Affordable Access

Access to the full text

An Integrated Multi-Omics Analysis Defines Key Pathway Alterations in a Diet-Induced Obesity Mouse Model

Authors
  • Sundekilde, Ulrik K.1, 2
  • Yde, Christian C.1, 2
  • Honore, Anders H.2
  • Caverly Rae, Jessica M.3
  • Burns, Frank R.3
  • Mukerji, Pushkor3
  • Mawn, Michael P.3
  • Stenman, Lotta4
  • Dragan, Yvonne3
  • Glover, Kyle3
  • Jensen, Henrik M.2
  • 1 Department of Food Science, Aarhus University, Agro Food Park 48, DK-8200 Aarhus N, Denmark
  • 2 DuPont Nutrition Biosciences ApS, DK-8220 Brabrand, Aarhus, Denmark
  • 3 E. I. duPont de Nemours and Company, Inc., Haskell R&D Center, Newark, DE 19711, USA
  • 4 Global Health and Nutrition Science, DuPont Nutrition and Health, FI-02460 Kantvik, Finland
Type
Published Article
Journal
Metabolites
Publisher
MDPI
Publication Date
Feb 25, 2020
Volume
10
Issue
3
Identifiers
DOI: 10.3390/metabo10030080
PMID: 32106514
PMCID: PMC7143281
Source
PubMed Central
Keywords
License
Green

Abstract

Obesity is a multifactorial disease with many complications and related diseases and has become a global epidemic. To thoroughly understand the impact of obesity on whole organism homeostasis, it is helpful to utilize a systems biological approach combining gene expression and metabolomics across tissues and biofluids together with metagenomics of gut microbial diversity. Here, we present a multi-omics study on liver, muscle, adipose tissue, urine, plasma, and feces on mice fed a high-fat diet (HFD). Gene expression analyses showed alterations in genes related to lipid and energy metabolism and inflammation in liver and adipose tissue. The integration of metabolomics data across tissues and biofluids identified major differences in liver TCA cycle, where malate, succinate and oxaloacetate were found to be increased in HFD mice. This finding was supported by gene expression analysis of TCA-related enzymes in liver, where expression of malate dehydrogenase was found to be decreased. Investigations of the microbiome showed enrichment of Lachnospiraceae, Ruminococcaceae, Streptococcaceae and Lactobacillaceae in the HFD group. Our findings help elucidate how the whole organism metabolome and transcriptome are integrated and regulated during obesity.

Report this publication

Statistics

Seen <100 times