Investigating correlations in the altered metabolic profiles of obese and diabetic subjects in a South Indian Asian population using an NMR-based metabolomic approach
Investigating correlations in the altered metabolic profiles of obese and diabetic subjects in a South Indian Asian population using an NMR-based metabolomic approach
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DOI：
10.1039/c4mb00507d
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发表时间：
2015-01-01
影响因子：
--
通讯作者：
Dorai, Kavita
中科院分区：
文献类型：
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作者：
Gogna, Navdeep;Krishna, Murahari;Dorai, Kavita
众所周知，肥胖/高体重指数（BMI）在胰岛素抵抗和2型糖尿病（T2 DM）的演变中起关键作用。然而，其贡献背后的确切机制仍不完全清楚。这项工作的重点是基于NMR的代谢组学研究的糖尿病，肥胖的南印度亚洲受试者的血清配置文件。进行1H-11 D和2D NMR实验以描绘肥胖糖尿病受试者的改变的代谢模式，并使用多变量统计方法来鉴定对四个不同受试者组的样品中的差异有显著贡献的代谢物：具有低和高BMI的糖尿病和非糖尿病受试者。我们的分析显示，与非糖尿病低BMI（对照）组相比，T2 DM高BMI组具有更高浓度的饱和脂肪酸、某些氨基酸（亮氨酸、异亮氨酸、赖氨酸、脯氨酸、苏氨酸、缬氨酸、谷氨酰胺、苯丙氨酸、组氨酸）、乳酸、3-羟基丁酸、胆碱、3，7-二甲基尿酸、泛酸、肌醇、山梨糖醇、甘油和葡萄糖。在这19种鉴定的显著代谢物中，与对照受试者相比，肥胖非糖尿病受试者中饱和脂肪酸、乳酸盐、缬氨酸、异亮氨酸和苯丙氨酸的水平也更高，这意味着这组代谢物可被鉴定为高BMI受试者中糖尿病发作的潜在生物标志物。我们的工作验证了基于NMR的代谢组学与多变量统计分析相结合的实用性，以提供对高BMI糖尿病受试者中受到干扰的潜在代谢途径的见解。
It is well known that obesity/high body mass index (BMI) plays a key role in the evolution of insulin resistance and type-2 diabetes mellitus (T2DM). However, the exact mechanism underlying its contribution is still not fully understood. This work focuses on an NMR-based metabolomic investigation of the serum profiles of diabetic, obese South Indian Asian subjects. H-1 1D and 2D NMR experiments were performed to profile the altered metabolic patterns of obese diabetic subjects and multivariate statistical methods were used to identify metabolites that contributed significantly to the differences in the samples of four different subject groups: diabetic and non-diabetic with low and high BMIs. Our analysis revealed that the T2DM-high BMI group has higher concentrations of saturated fatty acids, certain amino acids (leucine, isoleucine, lysine, proline, threonine, valine, glutamine, phenylalanine, histidine), lactic acid, 3-hydroxybutyric acid, choline, 3,7-dimethyluric acid, pantothenic acid, myoinositol, sorbitol, glycerol, and glucose, as compared to the non-diabetic-low BMI (control) group. Of these 19 identified significant metabolites, the levels of saturated fatty acids, lactate, valine, isoleucine, and phenylalanine are also higher in obese non-diabetic subjects as compared to control subjects, implying that this set of metabolites could be identified as potential biomarkers for the onset of diabetes in subjects with a high BMI. Our work validates the utility of NMR-based metabolomics in conjunction with multivariate statistical analysis to provide insights into the underlying metabolic pathways that are perturbed in diabetic subjects with a high BMI.