{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:57:57Z","timestamp":1791223077659,"version":"4.1.0"},"reference-count":34,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002850","name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["11241108"],"award-info":[{"award-number":["11241108"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background and aims<\/jats:title>\n                    <jats:p>\n                      Adiponectin circulates as multimers with potentially distinct biological roles, yet most human studies report total adiponectin, which may mask multimer-specific metabolic information\n                      <jats:bold>.<\/jats:bold>\n                      This study aimed to determine whether circulating low- (LMW) and medium-molecular-weight (MMW) adiponectin and their relative pattern are associated with cardiometabolic, behavioral, and chrononutrition characteristics in adults undergoing screening for the RIO Study.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>In this cross-sectional study, 112 adults who completed the screening assessment for the RIO Study underwent anthropometric\/body-composition assessment, fasting biochemistry, self-reported physical activity and sitting time, and chrononutrition evaluation. Serum adiponectin multimers were quantified by Western immunoblotting; under the present experimental conditions, only low-molecular-weight (LMW) and medium-molecular-weight (MMW) multimers were consistently detectable. Associations were assessed using Pearson correlations, adjusted multiple linear regression, and principal component analysis (PCA). Exploratory correlations suggested associations of MMW adiponectin and the MMW\/LMW ratio with several anthropometric and metabolic variables. However, after multivariable adjustment, most associations with adiposity and lipid variables were attenuated, whereas inverse associations with GGT and ALT persisted. MMW adiponectin remained inversely associated with GGT (\u03b2=\u22120.37, p\u2009&lt;\u20090.001) and ALT (\u03b2=\u22120.32, p\u2009=\u20090.002). Physically active participants had higher MMW adiponectin and MMW\/LMW ratios than inactive participants (FDR-adjusted p\u2009&lt;\u20090.05). Exploratory PCA identified five components with eigenvalues &gt;1, together explaining 66.6% of the total variance. LMW and MMW adiponectin contributed to the multivariate structure, including a shared adiponectin-related component.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In this cardiometabolic screening cohort, MMW adiponectin and the MMW\/LMW ratio showed persistent inverse associations with selected liver-enzyme measures, particularly GGT and ALT, after adjustment for potential confounders. These exploratory findings support further investigation of LMW and MMW adiponectin as metabolic biomarkers using longitudinal and interventional designs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0360041","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:37:46Z","timestamp":1791221866000},"page":"e0360041","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Circulating low- and medium-molecular-weight adiponectin are associated with metabolic phenotypes in adults undergoing cardiometabolic screening"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6336-5571","authenticated-orcid":true,"given":"Sergio","family":"Mart\u00ednez-Huenchull\u00e1n","sequence":"first","affiliation":[{"name":"Universidad San Sebasti\u00e1n","place":["Valdivia, Chile"],"department":["Carrera de Kinesiolog\u00eda, Facultad de Ciencias de la Rehabilitaci\u00f3n y Calidad de Vida"]},{"name":"Universidad San Sebasti\u00e1n","place":["Santiago, Chile"],"department":["Centro de Biolog\u00eda Celular y Biomedicina (CEBICEM), Facultad de Ciencias"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Cares","sequence":"additional","affiliation":[{"name":"Universidad San Sebasti\u00e1n","place":["Valdivia, Chile"],"department":["Carrera de Tecnolog\u00eda M\u00e9dica, Facultad de Ciencias"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josefina","family":"Enr\u00edquez","sequence":"additional","affiliation":[{"name":"Universidad San Sebasti\u00e1n","place":["Valdivia, Chile"],"department":["Carrera de Nutrici\u00f3n y Diet\u00e9tica, Facultad de Ciencias de la Rehabilitaci\u00f3n y Calidad de Vida"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Consuelo","family":"Quezada","sequence":"additional","affiliation":[{"name":"Universidad San Sebasti\u00e1n","place":["Valdivia, Chile"],"department":["Carrera de Nutrici\u00f3n y Diet\u00e9tica, Facultad de Ciencias de la Rehabilitaci\u00f3n y Calidad de Vida"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Molina","sequence":"additional","affiliation":[{"name":"Universidad San Sebasti\u00e1n","place":["Valdivia, Chile"],"department":["Carrera de Nutrici\u00f3n y Diet\u00e9tica, Facultad de Ciencias de la Rehabilitaci\u00f3n y Calidad de Vida"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Ross","sequence":"additional","affiliation":[{"name":"Instituto de Ciencias de la Educaci\u00f3n, Universidad Austral de Chile","place":["Valdivia, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Bentes","sequence":"additional","affiliation":[{"name":"Instituto de Anatom\u00eda, Patolog\u00eda e Histolog\u00eda, Universidad Austral de Chile","place":["Valdivia, Chile"],"department":["Facultad de Medicina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanara","family":"Pavez","sequence":"additional","affiliation":[{"name":"Doctorado en Enfermedades Cr\u00f3nicas, Facultad de Ciencias, Universidad San Sebasti\u00e1n","place":["Santiago, Chile"]},{"name":"Universidad Central de Chile, Carrera de Tecnolog\u00eda M\u00e9dica","place":["Santiago, Chile"],"department":["Facultad de Medicina y Ciencias de la Salud"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Rubilar","sequence":"additional","affiliation":[{"name":"Universidad San Sebasti\u00e1n","place":["Valdivia, Chile"],"department":["Carrera de Tecnolog\u00eda M\u00e9dica, Facultad de Ciencias"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catalina","family":"Ram\u00edrez-Contreras","sequence":"additional","affiliation":[{"name":"Universidad del B\u00edo-B\u00edo","place":["Chill\u00e1n, Chile"],"department":["Departamento de Nutrici\u00f3n y Salud P\u00fablica, Facultad de Ciencias de la Salud y los Alimentos"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monserrat","family":"Fit\u00f3","sequence":"additional","affiliation":[{"name":"Hospital del Mar Research Institute (HMRIB)","place":["Barcelona, Spain"]},{"name":"CIBER de Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n (CIBEROBN), Instituto de Salud Carlos III","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8593-1477","authenticated-orcid":true,"given":"\u00c1lvaro","family":"Hern\u00e1ez","sequence":"additional","affiliation":[{"name":"Hospital del Mar Research Institute (HMRIB)","place":["Barcelona, Spain"]},{"name":"Universitat Ramon Llull, Blanquerna School of Health Sciences","place":["Barcelona, Spain"]},{"name":"CIBER de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6874-4434","authenticated-orcid":true,"given":"Viviana","family":"Sandoval","sequence":"additional","affiliation":[{"name":"Universidad San Sebasti\u00e1n","place":["Valdivia, Chile"],"department":["Carrera de Nutrici\u00f3n y Diet\u00e9tica, Facultad de Ciencias de la Rehabilitaci\u00f3n y Calidad de Vida"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"pone.0360041.ref001","doi-asserted-by":"crossref","first-page":"156320","DOI":"10.1016\/j.metabol.2025.156320","article-title":"Sedentary behaviour and cardiometabolic health: Integrating the potential underlying molecular health aspects","volume":"170","author":"WMA Franssen","year":"2025","journal-title":"Metabolism"},{"issue":"2","key":"pone.0360041.ref002","doi-asserted-by":"crossref","first-page":"359","DOI":"10.3390\/biomedicines13020359","article-title":"Decoding health: Exploring essential biomarkers linked to metabolic dysfunction-associated steatohepatitis and type 2 diabetes mellitus","volume":"13","author":"S Mukherjee","year":"2025","journal-title":"Biomedicines"},{"key":"pone.0360041.ref003","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.3389\/fphys.2018.01238","article-title":"Meta-analysis of adiponectin as a biomarker for the detection of metabolic syndrome","volume":"9","author":"Z Liu","year":"2018","journal-title":"Front Physiol"},{"issue":"1","key":"pone.0360041.ref004","doi-asserted-by":"crossref","first-page":"5598","DOI":"10.1038\/s41598-020-62465-2","article-title":"High serum adiponectin as a biomarker of renal dysfunction: Results from the KNOW-CKD study","volume":"10","author":"SH Song","year":"2020","journal-title":"Sci Rep"},{"issue":"4","key":"pone.0360041.ref005","doi-asserted-by":"crossref","first-page":"29","DOI":"10.3390\/reprodmed6040029","article-title":"Adiponectin as a biomarker of preeclampsia: A systematic review","volume":"6","author":"I Carrilho","year":"2025","journal-title":"Reprod Med"},{"issue":"4","key":"pone.0360041.ref006","doi-asserted-by":"crossref","DOI":"10.1111\/jne.13493","article-title":"Plasma adiponectin and biomarker-confirmed Alzheimer\u2019s disease in a tertiary memory clinic","volume":"37","author":"L Sindzingre","year":"2025","journal-title":"J Neuroendocrinol"},{"issue":"2","key":"pone.0360041.ref007","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1007\/s12020-013-9890-5","article-title":"Adiponectin as predictor for diabetes among pre-diabetic groups","volume":"44","author":"H-S Kim","year":"2013","journal-title":"Endocrine"},{"issue":"11","key":"pone.0360041.ref008","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.3390\/metabo12111086","article-title":"Association of serum adiponectin biomarker with metabolic syndrome components in koreans with extremely high HDL cholesterol levels in general health checkup","volume":"12","author":"HS Yang","year":"2022","journal-title":"Metabolites"},{"key":"pone.0360041.ref009","article-title":"Adiponectin\/resistin evaluation is a gold biomarker for monitoring CVD in patients with metabolic syndrome","volume":"160","author":"M Abdelmonem","year":"2023","journal-title":"American Journal of Clinical Pathology"},{"issue":"2","key":"pone.0360041.ref010","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s11154-013-9256-6","article-title":"Assembly of adiponectin oligomers","volume":"15","author":"T-S Tsao","year":"2014","journal-title":"Rev Endocr Metab Disord"},{"key":"pone.0360041.ref011","doi-asserted-by":"crossref","first-page":"651732","DOI":"10.3389\/fphys.2021.651732","article-title":"Adiponectin and the control of metabolic dysfunction: Is exercise the magic bullet?","volume":"12","author":"LI Otu","year":"2021","journal-title":"Front Physiol"},{"issue":"3","key":"pone.0360041.ref012","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1042\/BJ20071492","article-title":"Post-translational modifications of adiponectin: Mechanisms and functional implications","volume":"409","author":"Y Wang","year":"2008","journal-title":"Biochem J"},{"key":"pone.0360041.ref013","doi-asserted-by":"crossref","first-page":"154008","DOI":"10.1016\/j.metabol.2019.154008","article-title":"Skeletal muscle adiponectin induction in obesity and exercise","volume":"102","author":"SF Martinez-Huenchullan","year":"2020","journal-title":"Metabolism"},{"key":"pone.0360041.ref014","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/bs.acc.2018.02.007","article-title":"Adiponectin and its isoforms in pathophysiology","volume":"85","author":"M van Andel","year":"2018","journal-title":"Adv Clin Chem"},{"issue":"20","key":"pone.0360041.ref015","doi-asserted-by":"crossref","DOI":"10.14814\/phy2.13848","article-title":"Skeletal muscle adiponectin induction depends on diet, muscle type\/activity, and exercise modality in C57BL\/6 mice","volume":"6","author":"SF Martinez-Huenchullan","year":"2018","journal-title":"Physiol Rep"},{"issue":"1","key":"pone.0360041.ref016","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1080\/13813455.2020.1797098","article-title":"Constant-moderate versus high-intensity interval training on heart adiponectin levels in high-fat fed mice: A preventive and treatment approach","volume":"129","author":"SF Mart\u00ednez-Huenchull\u00e1n","year":"2023","journal-title":"Arch Physiol Biochem"},{"issue":"21","key":"pone.0360041.ref017","doi-asserted-by":"crossref","first-page":"3397","DOI":"10.3390\/nu17213397","article-title":"Study Protocol and Baseline Cardiometabolic Characterization of the RIO-Study (Response to an Intervention with Omega-3): A Randomized, Double-Blind, Placebo-Controlled Crossover Trial on Lipid and Inflammatory Profiles in Overweight and Obese Adults with Hypertriglyceridemia in Valdivia, Chile","volume":"17","author":"J Enr\u00edquez","year":"2025","journal-title":"Nutrients"},{"issue":"4","key":"pone.0360041.ref018","doi-asserted-by":"crossref","first-page":"159","DOI":"10.4103\/2229-3485.140555","article-title":"Basics of case report form designing in clinical research","volume":"5","author":"S Bellary","year":"2014","journal-title":"Perspect Clin Res"},{"issue":"10","key":"pone.0360041.ref019","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0291604","article-title":"Validity and reliability of the international physical activity questionnaire short form in Chilean adults","volume":"18","author":"T Balboa-Castillo","year":"2023","journal-title":"PLoS One"},{"issue":"1","key":"pone.0360041.ref020","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1186\/s13102-025-01433-7","article-title":"Acute effects of high-intensity interval training on adiponectin isoforms in inactive young adults: A quasi-experimental study","volume":"17","author":"D Alvarado-Carrasco","year":"2025","journal-title":"BMC Sports Sci Med Rehabil"},{"issue":"1","key":"pone.0360041.ref021","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1161\/01.ATV.0000099786.99623.EF","article-title":"Adiponectin and metabolic syndrome","volume":"24","author":"Y Matsuzawa","year":"2004","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"1","key":"pone.0360041.ref022","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1161\/CIRCRESAHA.120.314458","article-title":"Adiponectin, leptin and cardiovascular disorders","volume":"128","author":"S Zhao","year":"2021","journal-title":"Circ Res"},{"issue":"1","key":"pone.0360041.ref023","doi-asserted-by":"crossref","first-page":"249","DOI":"10.2337\/diabetes.55.01.06.db05-1105","article-title":"Adiponectin multimeric complexes and the metabolic syndrome trait cluster","volume":"55","author":"C Lara-Castro","year":"2006","journal-title":"Diabetes"},{"issue":"3","key":"pone.0360041.ref024","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0192609","article-title":"Ratio of low molecular weight serum adiponectin to the total adiponectin value is associated with type 2 diabetes through its relation to increasing insulin resistance","volume":"13","author":"M Iwata","year":"2018","journal-title":"PLoS One"},{"issue":"4","key":"pone.0360041.ref025","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.3390\/ijms21041219","article-title":"Multifaceted physiological roles of adiponectin in inflammation and diseases","volume":"21","author":"HM Choi","year":"2020","journal-title":"Int J Mol Sci"},{"issue":"1","key":"pone.0360041.ref026","article-title":"Enhanced adiponectin multimer ratio and skeletal muscle adiponectin receptor expression following exercise training and diet in older insulin-resistant adults","volume":"293","author":"VB O\u2019Leary","year":"2007","journal-title":"Am J Physiol Endocrinol Metab"},{"issue":"1","key":"pone.0360041.ref027","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.beem.2013.06.003","article-title":"Regulation of adiponectin multimerization, signaling and function","volume":"28","author":"M Liu","year":"2014","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"pone.0360041.ref028","doi-asserted-by":"crossref","DOI":"10.1136\/ard.2010.149104.12","article-title":"Adiponectin isoforms differentially affect gene expression of rheumatoid arthritis synovial fibroblasts","volume":"70","author":"K Frommer","year":"2011","journal-title":"Annals of the Rheumatic Diseases"},{"key":"pone.0360041.ref029","doi-asserted-by":"crossref","first-page":"459","DOI":"10.3389\/fphys.2019.00459","article-title":"Constant-moderate and high-intensity interval training have differential benefits on insulin sensitive tissues in high-fat fed mice","volume":"10","author":"SF Martinez-Huenchullan","year":"2019","journal-title":"Front Physiol"},{"issue":"11","key":"pone.0360041.ref030","doi-asserted-by":"crossref","first-page":"3273","DOI":"10.3390\/jcm13113273","article-title":"Moderate-intensity constant and high-intensity interval training confer differential metabolic benefits in skeletal muscle, white adipose tissue, and liver of candidates to undergo bariatric surgery","volume":"13","author":"M Ru\u00edz-Uribe","year":"2024","journal-title":"J Clin Med"},{"issue":"2","key":"pone.0360041.ref031","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/pr.2014.73","article-title":"Adiponectin and markers of metabolic syndrome in obese children and adolescents: impact of 8-mo regular physical exercise program","volume":"76","author":"H Nascimento","year":"2014","journal-title":"Pediatr Res"},{"issue":"1","key":"pone.0360041.ref032","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1186\/s12967-016-1044-0","article-title":"Effects of eight weeks of time-restricted feeding (16\/8) on basal metabolism, maximal strength, body composition, inflammation, and cardiovascular risk factors in resistance-trained males","volume":"14","author":"T Moro","year":"2016","journal-title":"J Transl Med"},{"issue":"2","key":"pone.0360041.ref033","doi-asserted-by":"crossref","DOI":"10.1016\/j.diabres.2010.08.008","article-title":"Sex-differences in adiponectin levels and body fat distribution: Longitudinal observations in Afro-Jamaicans","volume":"90","author":"MS Boyne","year":"2010","journal-title":"Diabetes Res Clin Pract"},{"issue":"4","key":"pone.0360041.ref034","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.trsl.2014.04.008","article-title":"Adiposity distribution influences circulating adiponectin levels","volume":"164","author":"M Guenther","year":"2014","journal-title":"Transl Res"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0360041","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:37:57Z","timestamp":1791221877000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0360041"}},"subtitle":[],"editor":[{"given":"Etsuro","family":"Ito","sequence":"first","affiliation":[{"name":"Waseda University: Waseda Daigaku","place":["JAPAN"]}],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,10,5]]},"references-count":34,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,10,5]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0360041","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,5]]}}}