LC-MS-Based Metabolomics and Lipidomics Study of High-Density-Lipoprotein-Modulated Glucose Metabolism with an apoA-I Knockout Mouse Model

J Proteome Res. 2019 Jan 4;18(1):48-56. doi: 10.1021/acs.jproteome.8b00290. Epub 2018 Dec 13.

Abstract

Type 2 diabetes mellitus (T2DM) has become a tremendous problem in public health nowadays. High-density lipoprotein (HDL) refers to a group of heterogeneous particles that circulate in blood, and a recent research finds that HDL acts a pivotal part of glucose metabolism. To understand systemic metabolic changes correlated with HDL in glucose metabolism, we applied LC-MS-based metabolomics and lipidomics to detect metabolomic and lipidomic profiles of plasma from apoA-I knockout mice fed a high-fat diet. Multivariate analysis was applied to differentiate apoA-I knockout mice and controls, and potential biomarkers were found. Pathway analysis demonstrated that several metabolic pathways such as aminoacyl-tRNA biosynthesis, arginine and proline metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis were dysregulated in apoA-I knockout mice. This study may provide a new insight into the underlying pathogenesis in T2DM and prove that LC-MS-based metabolomics and lipidomics are powerful approaches in finding potential biomarkers and disturbed pathways.

Keywords: LC−MS; apoA-I; diabetes mellitus; lipidomics; metabolomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoprotein A-I / deficiency
  • Apolipoprotein A-I / genetics
  • Chromatography, Liquid
  • Diabetes Mellitus, Type 2 / metabolism
  • Diet, High-Fat
  • Glucose / metabolism*
  • Lipidomics / methods*
  • Lipoproteins, HDL*
  • Metabolic Networks and Pathways
  • Metabolomics / methods*
  • Mice
  • Mice, Knockout
  • Tandem Mass Spectrometry

Substances

  • Apolipoprotein A-I
  • Lipoproteins, HDL
  • Glucose