kok, M.R., Lubberts, E., and Bisoendial, R.J. (2021). Single-Cell RNA Sequencing Reveals Heterogeneity and Functional Diversity of Lymphatic Endothelial Cells. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222111976"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/j.celrep.2016.12.078","article-title":"T Cell Migration from Inflamed Skin to Draining Lymph Nodes Requires Intralymphatic Crawling Supported by ICAM-1\/LFA-1 Interactions","volume":"18","author":"Teijeira","year":"2017","journal-title":"Cell Rep."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2979","DOI":"10.1172\/JCI78888","article-title":"GATA2 is required for lymphatic vessel valve development and maintenance","volume":"125","author":"Kazenwadel","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Blum, K.S., Karaman, S., Proulx, S.T., Ochsenbein, A.M., Luciani, P.L., Leroux, J.-C., Wolfrum, C., and Detmar, M. (2014). Chronic high-fat diet impairs collecting lymphatic vessel function in mice. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0094713"},{"key":"ref_82","first-page":"161","article-title":"Regulation of lymphatic function and injury by nitrosative stress in obese mice","volume":"30","author":"Rehal","year":"2020","journal-title":"Mol. Metab."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Weitman, E.S., Aschen, S.Z., Farias-Eisner, G., Albano, N.J., Cuzzone, D.A., Ghanta, S., Zampell, J.C., Thorek, D., and Mehrara, B.J. (2013). Obesity impairs lymphatic fluid transport and dendritic cell migration to lymph nodes. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0070703"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"H165","DOI":"10.1152\/ajpheart.00244.2014","article-title":"Obesity increases inflammation and impairs lymphatic function in a mouse model of lymphedema","volume":"307","author":"Savetsky","year":"2014","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"7073","DOI":"10.1113\/JP273061","article-title":"Obesity-induced lymphatic dysfunction is reversible with weight loss: Involvement of iNOS and perilymphatic inflammation","volume":"594","author":"Nitti","year":"2016","journal-title":"J. Physiol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1038\/ijo.2016.96","article-title":"Obesity but not high-fat diet impairs lymphatic function","volume":"40","author":"Ly","year":"2016","journal-title":"Int. J. Obes."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Savetsky, I.L., Ghanta, S., Gardenier, J.C., Torrisi, J.S., Garcia Nores, G.D., Hespe, G.E., Nitti, M.D., Kataru, R.P., and Mehrara, B.J. (2015). Th2 cytokines inhibit lymphangiogenesis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0126908"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.immuni.2010.12.016","article-title":"T lymphocytes negatively regulate lymph node lymphatic vessel formation","volume":"34","author":"Kataru","year":"2011","journal-title":"Immunity"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s41232-021-00185-4","article-title":"Endothelial-specific depletion of TGF-beta signaling affects lymphatic function","volume":"41","author":"Fukasawa","year":"2021","journal-title":"Inflamm. Regen."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"e240","DOI":"10.1161\/ATVBAHA.120.314935","article-title":"Impairment of Flow-Sensitive Inwardly Rectifying K(+) Channels via Disruption of Glycocalyx Mediates Obesity-Induced Endothelial Dysfunction","volume":"40","author":"Fancher","year":"2020","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Sato, A., Kamekura, R., Kawata, K., Kawada, M., Jitsukawa, S., Yamashita, K., Sato, N., Himi, T., and Ichimiya, S. (2016). Novel Mechanisms of Compromised Lymphatic Endothelial Cell Homeostasis in Obesity: The Role of Leptin in Lymphatic Endothelial Cell Tube Formation and Proliferation. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0158408"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.2353\/ajpath.2009.080963","article-title":"Hypercholesterolemic mice exhibit lymphatic vessel dysfunction and degeneration","volume":"175","author":"Lim","year":"2009","journal-title":"Am. J. Pathol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1038\/ijo.2012.98","article-title":"Reduced adipose tissue lymphatic drainage of macromolecules in obese subjects: A possible link between obesity and local tissue inflammation?","volume":"37","author":"Arngrim","year":"2013","journal-title":"Int. J. Obes."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1097\/PRS.0000000000001271","article-title":"Obesity-induced lymphedema: Clinical and lymphoscintigraphic features","volume":"135","author":"Greene","year":"2015","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/s41366-020-00681-6","article-title":"Lower extremity lymphatic function predicted by body mass index: A lymphoscintigraphic study of obesity and lipedema","volume":"45","author":"Greene","year":"2021","journal-title":"Int. J. Obes."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1038\/s42255-021-00457-w","article-title":"Mesenteric lymphatic dysfunction promotes insulin resistance and represents a potential treatment target in obesity","volume":"3","author":"Cao","year":"2021","journal-title":"Nat. Metab."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.ejpb.2022.10.019","article-title":"Obesity-associated mesenteric lymph leakage impairs the trafficking of lipids, lipophilic drugs and antigens from the intestine to mesenteric lymph nodes","volume":"180","author":"Mikrani","year":"2022","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1038\/ng1642","article-title":"Lymphatic vascular defects promoted by Prox1 haploinsufficiency cause adult-onset obesity","volume":"37","author":"Harvey","year":"2005","journal-title":"Nat. Genet."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1002\/art.42441","article-title":"Targeting Synovial Lymphatic Function as a Novel Therapeutic Intervention for Age-Related Osteoarthritis in Mice","volume":"75","author":"Lin","year":"2023","journal-title":"Arthritis Rheumatol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2666","DOI":"10.1002\/art.24764","article-title":"Inhibition of lymphangiogenesis and lymphatic drainage via vascular endothelial growth factor receptor 3 blockade increases the severity of inflammation in a mouse model of chronic inflammatory arthritis","volume":"60","author":"Guo","year":"2009","journal-title":"Arthritis Rheum."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1002\/art.40047","article-title":"Brief Report: Treatment of Tumor Necrosis Factor-Transgenic Mice With Anti-Tumor Necrosis Factor Restores Lymphatic Contractions, Repairs Lymphatic Vessels, and May Increase Monocyte\/Macrophage Egress","volume":"69","author":"Bouta","year":"2017","journal-title":"Arthritis Rheumatol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1002\/art.41311","article-title":"Altered Lymphatic Vessel Anatomy and Markedly Diminished Lymph Clearance in Affected Hands of Patients With Active Rheumatoid Arthritis","volume":"72","author":"Bell","year":"2020","journal-title":"Arthritis Rheumatol."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Aldrich, M.B., Rasmussen, J.C., Fife, C.E., Shaitelman, S.F., and Sevick-Muraca, E.M. (2020). The Development and Treatment of Lymphatic Dysfunction in Cancer Patients and Survivors. Cancers, 12.","DOI":"10.3390\/cancers12082280"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1002\/art.23505","article-title":"Synovial lymphoid neogenesis does not define a specific clinical rheumatoid arthritis phenotype","volume":"58","author":"Thurlings","year":"2008","journal-title":"Arthritis Rheum."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2795","DOI":"10.1016\/j.immuni.2021.10.003","article-title":"Ileitis-associated tertiary lymphoid organs arise at lymphatic valves and impede mesenteric lymph flow in response to tumor necrosis factor","volume":"54","author":"Czepielewski","year":"2021","journal-title":"Immunity"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"e20241799","DOI":"10.1084\/jem.20241799","article-title":"S1PR1 regulates lymphatic valve development and tertiary lymphoid organ formation in the ileum","volume":"222","author":"Geng","year":"2025","journal-title":"J. Exp. Med."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"G624","DOI":"10.1152\/ajpgi.00334.2024","article-title":"The spatiotemporal development of mesenteric lymphatic changes in the TNF(DeltaARE\/+) mouse model of terminal ileitis","volume":"328","author":"Keane","year":"2025","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/s41392-024-01931-z","article-title":"Glucagon-like peptide-1 receptor: Mechanisms and advances in therapy","volume":"9","author":"Zheng","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"103864","DOI":"10.1016\/j.autrev.2025.103864","article-title":"Glucagon-Like Peptide-1 (GLP-1) receptor agonists in rheumatology: A review of current evidence and future directions","volume":"24","author":"Bilgin","year":"2025","journal-title":"Autoimmun. Rev."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1038\/s41419-017-0217-y","article-title":"Glucagon-like peptide-1 receptor regulates endoplasmic reticulum stress-induced apoptosis and the associated inflammatory response in chondrocytes and the progression of osteoarthritis in rat","volume":"9","author":"Chen","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s12950-019-0218-y","article-title":"The GLP-1 agonist, liraglutide, ameliorates inflammation through the activation of the PKA\/CREB pathway in a rat model of knee osteoarthritis","volume":"16","author":"Que","year":"2019","journal-title":"J. Inflamm."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Brown, S., Tadros, A.B., Montagna, G., Bell, T., Crowley, F., Gallagher, E.J., and Dayan, J.H. (2024). Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may reduce the risk of developing cancer-related lymphedema following axillary lymph node dissection (ALND). Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1457363"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/21\/7641\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T10:03:41Z","timestamp":1761732221000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/21\/7641"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,28]]},"references-count":112,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["jcm14217641"],"URL":"https:\/\/doi.org\/10.3390\/jcm14217641","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,28]]}}}