Coordinated multitissue transcriptional and plasma metabonomic profiles following acute caloric restriction in mice.
Caloric restriction (CR) increases healthy life span in a range of organisms. The underlying mechanisms are not understood but appear to include changes in gene expression, protein function, and metabolism. Recent studies demonstrate that acute CR alters mortality rates within days in flies. Multitissue transcriptional changes and concomitant metabolic responses to acute CR have not been described. We generated whole genome RNA transcript profiles in liver, skeletal muscle, colon, and hypothalamus and simultaneously measured plasma metabolites using proton nuclear magnetic resonance in mice subjected to acute CR. Liver and muscle showed increased gene expressions associated with fatty acid metabolism and a reduction in those involved in hepatic lipid biosynthesis. Glucogenic amino acids increased in plasma, and gene expression for hepatic gluconeogenesis was enhanced. Increased expression of genes for hormone-mediated signaling and decreased expression of genes involved in protein binding and development occurred in hypothalamus. Cell proliferation genes were decreased and cellular transport genes increased in colon. Acute CR captured many, but not all, hepatic transcriptional changes of long-term CR. Our findings demonstrate a clear transcriptional response across multiple tissues during acute CR, with congruent plasma metabolite changes. Liver and muscle switched gene expression away from energetically expensive biosynthetic processes toward energy conservation and utilization processes, including fatty acid metabolism and gluconeogenesis. Both muscle and colon switched gene expression away from cellular proliferation. Mice undergoing acute CR rapidly adopt many transcriptional and metabolic changes of long-term CR, suggesting that the beneficial effects of CR may require only a short-term reduction in caloric intake.
Selman
Colin
C
Centre for Diabetes and Endocrinology, Department of Medicine, University College London, Rayne Institute, London, United Kingdom. c.selman@ucl.ac.uk
Kerrison
Nicola D
ND
Cooray
Anisha
A
Piper
Matthew D W
MD
Lingard
Steven J
SJ
Barton
Richard H
RH
Schuster
Eugene F
EF
Blanc
Eric
E
Gems
David
D
Nicholson
Jeremy K
JK
Thornton
Janet M
JM
Partridge
Linda
L
Withers
Dominic J
DJ
D000818:Animals; D001774:Blood Chemical Analysis; D031204:Caloric Restriction; D003106:Colon / Q000378:metabolism*; D015536:Down-Regulation; D002149:Energy Intake; D005227:Fatty Acids / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007031:Hypothalamus / Q000378:metabolism*; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism*; D008136:Longevity / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000378:metabolism*; D009928:Organ Specificity; D013047:Specific Pathogen-Free Organisms; D014158:Transcription, Genetic; D015854:Up-Regulation
D005227:Fatty Acids