A systems biology analysis of the unique and overlapping transcriptional responses to caloric restriction and dietary methionine restriction in rats.

Authors:
Sujoy Ghosh
Sujoy Ghosh
Duke-NUS Medical School
Singapore
Desiree Wanders
Desiree Wanders
Laboratory of Nutrient Sensing and Adipocyte Signaling
Kirsten P Stone
Kirsten P Stone
Laboratory of Nutrient Sensing and Adipocyte Signaling
Nancy T Van
Nancy T Van
Laboratory of Nutrient Sensing and Adipocyte Signaling
Cory C Cortez
Cory C Cortez
Louisiana State University
United States
Thomas W Gettys
Thomas W Gettys
Louisiana State University Health Sciences Center
United States

FASEB J 2014 Jun 26;28(6):2577-90. Epub 2014 Feb 26.

Laboratory of Computational Biology and Laboratory of Nutrient Sensing and Adipocyte Signaling, Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA; and.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1096/fj.14-249458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4021438PMC
June 2014
257 Reads

Publication Analysis

Top Keywords

iwat liver
8
unique overlapping
8
bat liver
8
transcriptional responses
8
methionine restriction
8
systems biology
8
dietary methionine
8
biology analysis
8
iwat
7
liver
5
gene-coexpression analyses
4
enrichment gene-coexpression
4
liver ~2400
4
~2400 genes
4
genes pathway
4
pathway enrichment
4
analyses induction
4
iwat common
4
proinflammatory signaling
4
signaling pathways
4

References

(Supplied by CrossRef)
Article in Nutrition
McCay C. M. et al.
Nutrition 1989
Article in FASEB J
Richie J. P. et al.
FASEB J 1994
Article in J. Nutr
Orentreich N. et al.
J. Nutr 1993
Article in J. Nutr
Barzilai N. et al.
J. Nutr 2001

Similar Publications