Obeso Alvaro, Drouard Gabin, Palviainen Teemu, Wang Xiaoling, Ollikainen Miina, Silventoinen Karri, Kaprio Jaakko
Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Science and Technology, University of the Basque Country, Bilbao, Spain.
Helsinki Institute for Demography and Population Health, University of Helsinki, Helsinki, Finland.
Diabetes Obes Metab. 2025 Aug;27(8):4192-4202. doi: 10.1111/dom.16448. Epub 2025 May 8.
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.
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), as well as interaction effects between PRS and baseline BMI on protein-BMI relationships were studied. Within-pair analyses using monozygotic twins were conducted to account for shared confounding factors.
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 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.
This study highlights significant associations between plasma proteins and long-term BMI changes and fluctuations, with no evidence of PRS-protein interactions influencing BMI trends. These findings underscore the substantial role of environmental factors in shaping proteome-BMI associations over adulthood.
虽然一些研究探讨了体重变化与血液蛋白质之间的关联，但大多数研究基于干预措施，对蛋白质组与长期体重增加之间的关联提供的见解有限。血浆蛋白是否与体重指数（BMI）随时间的波动有关仍不清楚。本研究调查了超过1000种参与心脏代谢和炎症功能的血浆蛋白与长期BMI变化及波动之间的关联。
该研究纳入了304名1958年以前出生的芬兰成年双胞胎（117名男性），他们来自芬兰老年双胞胎队列，拥有五个时间点（1975年、1981年、1990年、2011年以及2012 - 2014年）的BMI数据。蛋白质组数据源自最后一次BMI测量时采集的血样。线性混合效应模型分析个体BMI轨迹，得出截距（基线BMI）和斜率（BMI变化率）。BMI波动通过各时间点预期BMI的平均平方偏差来计算。研究了BMI变化/波动与（i）1231种与心脏代谢和炎症功能相关的血浆蛋白以及（ii）BMI的多基因风险评分（PRS）之间的关联，以及PRS与基线BMI对蛋白质 - BMI关系的交互作用。使用同卵双胞胎进行配对内分析以考虑共同的混杂因素。
共有135种蛋白质与40年间的BMI变化相关，17种蛋白质与BMI波动相关：在双胞胎配对内分析中，12种关联（10种与BMI变化相关，2种与波动相关）仍然显著。PRS与BMI变化相关，但与波动无关。发现了PRS - BMI - 蛋白质交互作用可解释BMI变化或波动，不过仅观察到抗原CD72蛋白与基线BMI之间存在单一交互作用。
本研究突出了血浆蛋白与长期BMI变化及波动之间的显著关联，没有证据表明PRS - 蛋白质交互作用会影响BMI趋势。这些发现强调了环境因素在成年期塑造蛋白质组 - BMI关联方面的重要作用。
