Multi-Organ Contribution to the Metabolic Plasma Profile Using Hierarchical Modelling

PLoS One. 2015 Jun 18;10(6):e0129260. doi: 10.1371/journal.pone.0129260. eCollection 2015.

Abstract

Hierarchical modelling was applied in order to identify the organs that contribute to the levels of metabolites in plasma. Plasma and organ samples from gut, kidney, liver, muscle and pancreas were obtained from mice. The samples were analysed using gas chromatography time-of-flight mass spectrometry (GC TOF-MS) at the Swedish Metabolomics centre, Umeå University, Sweden. The multivariate analysis was performed by means of principal component analysis (PCA) and orthogonal projections to latent structures (OPLS). The main goal of this study was to investigate how each organ contributes to the metabolic plasma profile. This was performed using hierarchical modelling. Each organ was found to have a unique metabolic profile. The hierarchical modelling showed that the gut, kidney and liver demonstrated the greatest contribution to the metabolic pattern of plasma. For example, we found that metabolites were absorbed in the gut and transported to the plasma. The kidneys excrete branched chain amino acids (BCAAs) and fatty acids are transported in the plasma to the muscles and liver. Lactic acid was also found to be transported from the pancreas to plasma. The results indicated that hierarchical modelling can be utilized to identify the organ contribution of unknown metabolites to the metabolic profile of plasma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gas Chromatography-Mass Spectrometry / methods
  • Gastrointestinal Tract / metabolism*
  • Kidney / metabolism*
  • Liver / metabolism*
  • Metabolome*
  • Metabolomics / methods*
  • Mice
  • Models, Theoretical*
  • Muscle, Skeletal / metabolism*
  • Pancreas / metabolism*

Grants and funding

This research was supported by the Swedish Research Council, grant no. 2011-6044 (to JT); the Biology of Liver and Pancreatic Development and Disease (BOLD) Marie Curie Initial Training Network (MCITN) within EU’s FP7 programme (to TL, JT, KB, FT, SC, CH, TM); the CNRS and Université Pierre et Marie Curie (to SC, CH); the Institut National de la Santé et de la Recherche Médicale, INSERM (to SC); and the Société Francophone du Diabète and Emergence UPMC (to CH). These funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. AcureOmics AB did not provide support in the form of salaries for authors JT, TM and TL, and did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the "author contributions" section.