Department of Physiological Nursing, University of California, San Francisco, San Francisco, CA, United States.
Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, United States.
Front Endocrinol (Lausanne). 2024 Sep 18;15:1419812. doi: 10.3389/fendo.2024.1419812. eCollection 2024.
Circulating microRNAs show cross-sectional associations with overweight and obesity. Few studies provided data to differentiate between a snapshot perspective on these associations versus how microRNAs characterize prodromal risk from disease pathology and complications. This study assessed longitudinal relationships between circulating microRNAs and weight at multiple time-points in the Diabetes Prevention Program trial.
A subset of participants (n=150) from the Diabetes Prevention Program were included. MicroRNAs were measured from banked plasma using a Fireplex Assay. We used generalized linear mixed models to evaluate relationships between microRNAs and changes in weight at baseline, year-1, and year-2. Logistic regression was used to evaluate whether microRNAs at baseline were associated with weight change after 2 years.
In fully adjusted models that included relevant covariates, seven miRs (i.e., miR-126, miR-15a, miR-192, miR-23a, and miR-27a) were statistically associated with weight over 2 years. MiR-197 and miR-320a remained significant after adjustment for multiple comparisons. Baseline levels of let-7f, miR-17, and miR-320c were significantly associated with 3% weight loss after 2 years in fully adjusted models.
This study provided evidence for longitudinal relationships between circulating microRNAs and weight. Because microRNAs characterize the combined effects of genetic determinants and responses to behavioral determinants, they may provide insights about the etiology of overweight and obesity in the context or risk for common, complex diseases. Additional studies are needed to validate the potential genes and biological pathways that might be targeted by these microRNA biomarkers and have mechanistic implications for weight loss and disease prevention.
循环 microRNA 与超重和肥胖呈横断面关联。很少有研究提供数据来区分这些关联是基于快照视角，还是基于 microRNA 如何从疾病病理和并发症的角度来描述前驱风险。本研究评估了糖尿病预防计划试验中多个时间点循环 microRNA 与体重之间的纵向关系。
纳入了糖尿病预防计划的一部分参与者（n=150）。使用 Fireplex 测定法从储存的血浆中测量 microRNA。我们使用广义线性混合模型评估了 microRNAs 与基线、第 1 年和第 2 年体重变化之间的关系。逻辑回归用于评估基线时的 microRNAs 是否与 2 年后的体重变化相关。
在包含相关协变量的完全调整模型中，七种 miR（即 miR-126、miR-15a、miR-192、miR-23a 和 miR-27a）与 2 年内体重呈统计学相关。在调整多重比较后，miR-197 和 miR-320a 仍然显著。在完全调整模型中，基线水平的 let-7f、miR-17 和 miR-320c 与 2 年后体重下降 3%显著相关。
本研究为循环 microRNA 与体重之间的纵向关系提供了证据。由于 microRNA 可描述遗传决定因素和对行为决定因素的反应的综合效应，因此它们可能为超重和肥胖的病因学提供了在常见复杂疾病的风险背景下的见解。需要进一步的研究来验证这些 microRNA 生物标志物可能靶向的潜在基因和生物学途径，以及它们对体重减轻和疾病预防的潜在机制影响。
