Serum metabonomics coupled with Ingenuity Pathway Analysis characterizes metabolic perturbations in response to hypothyroidism induced by propylthiouracil in rats

J Pharm Biomed Anal. 2013 Jan:72:109-14. doi: 10.1016/j.jpba.2012.09.030. Epub 2012 Oct 8.

Abstract

A serum metabonomic profiling method based on ultra-performance liquid chromatography/time-of-flight mass spectrometry (UHPLC/TOF-MS) was applied to investigate the metabolic changes in hypothyroid rats induced by propylthiouracil (PTU). With Significance Analysis of Microarray (SAM) for classification and selection of biomarkers, 13 potential biomarkers in rat serum were screened out. Furthermore, Ingenuity Pathway Analysis (IPA) was introduced to deeply analyze unique pathways of hypothyroidism that were primarily involved in sphingolipid metabolism, fatty acid transportation, phospholipid metabolism and phenylalanine metabolism. Our results demonstrated that the metabonomic approach integrating with IPA was a promising tool for providing a novel methodological clue to systemically dissect the underlying molecular mechanism of hypothyroidism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Chromatography, High Pressure Liquid / methods
  • Fatty Acids / blood
  • Fatty Acids / chemistry
  • Fatty Acids / metabolism
  • Hypothyroidism / blood*
  • Hypothyroidism / chemically induced
  • Male
  • Mass Spectrometry / methods
  • Metabolomics / methods
  • Phenylalanine / blood
  • Phenylalanine / chemistry
  • Phenylalanine / metabolism
  • Phospholipids / blood
  • Phospholipids / chemistry
  • Phospholipids / metabolism
  • Propylthiouracil
  • Rats
  • Rats, Wistar
  • Sphingolipids / blood
  • Sphingolipids / chemistry
  • Sphingolipids / metabolism

Substances

  • Fatty Acids
  • Phospholipids
  • Sphingolipids
  • Phenylalanine
  • Propylthiouracil