Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0177513
Title: An integrative analysis of tissue-specific transcriptomic and metabolomic responses to short-term dietary methionine restriction in mice
Authors: Ghosh S. 
Forney L.A.
Wanders D.
Stone K.P.
Gettys T.W.
Keywords: 2 aminobutyrate
butyric acid derivative
cysteine
glutamic acid
glutathione
methionine
transcription factor
transcription factor NFE2L2
unclassified drug
methionine
transcriptome
adipose tissue
animal experiment
animal tissue
Article
citric acid cycle
controlled study
fatty acid oxidation
fatty acid transport
inguinal region
male
metabolic disorder
metabolomics
mouse
nonhuman
oxidation reduction reaction
oxidative phosphorylation
phenotype
protein restriction
systems biology
tissue specificity
transcriptomics
upregulation
animal
antibody specificity
cluster analysis
gene expression profiling
gene regulatory network
genetics
liver
metabolism
metabolome
procedures
protein restriction
Adipose Tissue
Animals
Cluster Analysis
Diet, Protein-Restricted
Gene Expression Profiling
Gene Regulatory Networks
Liver
Male
Metabolic Networks and Pathways
Metabolome
Metabolomics
Methionine
Mice
Organ Specificity
Transcriptome
Issue Date: 2017
Citation: Ghosh S., Forney L.A., Wanders D., Stone K.P., Gettys T.W. (2017). An integrative analysis of tissue-specific transcriptomic and metabolomic responses to short-term dietary methionine restriction in mice. PLoS ONE 12 (5) : e0177513. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0177513
Abstract: Dietary methionine restriction (MR) produces a coordinated series of transcriptional responses in peripheral tissues that limit fat accretion, remodel lipid metabolism in liver and adipose tissue, and improve overall insulin sensitivity. Hepatic sensing of reduced methionine leads to induction and release of fibroblast growth factor 21 (FGF21), which acts centrally to increase sympathetic tone and activate thermogenesis in adipose tissue. FGF21 also has direct effects in adipose to enhance glucose uptake and oxidation. However, an understanding of how the liver senses and translates reduced dietary methionine into these transcriptional programs remains elusive. A comprehensive systems biology approach integrating transcriptomic and metabolomic readouts in MR-treated mice confirmed that three interconnected mechanisms (fatty acid transport and oxidation, tricarboxylic acid cycle, and oxidative phosphorylation) were activated in MR-treated inguinal adipose tissue. In contrast, the effects of MR in liver involved up-regulation of anti-oxidant responses driven by the nuclear factor, erythroid 2 like 2 transcription factor, NFE2L2. Metabolomic analysis provided evidence for redox imbalance, stemming from large reductions in the master anti-oxidant molecule glutathione coupled with disproportionate increases in ophthalmate and its precursors, glutamate and 2-aminobutyrate. Thus, cysteine and its downstream product, glutathione, emerge as key early hepatic signaling molecules linking dietary MR to its metabolic phenotype. © 2017 Ghosh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/161194
ISSN: 19326203
DOI: 10.1371/journal.pone.0177513
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