Alvaro Obeso, Gabin Drouard, Teemu Palviainen, Xiaoling Wang, Miina Ollikainen, Karri Silventoinen, Jaakko Kaprio
{"title":"蛋白质组学与BMI波动和长期变化的关联：一项40年的随访研究。","authors":"Alvaro Obeso, Gabin Drouard, Teemu Palviainen, Xiaoling Wang, Miina Ollikainen, Karri Silventoinen, Jaakko Kaprio","doi":"10.1111/dom.16448","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>While some studies have explored associations between weight change and blood proteins, most have been intervention-based, offering limited insight into proteomic associations with long-term weight gain. It remains unclear whether plasma proteins are related to BMI fluctuation over time. This study investigates associations of long-term BMI changes and fluctuations with over 1000 plasma proteins involved in cardiometabolic and inflammation functions.</p><p><strong>Data and methods: </strong>The study included 304 Finnish adult twins (117 men) born before 1958 from the Older Finnish Twin Cohort, with BMI data spanning five time points (1975, 1981, 1990, 2011 and 2012-2014). Proteomic data were derived from blood samples collected at the last BMI measurement. Linear mixed-effects models analysed individual BMI trajectories, producing intercepts (baseline BMI) and slopes (BMI change rates). BMI fluctuation was calculated as the average squared deviation from expected BMI across time points. Associations between BMI changes/fluctuation and (i) 1231 plasma proteins related to cardiometabolic and inflammatory functions and (ii) polygenic risk scores for BMI (PRS<sub>BMI</sub>), as well as interaction effects between PRS<sub>BMI</sub> and baseline BMI on protein-BMI relationships were studied. Within-pair analyses using monozygotic twins were conducted to account for shared confounding factors.</p><p><strong>Results: </strong>A total of 135 proteins were associated with changes in BMI over 40 years, while 17 proteins were linked to fluctuation in BMI: 12 associations (10 with BMI changes and 2 with fluctuation) remained significant in within-twin pair analyses. PRS<sub>BMI</sub> was associated with BMI changes but not with fluctuation. PRSBMI-protein interactions explaining BMI changes or fluctuation were found, though a single interaction between the antigen CD72 protein and baseline BMI was observed.</p><p><strong>Conclusion: </strong>This study highlights significant associations between plasma proteins and long-term BMI changes and fluctuations, with no evidence of PRS<sub>BMI</sub>-protein interactions influencing BMI trends. These findings underscore the substantial role of environmental factors in shaping proteome-BMI associations over adulthood.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4000,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Proteomic associations with fluctuation and long-term changes in BMI: A 40-year follow-up study.\",\"authors\":\"Alvaro Obeso, Gabin Drouard, Teemu Palviainen, Xiaoling Wang, Miina Ollikainen, Karri Silventoinen, Jaakko Kaprio\",\"doi\":\"10.1111/dom.16448\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>While some studies have explored associations between weight change and blood proteins, most have been intervention-based, offering limited insight into proteomic associations with long-term weight gain. It remains unclear whether plasma proteins are related to BMI fluctuation over time. This study investigates associations of long-term BMI changes and fluctuations with over 1000 plasma proteins involved in cardiometabolic and inflammation functions.</p><p><strong>Data and methods: </strong>The study included 304 Finnish adult twins (117 men) born before 1958 from the Older Finnish Twin Cohort, with BMI data spanning five time points (1975, 1981, 1990, 2011 and 2012-2014). Proteomic data were derived from blood samples collected at the last BMI measurement. Linear mixed-effects models analysed individual BMI trajectories, producing intercepts (baseline BMI) and slopes (BMI change rates). BMI fluctuation was calculated as the average squared deviation from expected BMI across time points. Associations between BMI changes/fluctuation and (i) 1231 plasma proteins related to cardiometabolic and inflammatory functions and (ii) polygenic risk scores for BMI (PRS<sub>BMI</sub>), as well as interaction effects between PRS<sub>BMI</sub> and baseline BMI on protein-BMI relationships were studied. Within-pair analyses using monozygotic twins were conducted to account for shared confounding factors.</p><p><strong>Results: </strong>A total of 135 proteins were associated with changes in BMI over 40 years, while 17 proteins were linked to fluctuation in BMI: 12 associations (10 with BMI changes and 2 with fluctuation) remained significant in within-twin pair analyses. PRS<sub>BMI</sub> was associated with BMI changes but not with fluctuation. PRSBMI-protein interactions explaining BMI changes or fluctuation were found, though a single interaction between the antigen CD72 protein and baseline BMI was observed.</p><p><strong>Conclusion: </strong>This study highlights significant associations between plasma proteins and long-term BMI changes and fluctuations, with no evidence of PRS<sub>BMI</sub>-protein interactions influencing BMI trends. These findings underscore the substantial role of environmental factors in shaping proteome-BMI associations over adulthood.</p>\",\"PeriodicalId\":158,\"journal\":{\"name\":\"Diabetes, Obesity & Metabolism\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":5.4000,\"publicationDate\":\"2025-05-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Diabetes, Obesity & Metabolism\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/dom.16448\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diabetes, Obesity & Metabolism","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/dom.16448","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
Proteomic associations with fluctuation and long-term changes in BMI: A 40-year follow-up study.
Introduction: While some studies have explored associations between weight change and blood proteins, most have been intervention-based, offering limited insight into proteomic associations with long-term weight gain. It remains unclear whether plasma proteins are related to BMI fluctuation over time. This study investigates associations of long-term BMI changes and fluctuations with over 1000 plasma proteins involved in cardiometabolic and inflammation functions.
Data and methods: The study included 304 Finnish adult twins (117 men) born before 1958 from the Older Finnish Twin Cohort, with BMI data spanning five time points (1975, 1981, 1990, 2011 and 2012-2014). Proteomic data were derived from blood samples collected at the last BMI measurement. Linear mixed-effects models analysed individual BMI trajectories, producing intercepts (baseline BMI) and slopes (BMI change rates). BMI fluctuation was calculated as the average squared deviation from expected BMI across time points. Associations between BMI changes/fluctuation and (i) 1231 plasma proteins related to cardiometabolic and inflammatory functions and (ii) polygenic risk scores for BMI (PRSBMI), as well as interaction effects between PRSBMI and baseline BMI on protein-BMI relationships were studied. Within-pair analyses using monozygotic twins were conducted to account for shared confounding factors.
Results: A total of 135 proteins were associated with changes in BMI over 40 years, while 17 proteins were linked to fluctuation in BMI: 12 associations (10 with BMI changes and 2 with fluctuation) remained significant in within-twin pair analyses. PRSBMI was associated with BMI changes but not with fluctuation. PRSBMI-protein interactions explaining BMI changes or fluctuation were found, though a single interaction between the antigen CD72 protein and baseline BMI was observed.
Conclusion: This study highlights significant associations between plasma proteins and long-term BMI changes and fluctuations, with no evidence of PRSBMI-protein interactions influencing BMI trends. These findings underscore the substantial role of environmental factors in shaping proteome-BMI associations over adulthood.
期刊介绍：
Diabetes, Obesity and Metabolism is primarily a journal of clinical and experimental pharmacology and therapeutics covering the interrelated areas of diabetes, obesity and metabolism. The journal prioritises high-quality original research that reports on the effects of new or existing therapies, including dietary, exercise and lifestyle (non-pharmacological) interventions, in any aspect of metabolic and endocrine disease, either in humans or animal and cellular systems. ‘Metabolism’ may relate to lipids, bone and drug metabolism, or broader aspects of endocrine dysfunction. Preclinical pharmacology, pharmacokinetic studies, meta-analyses and those addressing drug safety and tolerability are also highly suitable for publication in this journal. Original research may be published as a main paper or as a research letter.
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