PDF(Pubmed)
Abstract：
While weight gain is associated with a host of chronic illnesses, efforts in obesity have relied on single \"snapshots\" of body mass index (BMI) to guide genetic and molecular discovery. Here, we study >2,000 young adults with metabolomics and proteomics to identify a metabolic liability to weight gain in early adulthood. Using longitudinal regression and penalized regression, we identify a metabolic signature for weight liability, associated with a 2.6% (2.0%-3.2%, p = 7.5 × 10-19) gain in BMI over ≈20 years per SD higher score, after comprehensive adjustment. Identified molecules specified mechanisms of weight gain, including hunger and appetite regulation, energy expenditure, gut microbial metabolism, and host interaction with external exposure. Integration of longitudinal and concurrent measures in regression with Mendelian randomization highlights the complexity of metabolic regulation of weight gain, suggesting caution in interpretation of epidemiologic or genetic effect estimates traditionally used in metabolic research.
摘要：
虽然体重增加与许多慢性疾病有关，肥胖症的努力依赖于体重指数（BMI）的单个“快照”来指导遗传和分子发现。这里,我们通过代谢组学和蛋白质组学研究了>2,000名年轻成年人，以确定成年早期体重增加的代谢倾向。使用纵向回归和惩罚回归，我们确定了体重责任的代谢特征，与2.6%(2.0%-3.2%，p=7.5×10-19)每提高SD分数，BMI增加约20年，经过全面调整。鉴定的分子指定了体重增加的机制，包括饥饿和食欲调节，能量消耗，肠道微生物代谢，以及宿主与外部暴露的相互作用。孟德尔随机化回归中的纵向和并行测量的整合突出了体重增加的代谢调节的复杂性，建议在解释代谢研究中传统使用的流行病学或遗传效应估计时应谨慎。
