Adipose tissue metabolic dysregulation in diet-induced obesity: insights from UHPLC-HRMS-based metabolomics

Abstract

Obesity and related metabolic complications are associated with adipose tissue (AT) dysfunction, which contributes to metabolic inflexibility. However, the underlying mechanisms remain unclear. Our previous studies demonstrated that a high-fat diet (HFD) induces weight gain, increased fat weight, as well as significant metabolite alterations in serum, liver, and cecum in mice. Therefore, this study aims to investigate the effect of HFD on AT metabolites to elucidate their role in obesity progression. To establish a diet-induced obesity model, nine female Kunming mice were fed a high-fat diet (HFD) for 16 weeks and compared with nine control mice maintained on a normal diet. Subcutaneous abdominal adipose tissue samples (SAAT) were analyzed using ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) coupled with orthogonal partial least squares discriminant analysis (OPLS-DA). By metabolic profiling, 48 significantly different metabolites were identified, including phosphatidylcholines (PCs), lysophosphatidylcholines (LysoPCs), O -phosphoethanolamine, linoleic acid, alpha-linolenic acid, proline betaine, and 3-dehydroxycarnitine. These obesity-associated metabolites were mainly involved in glycerophospholipid metabolism, sphingolipid metabolism, and biosynthesis of unsaturated fatty acids. Among these pathways, glycerophospholipid metabolism exhibited the most pronounced disruption. These identified metabolites in SAAT may aid in understanding of the mechanism by which HFD promotes the progression of obesity and related diseases.