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身体成分和代谢组学在艾伯塔省体育活动和乳腺癌预防试验中。

Body Composition and Metabolomics in the Alberta Physical Activity and Breast Cancer Prevention Trial.

机构信息

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.

Department of Cancer Epidemiology and Prevention Research, Cancer Care Alberta, Alberta Health Services, Edmonton, AB, Canada.

出版信息

J Nutr. 2022 Feb 8;152(2):419-428. doi: 10.1093/jn/nxab388.

Abstract

BACKGROUND

Obesity is correlated with many biomarkers, but the extent to which these correlate with underlying body composition is poorly understood.

OBJECTIVES

Our objectives were to 1) describe/compare distinct contributions of fat/lean mass with BMI-metabolite correlations and 2) identify novel metabolite biomarkers of fat/lean mass.

METHODS

The Alberta Physical Activity and Breast Cancer Prevention Trial was a 2-center randomized trial of healthy, inactive, postmenopausal women (n = 304). BMI (in kg/m2) was calculated using weight and height, whereas DXA estimated fat/lean mass. Ultra-performance liquid chromatography and mass spectrometry measured relative concentrations of serum metabolite concentrations. We estimated partial Pearson correlations between 1052 metabolites and BMI, adjusting for age, smoking, and site. Fat mass index (FMI; kg/m2) and lean mass index (LMI; kg/m2) correlations were estimated similarly, with mutual adjustment to evaluate independent effects.

RESULTS

Using a Bonferroni-corrected α level <4.75 × 10-5,  we observed 53 BMI-correlated metabolites (|r| = 0.24-0.42). Of those, 21 were robustly correlated with FMI (|r| > 0.20), 25 modestly (0.10 ≤ |r| ≤ 0.20), and 7 virtually null (|r| < 0.10). Ten of 53 were more strongly correlated with LMI than with FMI. Examining non-BMI-correlated metabolites, 6 robustly correlated with FMI (|r| = 0.24-0.31) and 2 with LMI (r = 0.25-0.26). For these, correlations for fat and lean mass were in opposing directions compared with BMI-correlated metabolites, in which correlations were mostly in the same direction.

CONCLUSIONS

Our results demonstrate how a thorough evaluation of the components of fat and lean mass, along with BMI, provides a more accurate assessment of the associations between body composition and metabolites than BMI alone. Such an assessment makes evident that some metabolites correlated with BMI predominantly reflect lean mass rather than fat, and some metabolites related to body composition are not correlated with BMI. Correctly characterizing these relations is important for an accurate understanding of how and why obesity is associated with disease.

摘要

背景

肥胖与许多生物标志物相关,但这些标志物与基础身体成分的相关性尚不清楚。

目的

我们的目的是 1)描述/比较脂肪/瘦体重与 BMI-代谢物相关性的不同贡献,2)确定脂肪/瘦体重的新型代谢物生物标志物。

方法

艾伯塔省体育活动与乳腺癌预防试验是一项针对健康、不活跃、绝经后妇女(n=304)的 2 中心随机试验。BMI(kg/m2)通过体重和身高计算,而 DXA 估计脂肪/瘦体重。超高效液相色谱和质谱法测量血清代谢物浓度的相对浓度。我们估计了 1052 种代谢物与 BMI 之间的部分 Pearson 相关性,调整了年龄、吸烟和地点因素。脂肪质量指数(FMI;kg/m2)和瘦质量指数(LMI;kg/m2)的相关性也以类似的方式进行了估计,通过相互调整来评估独立影响。

结果

使用 Bonferroni 校正后的 α 值<4.75×10-5,我们观察到与 BMI 相关的 53 种代谢物(|r|=0.24-0.42)。其中,21 种与 FMI 强相关(|r|>0.20),25 种中度相关(0.10≤|r|≤0.20),7 种几乎无关(|r|<0.10)。在 53 种代谢物中,有 10 种与 LMI 的相关性强于与 FMI 的相关性。在检查非 BMI 相关的代谢物时,有 6 种与 FMI 强相关(|r|=0.24-0.31),有 2 种与 LMI 强相关(r=0.25-0.26)。对于这些代谢物,与脂肪和瘦体重的相关性与 BMI 相关的代谢物相反,在这些代谢物中,相关性大多在同一方向。

结论

我们的结果表明,对脂肪和瘦体重以及 BMI 成分进行全面评估,比单独使用 BMI 更能准确评估身体成分与代谢物之间的关联。这种评估清楚地表明,一些与 BMI 相关的代谢物主要反映瘦体重而不是脂肪,而一些与身体成分相关的代谢物与 BMI 不相关。正确描述这些关系对于准确理解肥胖与疾病的关联方式和原因非常重要。

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