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.
Biochim Biophys Acta Mol Basis Dis. 2021 Jul 1;1867(7):166144. doi: 10.1016/j.bbadis.2021.166144. Epub 2021 Apr 14.
Previous genome-wide association analyses for obesity related genes demonstrated the association of BDNF gene variant rs6265 and MC4R gene variant rs17782313 with body mass index (BMI). However, the associated metabolite pathways are still behind the curtain. The aim of the current study is to investigate the associations of metabolic changes in obesity with MC4R gene variant rs17782313 and BDNF variant rs6265. Gas chromatography-mass spectrometry based untargeted metabolomics approach was used and 42 identified serum metabolites were selected for statistical analyses. Significant association of seven metabolites with MC4R gene variant rs17782313 based on obesity and thirty metabolites with obesity dependent BDNF variant rs6265 using additive model (adjusted p < 0.05) was observed. This study highlights the importance of alteration of fatty acid biosynthesis, probably due to high consumption of fats may cause to develop obesity. But obesity is a complex disorder and the full clarification of this complex machinery is still distant. To understand the obesity in a better way, more studies are required to identify remaining metabolites and also mechanism of these metabolic entities.
先前针对肥胖相关基因的全基因组关联分析表明,BDNF 基因变异 rs6265 和 MC4R 基因变异 rs17782313 与体重指数(BMI)有关。然而,相关的代谢途径仍然不为人知。本研究旨在探讨肥胖症中代谢变化与 MC4R 基因变异 rs17782313 和 BDNF 变异 rs6265 的关联。本研究采用基于气相色谱-质谱的非靶向代谢组学方法,对 42 种鉴定出的血清代谢物进行了统计分析。基于肥胖,观察到 MC4R 基因变异 rs17782313 与七种代谢物显著相关,基于肥胖症,BDNF 变异 rs6265 与三十种代谢物显著相关,采用加性模型(调整后 p<0.05)。本研究强调了脂肪酸生物合成改变的重要性,这可能是由于高脂肪的高消耗导致肥胖的发生。但是肥胖是一种复杂的疾病,对这一复杂机制的充分阐明还很遥远。为了更好地理解肥胖,需要进行更多的研究来确定剩余的代谢物,以及这些代谢物的作用机制。