{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T18:31:16Z","timestamp":1789497076220,"version":"build-2803163510"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,12,25]],"date-time":"2023-12-25T00:00:00Z","timestamp":1703462400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2009600"],"award-info":[{"award-number":["2022YFC2009600"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2024,2]]},"abstract":"Abstract<\/jats:title>Background<\/jats:title>The obesity paradigm has been a health concern globally for many years, its meaning is controversial. In this study, we assess the characteristics and causes of obesity paradigm and detail the mediation of obesity and inflammation on survival.<\/jats:p><\/jats:sec>Methods<\/jats:title>The original cohort included participants from the US National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018, a prospective cohort of a nationally representative sample of adult participants; the oncology validation cohort included patients from the Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) from 2013 to 2021, a prospective cohort of Chinese patients with cancer. Survival analysis was performed using weighted (NHANES) or unweighted (INSCOC) Cox survival analyses. The normal BMI group was used as a reference for all comparisons. Systemic inflammation was defined as neutrophil\u2010to\u2010lymphocyte ratio (NLR)\u00a0>\u00a03. Model\u2010based causal mediation analysis was used to identify the mediators.<\/jats:p><\/jats:sec>Results<\/jats:title>A total of 52\u00a0270 (weighted population: 528506229) participants of the NHANES [mean follow\u2010up times: 10.2\u00a0years; mean age (SD): 47 (19.16) years] were included in the original cohort; and a total of 17\u00a0418 patients with cancer of INSCOC [mean follow\u2010up times: 2.9\u00a0years; mean age (SD): 57.37 (11.66) years] were included in the validation cohort. In the subgroups of all the participants, the obesity paradigm was more apparent in older participants and participants with disease [HR (95% CI): age\u00a0\u2265\u00a065\u00a0years, 0.84 (0.76, 0.93); with cancer, 0.84 (0.71, 0.99); with CVD, 0.74 (0.65, 0.85)]. As aged, the protective effect of a high BMI on survival gradually increased and a high BMI showed the effect of a protective factor on older participants [for obese II, HR (95% CI): young adults, 1.91 (1.40, 2.62); middle age, 1.56 (1.28, 1.91); old adults, 0.85 (0.76, 0.96]). The aged\u2010related obesity paradigm in patients with cancer from the NHANES was verified in the INSCOC cohorts [for obese, HR (95%CI): 0.65 (0.52, 0.81)]. The NLR is an important mediator of the effect of BMI on survival (proportion of mediation\u00a0=\u00a015.4%).<\/jats:p><\/jats:sec>Conclusions<\/jats:title>The obesity paradigm has a strong correlation with age. Relative to normal weight, obese in young people was association with higher all\u2010cause mortality, and obese in elderly people was not association with higher mortality. The protection of obesity is association with systemic inflammation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13415","type":"journal-article","created":{"date-parts":[[2023,12,26]],"date-time":"2023-12-26T07:04:32Z","timestamp":1703574272000},"page":"442-452","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["The age\u2010related obesity paradigm: results from two large prospective cohort studies"],"prefix":"10.1002","volume":"15","author":[{"given":"Yi\u2010Zhong","family":"Ge","sequence":"first","affiliation":[{"name":"Department of Gastrointestinal Surgery, Department of Clinical Nutrition, Beijing Shijitan Hospital Capital Medical University Beijing China"},{"name":"The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University Wenzhou China"},{"name":"National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital Capital Medical University Beijing China"},{"name":"Key Laboratory of Cancer FSMP for State Market Regulation Beijing China"},{"name":"Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery, Department of Clinical Nutrition, Beijing Shijitan Hospital Capital Medical University Beijing China"},{"name":"National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital Capital Medical University Beijing China"},{"name":"Key Laboratory of Cancer FSMP for State Market Regulation Beijing China"},{"name":"Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery, Department of Clinical Nutrition, Beijing Shijitan Hospital Capital Medical University Beijing China"},{"name":"National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital Capital Medical University Beijing China"},{"name":"Key Laboratory of Cancer FSMP for State Market Regulation Beijing China"},{"name":"Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery, Department of Clinical Nutrition, Beijing Shijitan Hospital Capital Medical University Beijing China"},{"name":"National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital Capital Medical University Beijing China"},{"name":"Key Laboratory of Cancer FSMP for State Market Regulation Beijing China"},{"name":"Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition Beijing China"},{"name":"Department of Colorectal Surgery, Cancer Hospital of University of Chinese Academy of Sciences Zhejiang Cancer Hospital Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen\u2010An","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery, Department of Clinical Nutrition, Beijing Shijitan Hospital Capital Medical University Beijing China"},{"name":"National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital Capital Medical University Beijing China"},{"name":"Key Laboratory of Cancer FSMP for State Market Regulation Beijing China"},{"name":"Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo\u2010Tian","family":"Ruan","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery, Department of Clinical Nutrition, Beijing Shijitan Hospital Capital Medical University Beijing China"},{"name":"National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital Capital Medical University Beijing China"},{"name":"Key Laboratory of Cancer FSMP for State Market Regulation Beijing China"},{"name":"Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai\u2010Lun","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery, Department of Clinical Nutrition, Beijing Shijitan Hospital Capital Medical University Beijing China"},{"name":"National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital Capital Medical University Beijing China"},{"name":"Key Laboratory of Cancer FSMP for State Market Regulation Beijing China"},{"name":"Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng\u2010Meng","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery, Department of Clinical Nutrition, Beijing Shijitan Hospital Capital Medical University Beijing China"},{"name":"National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital Capital Medical University Beijing China"},{"name":"Key Laboratory of Cancer FSMP for State Market Regulation Beijing China"},{"name":"Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi\u2010Qi","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery, Department of Clinical Nutrition, Beijing Shijitan Hospital Capital Medical University Beijing China"},{"name":"National Clinical Research Center for Geriatric Diseases, Xuanwu 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