Metabolic Profiles of Obesity in American Indians: The Strong Heart Family Study

Obesity is a typical metabolic disorder resulting from the imbalance between energy intake and expenditure. American Indians suffer disproportionately high rates of obesity and diabetes. The goal of this study is to identify metabolic profiles of obesity in 431 normoglycemic American Indians participating in the Strong Heart Family Study. Using an untargeted liquid chromatography–mass spectrometry, we detected 1,364 distinct m/z features matched to known compounds in the current metabolomics databases. We conducted multivariate analysis to identify metabolic profiles for obesity, adjusting for standard obesity indicators. After adjusting for covariates and multiple testing, five metabolites were associated with body mass index and seven were associated with waist circumference. Of them, three were associated with both. Majority of the obesity-related metabolites belongs to lipids, e.g., fatty amides, sphingolipids, prenol lipids, and steroid derivatives. Other identified metabolites are amino acids or peptides. Of the nine identified metabolites, five metabolites (oleoylethanolamide, mannosyl-diinositol-phosphorylceramide, pristanic acid, glutamate, and kynurenine) have been previously implicated in obesity or its related pathways. Future studies are warranted to replicate these findings in larger populations or other ethnic groups.肥胖是一类典型的代谢紊乱性疾病，由能量摄入与消耗失衡诱发。美国原住民（American Indians）的肥胖与糖尿病患病率显著高于其他群体。本研究旨在纳入参与强心脏家庭研究（Strong Heart Family Study）的431名血糖正常的美国原住民，以明确肥胖相关的代谢特征谱。本研究采用非靶向液相色谱-质谱联用（untargeted liquid chromatography–mass spectrometry）技术，在现有代谢组学数据库的已知化合物中，鉴定出1364个独特的质荷比（m/z）特征峰。随后通过多变量分析，并结合标准化肥胖指标进行校正，筛选肥胖相关代谢特征。经协变量校正与多重检验校正后，共有5种代谢物与体质量指数相关，7种代谢物与腰围相关，其中3种代谢物同时与二者存在关联。多数肥胖相关代谢物属于脂质类物质，包括脂肪酰胺、鞘脂、异戊烯醇脂质及类固醇衍生物等；其余鉴定出的代谢物则为氨基酸或肽类。在本次鉴定出的9种肥胖相关代谢物中，油酰乙醇酰胺、甘露糖基二肌醇磷酸神经酰胺、植烷酸、谷氨酸及犬尿氨酸这5种代谢物，此前已被证实与肥胖或其相关通路存在关联。未来需开展更大规模队列或其他种族群体的研究，以复现并验证本研究的发现。