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Open AccessArticle

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

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Department of Food Science, Aarhus University, Agro Food Park 48, DK-8200 Aarhus N, Denmark
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DuPont Nutrition Biosciences ApS, DK-8220 Brabrand, Aarhus, Denmark
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E. I. duPont de Nemours and Company, Inc., Haskell R&D Center, Newark, DE 19711, USA
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Global Health and Nutrition Science, DuPont Nutrition and Health, FI-02460 Kantvik, Finland
*
Author to whom correspondence should be addressed.
Metabolites 2020, 10(3), 80; https://doi.org/10.3390/metabo10030080
Received: 21 January 2020 / Revised: 18 February 2020 / Accepted: 24 February 2020 / Published: 25 February 2020
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. View Full-Text
Keywords: obesity; multi-omics; metabolomics; transcriptomics; metagenomics; pathway analysis; systems biology obesity; multi-omics; metabolomics; transcriptomics; metagenomics; pathway analysis; systems biology
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Sundekilde, U.K.; Yde, C.C.; Honore, A.H.; Caverly Rae, J.M.; Burns, F.R.; Mukerji, P.; Mawn, M.P.; Stenman, L.; Dragan, Y.; Glover, K.; Jensen, H.M. An Integrated Multi-Omics Analysis Defines Key Pathway Alterations in a Diet-Induced Obesity Mouse Model. Metabolites 2020, 10, 80.

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