Chashmniam Saeed, Hashemi Madani Nahid, Nobakht Mothlagh Ghoochani BiBi Fatemeh, Safari-Alighiarloo Nahid, Khamseh Mohammad E
Department of Chemistry, Sharif University of Technology, Tehran, Iran.
Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran.
Iran J Basic Med Sci. 2020 Feb;23(2):186-194. doi: 10.22038/IJBMS.2019.37885.9004.
The molecular basis of "metabolically healthy obese" and "metabolically unhealthy non-obese" phenotypes is not fully understood. Our objective was to identify metabolite patterns differing in obese (metabolically healthy vs unhealthy (MHO vs MUHO)) and non-obese (metabolically healthy vs unhealthy (MHNO vs MUHNO)) individuals.
This case-control study was performed on 86 subjects stratified into four groups using anthropometric and clinical measurements: MHO (21), MUHO (21), MHNO (22), and MUHNO (22). Serum metabolites were profiled using nuclear magnetic resonance (NMR). Multivariate analysis was applied to uncover discriminant metabolites, and enrichment analysis was performed to identify underlying pathways.
Significantly higher levels of glutamine, asparagine, alanine, L-glutathione reduced, 2-aminobutyrate, taurine, betaine, and choline, and lower level of D-sphingosine were observed in MHO group compared with MUHO. In comparison of MHNO and MUHNO groups, significantly lower levels of alanine, glycine, glutamine, histidine, L-glutathione reduced, and betaine, and higher levels of isoleucine, L-proline, cholic acid, and carnitine appeared in MUHNO individuals. Moreover, significantly affected pathways included amino acid metabolism, urea cycle and ammonia recycling in MUHO subjects and glutathione metabolism, amino acid metabolism, and ammonia recycling in MUHNO members.
Literature review helped us to hint that altered levels of most metabolites might associate to insulin sensitivity and insulin resistance in MHO and MUHNO individuals, respectively. Besides, abnormal amino acid metabolism and ammonia recycling involved in unhealthy phenotypes (MUHO, MUHNO) might be associated with insulin resistance.
“代谢健康的肥胖”和“代谢不健康的非肥胖”表型的分子基础尚未完全明确。我们的目标是确定肥胖个体(代谢健康与不健康(MHO与MUHO))和非肥胖个体(代谢健康与不健康(MHNO与MUHNO))之间存在差异的代谢物模式。
本病例对照研究对86名受试者进行,通过人体测量和临床测量将其分为四组:MHO(21例)、MUHO(21例)、MHNO(22例)和MUHNO(22例)。使用核磁共振(NMR)对血清代谢物进行分析。应用多变量分析来发现具有鉴别作用的代谢物,并进行富集分析以确定潜在途径。
与MUHO组相比,MHO组中谷氨酰胺、天冬酰胺、丙氨酸、还原型L-谷胱甘肽、2-氨基丁酸、牛磺酸、甜菜碱和胆碱水平显著更高,而D-鞘氨醇水平更低。在MHNO组和MUHNO组的比较中,MUHNO个体中丙氨酸、甘氨酸、谷氨酰胺、组氨酸、还原型L-谷胱甘肽和甜菜碱水平显著更低,而异亮氨酸、L-脯氨酸、胆酸和肉碱水平更高。此外,MUHO受试者中显著受影响的途径包括氨基酸代谢、尿素循环和氨再循环,MUHNO个体中包括谷胱甘肽代谢、氨基酸代谢和氨再循环。
文献综述提示我们,大多数代谢物水平的改变可能分别与MHO和MUHNO个体的胰岛素敏感性和胰岛素抵抗相关。此外,不健康表型(MUHO、MUHNO)中涉及的异常氨基酸代谢和氨再循环可能与胰岛素抵抗有关。