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

TY - JOUR

T1 - An Integrated Multi‐Omics Analysis Defines Key Pathway Alterations in a Diet‐Induced Obesity Mouse Model

AU - Sundekilde, Ulrik Kræmer

AU - Yde, Christian Clement

AU - Honoré, Anders Hans

AU - Caverly Rae, Jessica M.

AU - Burns, Frank R.

AU - Mukerji, Pushkor

AU - Mawn, Michael P.

AU - Stenman, Lotta

AU - Dragan, Yvonne

AU - Glover, Kyle

AU - Jensen, Henrik Max

PY - 2020/2

Y1 - 2020/2

N2 - 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.

AB - 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.

KW - Metabolomics

KW - Metagenomics

KW - Multi-omics

KW - Obesity

KW - Pathway analysis

KW - Systems biology

KW - Transcriptomics

UR - http://www.scopus.com/inward/record.url?scp=85081083007&partnerID=8YFLogxK

U2 - 10.3390/metabo10030080

DO - 10.3390/metabo10030080

M3 - Journal article

C2 - 32106514

SN - 2218-1989

VL - 10

JO - Metabolites

JF - Metabolites

IS - 3

M1 - 80

ER -