{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T22:54:38Z","timestamp":1793314478366,"version":"4.5.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"16","license":[{"start":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T00:00:00Z","timestamp":1749081600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["209933838"],"award-info":[{"award-number":["209933838"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Collaborative Research CenterCentre"},{"DOI":"10.13039\/501100005385","name":"Council for Higher Education","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005385","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>We explored the manifestations of individual weight loss (WL) response to long-term lifestyle interventions on cardiometabolic risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>We pooled data from three large long-term lifestyle WL-intervention trials: 24-month DIRECT (ClinicalTrials.gov: NCT00160108; n = 322; 87% adherence), 18-month CENTRAL (ClinicalTrials.gov: NCT01530724; n = 278; 86% adherence), and 18-month DIRECT PLUS (ClinicalTrials.gov: NCT03020186; n = 294; 89% adherence). We analyzed longitudinal changes in cardiometabolic risk markers, including anthropometrics, blood biomarkers, and magnetic-resonance-imaging-assessed fat depots, and measured DNA-methylation, proteomics, and metabolomics. Among trial completers (n = 761, mean age = 50.4 years; 89% men, baseline body-mass-index = 30.1\u2005kg\/m2), mean WL was \u22123.3\u2005kg (\u22123.5%). We classified participants as Successful-WL (36%) with relative-WL &amp;gt; 5%, WL-Resistant (28%) who did not lose or gained weight, and Moderate-WL (36%) with WL between 0% and 5%. Successful-WL achieved the greatest improvements in multiple health indicators. However, the WL-Resistant also showed some significant improvements, with increased high-density-lipoprotein-cholesterol (HDLc) and decreased leptin and visceral fat (P &amp;lt; 0.05 vs. baseline). Overall, each 1\u2005kg sustained lifestyle-induced WL was associated with improvements in lipid markers and insulin resistance [HDLc (+1.44%), triglycerides (\u22121.37%), insulin (\u22122.46%), HOMA-IR (\u22122.71%), leptin (\u22122.79%)] and intrahepatic-fat regression (\u22120.49 absolute-units)] and modest but significant change in systolic and diastolic blood pressures (\u22120.26% and \u22120.36%). We identified 12 significant methylation sites that are associated with Successful-WL (FDR &amp;lt; 0.05; AUC = 0.73).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>While only \u223cone-third of individuals achieved long-term WL, the Moderate-WL and WL-Resistant individuals could benefit improvements in visceral adiposity and cardiometabolic risk by shifting towards a healthy lifestyle pattern, beyond WL. Site-specific DNA methylation may predict an individual's likelihood of successful WL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Registration<\/jats:title>\n                    <jats:p>NCT00160108, NCT01530724, NCT03020186.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/eurjpc\/zwaf308","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T09:16:44Z","timestamp":1747819004000},"page":"1660-1670","source":"Crossref","is-referenced-by-count":11,"title":["Individual response to lifestyle interventions: a pooled analysis of three long-term weight loss trials"],"prefix":"10.1093","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2480-3751","authenticated-orcid":false,"given":"Anat","family":"Yaskolka Meir","sequence":"first","affiliation":[{"name":", Faculty of Health Sciences, Ben-Gurion University of the Negev The International Center of Health Innovation & Nutrition in memory of Manya Igel , P.O. Box 653, Beer-Sheva 8410501 ,","place":["Israel"]},{"name":"Department of Epidemiology, Harvard T.H. Chan School of Public Health , Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4234-6504","authenticated-orcid":false,"given":"Gal","family":"Tsaban","sequence":"additional","affiliation":[{"name":", Faculty of Health Sciences, Ben-Gurion University of the Negev The International Center of Health Innovation & Nutrition in memory of Manya Igel , P.O. Box 653, Beer-Sheva 8410501 ,","place":["Israel"]},{"name":"Department of Cardiovascular Medicine, Mayo Clinic , Rochester, MN 55905 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3028-5492","authenticated-orcid":false,"given":"Ehud","family":"Rinott","sequence":"additional","affiliation":[{"name":", Faculty of Health Sciences, Ben-Gurion University of the Negev The International Center of Health Innovation & Nutrition in memory of Manya Igel , P.O. Box 653, Beer-Sheva 8410501 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hila","family":"Zelicha","sequence":"additional","affiliation":[{"name":", Faculty of Health Sciences, Ben-Gurion University of the Negev The International Center of Health Innovation & Nutrition in memory of Manya Igel , P.O. Box 653, Beer-Sheva 8410501 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Schwarzfuchs","sequence":"additional","affiliation":[{"name":"Soroka University Medical Center , Beer-Sheva 8410501 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yftach","family":"Gepner","sequence":"additional","affiliation":[{"name":", Faculty of Health Sciences, Ben-Gurion University of the Negev The International Center of Health Innovation & Nutrition in memory of Manya Igel , P.O. Box 653, Beer-Sheva 8410501 ,","place":["Israel"]},{"name":"Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, and Sylvan Adams Sports Institute, Tel-Aviv University , Tel-Aviv 6997801 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Assaf","family":"Rudich","sequence":"additional","affiliation":[{"name":", Faculty of Health Sciences, Ben-Gurion University of the Negev The International Center of Health Innovation & Nutrition in memory of Manya Igel , P.O. Box 653, Beer-Sheva 8410501 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8398-6455","authenticated-orcid":false,"given":"Ilan","family":"Shelef","sequence":"additional","affiliation":[{"name":"Soroka University Medical Center , Beer-Sheva 8410501 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Bl\u00fcher","sequence":"additional","affiliation":[{"name":"Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Center Munich at the University of Leipzig and University Hospital Leipzig , Leipzig 04103 ,","place":["Germany"]},{"name":"Medical Department III\u2014Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center , Liebigstra\u00dfe 20, Leipzig 04103 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Stumvoll","sequence":"additional","affiliation":[{"name":"Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Center Munich at the University of Leipzig and University Hospital Leipzig , Leipzig 04103 ,","place":["Germany"]},{"name":"Medical Department III\u2014Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center , Liebigstra\u00dfe 20, Leipzig 04103 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4034-5535","authenticated-orcid":false,"given":"Uta","family":"Ceglarek","sequence":"additional","affiliation":[{"name":"Institute of Laboratory Medicine, Clinical Chemistry, and Molecular Diagnostics, University of Leipzig Medical Center , Leipzig 04103 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0714-6160","authenticated-orcid":false,"given":"Berend","family":"Isermann","sequence":"additional","affiliation":[{"name":"Institute of Laboratory Medicine, Clinical Chemistry, and Molecular Diagnostics, University of Leipzig Medical Center , Leipzig 04103 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora","family":"Kl\u00f6ting","sequence":"additional","affiliation":[{"name":"Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Center Munich at the University of Leipzig and University Hospital Leipzig , Leipzig 04103 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Keller","sequence":"additional","affiliation":[{"name":"Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Center Munich at the University of Leipzig and University Hospital Leipzig , Leipzig 04103 ,","place":["Germany"]},{"name":"Medical Department III\u2014Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center , Liebigstra\u00dfe 20, Leipzig 04103 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0290-5423","authenticated-orcid":false,"given":"Peter","family":"Kovacs","sequence":"additional","affiliation":[{"name":"Medical Department III\u2014Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center , Liebigstra\u00dfe 20, Leipzig 04103 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8041-7791","authenticated-orcid":false,"given":"Lu","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University , New Orleans, LA 70118 ,","place":["USA"]},{"name":"Department of Nutrition, Harvard T.H. Chan School of Public Health , 655 Huntington Ave, Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong D","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Harvard T.H. Chan School of Public Health , 655 Huntington Ave, Boston, MA 02115 ,","place":["USA"]},{"name":"Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School , Boston, MA 02115 ,","place":["USA"]},{"name":"Broad Institute of MIT and Harvard , Cambridge, MA 02142 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liming","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Harvard T.H. Chan School of Public Health , Boston, MA 02115 ,","place":["USA"]},{"name":"Department of Biostatistics, Harvard T.H. Chan School of Public Health , Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank B","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Harvard T.H. Chan School of Public Health , Boston, MA 02115 ,","place":["USA"]},{"name":"Department of Nutrition, Harvard T.H. Chan School of Public Health , 655 Huntington Ave, Boston, MA 02115 ,","place":["USA"]},{"name":"Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School , Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meir J","family":"Stampfer","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Harvard T.H. Chan School of Public Health , Boston, MA 02115 ,","place":["USA"]},{"name":"Department of Nutrition, Harvard T.H. Chan School of Public Health , 655 Huntington Ave, Boston, MA 02115 ,","place":["USA"]},{"name":"Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School , Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9050-4605","authenticated-orcid":false,"given":"Iris","family":"Shai","sequence":"additional","affiliation":[{"name":", Faculty of Health Sciences, Ben-Gurion University of the Negev The International Center of Health Innovation & Nutrition in memory of Manya Igel , P.O. Box 653, Beer-Sheva 8410501 ,","place":["Israel"]},{"name":"Medical Department III\u2014Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center , Liebigstra\u00dfe 20, Leipzig 04103 ,","place":["Germany"]},{"name":"Department of Nutrition, Harvard T.H. 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