Farooq Sabiha, Rana Sobia, Siddiqui Amna Jabbar, Iqbal Ayesha, Bhatti Adil Anwar, Musharraf Syed Ghulam
H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
Mol Omics. 2023 Oct 30;19(9):697-705. doi: 10.1039/d3mo00112a.
Globally, obesity is a severe health issue. A more precise and practical approach is required to enhance clinical care and drug development. The FTO (fat mass and obesity-associated) gene variant rs1421085 is strongly associated with an increased susceptibility to obesity in numerous populations; however, the precise mechanism behind this association concerning metabolomics is still not understood. This study aims to examine the association between metabolites and obesity-related anthropometric traits based on the variant FTO rs1421085. This study was based on a case-control design involving a total of 542 participants including overweight/obese cases and healthy controls. The blood samples were collected from all the participants. The isolated serum samples were subjected to untargeted metabolomics using GC-MS. The isolated DNA samples were genotyped for the FTO rs1421085 variant. Initially, a total of 42 metabolites were identified on GC-MS, which were subjected to further association analyses. The study observed a significant association of two metabolites, glycerol and 2,3-dihydroxypropyl stearate with FTO gene variant rs1421085 and obesity-related anthropometric traits including % BF, WHtR, WC, and HC. The CT genotype of FTO rs1421085 may greatly increase the risk of overweight/obesity by changing the lipid metabolism-related metabolites. Therefore, this study highlights the significance of biochemical networks in the progression of obesity in carriers of the FTO rs1421085 risk genotype.
在全球范围内，肥胖是一个严重的健康问题。需要一种更精确且实用的方法来加强临床护理和药物研发。FTO（脂肪量和肥胖相关）基因变体rs1421085与众多人群中肥胖易感性增加密切相关；然而，这种关联背后涉及代谢组学的精确机制仍不清楚。本研究旨在基于FTO rs1421085变体，研究代谢物与肥胖相关人体测量特征之间的关联。本研究采用病例对照设计，共纳入542名参与者，包括超重/肥胖病例和健康对照。采集了所有参与者的血样。对分离出的血清样本进行气相色谱-质谱联用的非靶向代谢组学分析。对分离出的DNA样本进行FTO rs1421085变体基因分型。最初，在气相色谱-质谱联用仪上共鉴定出42种代谢物，并对其进行进一步的关联分析。研究发现甘油和2,3-二羟基丙基硬脂酸酯这两种代谢物与FTO基因变体rs1421085以及肥胖相关人体测量特征（包括体脂百分比、腰高比、腰围和臀围）之间存在显著关联。FTO rs1421085的CT基因型可能通过改变脂质代谢相关代谢物，大大增加超重/肥胖的风险。因此，本研究强调了生化网络在FTO rs1421085风险基因型携带者肥胖进展中的重要性。
