PMID- 16882887 OWN - NLM STAT- MEDLINE DCOM- 20061221 LR - 20220129 IS - 1531-2267 (Electronic) IS - 1094-8341 (Linking) VI - 27 IP - 3 DP - 2006 Nov 27 TI - Coordinated multitissue transcriptional and plasma metabonomic profiles following acute caloric restriction in mice. PG - 187-200 AB - 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. FAU - Selman, Colin AU - Selman C AD - Centre for Diabetes and Endocrinology, Department of Medicine, University College London, Rayne Institute, London, United Kingdom. c.selman@ucl.ac.uk FAU - Kerrison, Nicola D AU - Kerrison ND FAU - Cooray, Anisha AU - Cooray A FAU - Piper, Matthew D W AU - Piper MD FAU - Lingard, Steven J AU - Lingard SJ FAU - Barton, Richard H AU - Barton RH FAU - Schuster, Eugene F AU - Schuster EF FAU - Blanc, Eric AU - Blanc E FAU - Gems, David AU - Gems D FAU - Nicholson, Jeremy K AU - Nicholson JK FAU - Thornton, Janet M AU - Thornton JM FAU - Partridge, Linda AU - Partridge L FAU - Withers, Dominic J AU - Withers DJ LA - eng GR - SF19106/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom GR - WT_/Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060801 PL - United States TA - Physiol Genomics JT - Physiological genomics JID - 9815683 RN - 0 (Fatty Acids) SB - IM MH - Animals MH - Blood Chemical Analysis MH - *Caloric Restriction MH - Colon/*metabolism MH - Down-Regulation MH - Energy Intake MH - Fatty Acids/metabolism MH - Gene Expression Profiling MH - *Gene Expression Regulation MH - Hypothalamus/*metabolism MH - Lipid Metabolism MH - Liver/*metabolism MH - Longevity/genetics MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Muscle, Skeletal/*metabolism MH - Organ Specificity MH - Specific Pathogen-Free Organisms MH - *Transcription, Genetic MH - Up-Regulation EDAT- 2006/08/03 09:00 MHDA- 2006/12/22 09:00 CRDT- 2006/08/03 09:00 PHST- 2006/08/03 09:00 [pubmed] PHST- 2006/12/22 09:00 [medline] PHST- 2006/08/03 09:00 [entrez] AID - 00084.2006 [pii] AID - 10.1152/physiolgenomics.00084.2006 [doi] PST - ppublish SO - Physiol Genomics. 2006 Nov 27;27(3):187-200. doi: 10.1152/physiolgenomics.00084.2006. Epub 2006 Aug 1.