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

Ulrik Kræmer Sundekilde, Christian Clement Yde, Anders Hans Honoré, Jessica M. Caverly Rae, Frank R. Burns, Pushkor Mukerji, Michael P. Mawn, Lotta Stenman, Yvonne Dragan, Kyle Glover, Henrik Max Jensen

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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.
Original languageEnglish
Article number80
JournalMetabolites
Volume10
Issue3
Number of pages16
ISSN2218-1989
DOIs
Publication statusPublished - Feb 2020

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