An integrative analysis of tissue-specific transcriptomic and metabolomic responses to short-term dietary methionine restriction in mice

PloS One
Sujoy GhoshThomas W Gettys

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 mast...Continue Reading

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Citations

Apr 1, 2018·Molecular Nutrition & Food Research·Jie YinYulong Yin
Nov 20, 2019·Metabolites·Irene PradasReinald Pamplona
Jul 8, 2020·Molecular Psychiatry·Margot FournierKathryn Hess
Aug 15, 2020·Frontiers in Immunology·Flaminia BardanzelluVassilios Fanos
Feb 13, 2021·Biomedicines·Munehiro KitadaDaisuke Koya
Jun 11, 2021·Nature Communications·Andrea AnnibalAdam Antebi
Jun 11, 2021·Expert Review of Proteomics·Flaminia BardanzelluVassilios Fanos

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Datasets Mentioned

BETA
GSE92463

Methods Mentioned

BETA
nuclear translocation

Software Mentioned

Cytoscape
KEGG Mapper
SOLiDSAGE
IPA
Enrichment Map
Ingenuity Pathway Analysis
DESeq2
EnrichmentMap Cytoscape
Ingenuity
GSEA

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