title: A systems biology analysis of the unique and overlapping transcriptional responses to caloric restriction and dietary methionine restriction in rats.
abstract: Dietary methionine restriction (MR) and calorie restriction (CR) each improve metabolic health and extend life span. We used comprehensive transcriptome profiling and systems biology analysis to interrogate the unique and overlapping molecular responses in rats provided these dietary regimens for 20 mo after weaning. Microarray analysis was conducted on inguinal white adipose (IWAT), brown adipose tissue (BAT), liver, and skeletal muscle. Compared to controls, CR-induced transcriptomic responses (absolute fold change ≥1.5 and P≤0.05) were comparable in IWAT, BAT, and liver (~800 genes). MR-induced effects were largely restricted to IWAT and liver (~2400 genes). Pathway enrichment and gene-coexpression analyses showed that induction of fatty acid synthesis in IWAT was common to CR and MR, whereas immunity and proinflammatory signaling pathways were specifically down-regulated in MR-treated IWAT and liver (FDR≤0.07-0.3). BAT demonstrated consistent down-regulation of PPAR-signaling under CR and MR, whereas muscle was largely unaffected. Interactome analysis identified CR-specific down-regulation of cytoskeletal matrix components in IWAT and MR-specific up-regulation of ribosomal genes in liver (FDR≤0.001). Transcriptomic down-regulation of inflammation genes by MR in IWAT was consistent with upstream inhibition of STAT3. Together, these results provide an integrated picture of the breadth of transcriptional responses to MR and CR among key metabolic tissues.
authors.affiliation: Laboratory of Computational Biology and Laboratory of Nutrient Sensing and Adipocyte Signaling, Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA; and Cardiovascular and Metabolic Disorders Research Program, Duke-National University of Singapore Graduate Medical School, Singapore.
authors.forename: Sujoy
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Laboratory of Nutrient Sensing and Adipocyte Signaling, Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA; and.
authors.forename: Desiree
authors.initials: D
authors.lastname: Wanders
authors.affiliation: Laboratory of Nutrient Sensing and Adipocyte Signaling, Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA; and.
authors.forename: Kirsten P
authors.initials: KP
authors.lastname: Stone
authors.affiliation: Laboratory of Nutrient Sensing and Adipocyte Signaling, Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA; and.
authors.forename: Nancy T
authors.initials: NT
authors.lastname: Van
authors.affiliation: Laboratory of Nutrient Sensing and Adipocyte Signaling, Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA; and.
authors.forename: Cory C
authors.initials: CC
authors.lastname: Cortez
authors.affiliation: Laboratory of Computational Biology and Laboratory of Nutrient Sensing and Adipocyte Signaling, Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA; and.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Gettys
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism; D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D031204:Caloric Restriction; D015536:Down-Regulation; D020869:Gene Expression Profiling; D007249:Inflammation / Q000503:physiopathology; D008099:Liver / Q000378:metabolism; D008297:Male; D008715:Methionine / Q000172:deficiency*; D018482:Muscle, Skeletal / Q000378:metabolism; D051381:Rats; D049490:Systems Biology; D015854:Up-Regulation
chemical_list: D008715:Methionine
keywords: amino acid sensing; animal models; insulin sensitivity; obesity