Integrated metabolomics analysis of the effect of PPARδ agonist GW501516 on catabolism of BCAAs and carboxylic acids in diabetic mice

• 作者: Li Xiang Juan Nie Li Wang Yu Wang Jingchun Shi Juntong Wei Chi-Wai Lau Zongwei Cai Yu Huang
• 来源期刊: 中国化学快报（英文版）
• 年，卷（期）: 2021,（7）
• 所属期刊栏目: Communications
• 页码范围: 2197-2202
• 页数: 6页
• 语种: 英文

摘要

The peroxisome proliferator-activated receptor (PPARδ) agonists are reported to improve insulin sensitivity, reduce glucose levels, and alleviate dysfunctional lipid metabolism in animal models of type 2 diabetes mellitus. However, the underlying mechanisms remain incompletely understood. Metabolism plays an essential role in the biological system. Monitoring of metabolic changes in response to disease conditions or drug treatment is critical for better understanding of the pathophysiological mechanisms. In this study, metabolic profiling analysis by gas chromatography-mass spectrometry integrated with targeted analysis by liquid chromatography-mass spectrometry was carried out in plasma samples of db/db diabetic mice after six-week treatment of PPARδ agonist GW501516. GW501516 treatment significantly altered levels of metabolites, such as branched-chain amino acids (BCAAs), BCAA metabolites (3-hydroxyisobutyric acid and 3-hydroxyisovaleric acid), long-chain fatty acids, uric acid and ketone bodies (3-hydroxybutyric acid and 2-hydroxybutyric acid) which are all associated with the impaired systemic insulin sensitivity. The present results indicate the beneficial effect of PPARδagonist in alleviating insulin resistance of diabetic mice by favorably modulating metabolic profile, thus providing valuable information in understanding the therapeutic potential of PPARδ agonists in correcting metabolic dysfunction in diabetes.