Zhao Yingya, Nogueira Marina S, Chen Qingxia, Dai Qi, Cai Qiuyin, Wen Wanqing, Lan Qing, Rothman Nathaniel, Gao Yu-Tang, Shu Xiao-Ou, Zheng Wei, Milne Ginger L, Yang Gong
Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Gerontology. 2024;70(2):134-142. doi: 10.1159/000534258. Epub 2023 Nov 15.
Theoretically, some metabolic traits may predispose older individuals to weight loss during aging, leading to increased all-cause mortality and many serious health issues. Biomarkers to robustly predict progressive weight loss during aging are, however, lacking. We prospectively assessed if urinary levels of F2-isoprostanes and their peroxisomal β-oxidation metabolite, 2,3-dinor-5,6-dihydro-15-F2t-isoprostane (F2-IsoP-M), were associated with subsequent weight loss in middle-aged and older women.
Included in the analysis were 2,066 women aged 40-70 years, a subset of a prospective cohort study. F2-isoprostanes (F2-IsoPs) and its β-oxidation metabolite, F2-IsoP-M, were measured in urine using gas chromatography-mass spectrometry. Measurements of anthropometry and exposures to major determinants of body weight were performed at baseline and repeated thrice over 15-year follow-up. The longitudinal associations of F2-IsoP-M and the F2-IsoP-M to its parent compound, F2-IsoP, ratio (MPR) with repeatedly measured weight changes were examined using linear mixed-effect models.
After adjusting for time-varying covariates: energy intake, physical activity, and comorbidity index, among others, levels of F2-IsoP-M and the MPR were both inversely associated with percentage of weight change. Weight in the highest quartile of these two biomarkers was 1.33% (95% CI = -2.41, -0.24) and 1.09% (95% CI = -2.16, -0.02) lower than those in the lowest quartile group, with p for trend of 0.01 and 0.03, respectively. The inverse association was consistently seen across follow-up periods, although appearing stronger with prolonged follow-up. There was no association between the parent compound, F2-IsoPs, and weight change.
This study demonstrates the first piece of evidence to associate F2-IsoP metabolism, peroxisomal β-oxidation, with weight loss in older women. Further investigations into the role of lipid peroxidation and peroxisomal β-oxidation in weight change among older individuals are warranted.
从理论上讲，一些代谢特征可能使老年人在衰老过程中更容易体重减轻，从而导致全因死亡率增加和许多严重的健康问题。然而，目前缺乏能够可靠预测衰老过程中体重逐渐减轻的生物标志物。我们前瞻性地评估了中年及老年女性尿液中F2-异前列腺素及其过氧化物酶体β-氧化代谢产物2,3-二去甲-5,6-二氢-15-F2t-异前列腺素（F2-IsoP-M）的水平是否与随后的体重减轻有关。
纳入分析的是2066名年龄在40至70岁之间的女性，她们是一项前瞻性队列研究的一个子集。使用气相色谱-质谱法测量尿液中的F2-异前列腺素（F2-IsoPs）及其β-氧化代谢产物F2-IsoP-M。在基线时进行人体测量和体重主要决定因素的暴露测量，并在15年的随访中重复进行三次。使用线性混合效应模型研究F2-IsoP-M及其与母体化合物F2-IsoP的比率（MPR）与重复测量的体重变化之间的纵向关联。
在调整了随时间变化的协变量（如能量摄入、身体活动和合并症指数等）后，F2-IsoP-M水平和MPR均与体重变化百分比呈负相关。这两种生物标志物最高四分位数组的体重分别比最低四分位数组低1.33%（95%CI = -2.41，-0.24）和1.09%（95%CI = -2.16，-0.02），趋势p值分别为0.01和0.03。在整个随访期间均观察到负相关，尽管随着随访时间延长相关性似乎更强。母体化合物F2-IsoPs与体重变化之间没有关联。
本研究首次证明了F2-异前列腺素代谢（过氧化物酶体β-氧化）与老年女性体重减轻之间的关联。有必要进一步研究脂质过氧化和过氧化物酶体β-氧化在老年人体重变化中的作用。
