Metabolite and transcriptome analysis during fasting suggest a role for the p53-Ddit4 axis in major metabolic tissues

BMC Genomics

Research Article

Michael Schupp¹  Erika R Briggs²  Mitchell A Lazar²  Fang Chen³  Andreas Prokesch⁴  Ariane R Pessentheiner⁴  Juliane G Bogner-Strauss⁴  Helmut J Pelzmann⁴  Don Baldwin⁵  Shilpa Rao⁶ 

[1] Department of Endocrinology, Diabetes, and Nutrition and Center for Cardiovascular Research (CCR), Charité University Medicine, Hessische Str. 3-4, 10115, Berlin, Germany;Department of Medicine, and the Institute for Diabetes, Obesity, and Metabolism, Division of Endocrinology, Diabetes, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, 19104, Philadelphia, PA, USA;Department of Microbiology, 201 Johnson Pavilion, Perelman School of Medicine University of Pennsylvania, 3610 Hamilton Walk, 19104, Philadelphia, PA, USA;Institute for Genomics and Bioinformatics, Graz University of Technology, Petersgasse 14, 8010, Graz, Austria;Institute of Biochemistry, Graz University of Technology, Petersgasse 12/2, 8010, Graz, Austria;Pathonomics LLC, Suite 200, 3160 Chestnut St., 19104, Philadelphia, PA, USA;Penn Bioinformatics Core, University of Pennsylvania, 19104, Philadelphia, PA, USA;

关键词: Fasting;    Starvation;    Nutrient deprivation;    Adipose tissue;    p53 signaling;    Ddit4;    Lipolysis;   

DOI  :  10.1186/1471-2164-14-758

 received in 2013-05-31, accepted in 2013-10-31,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundFasting induces specific molecular and metabolic adaptions in most organisms. In biomedical research fasting is used in metabolic studies to synchronize nutritional states of study subjects. Because there is a lack of standardization for this procedure, we need a deeper understanding of the dynamics and the molecular mechanisms in fasting.ResultsWe investigated the dynamic changes of liver gene expression and serum parameters of mice at several time points during a 48 hour fasting experiment and then focused on the global gene expression changes in epididymal white adipose tissue (WAT) as well as on pathways common to WAT, liver, and skeletal muscle. This approach produced several intriguing insights: (i) rather than a sequential activation of biochemical pathways in fasted liver, as current knowledge dictates, our data indicates a concerted parallel response; (ii) this first characterization of the transcriptome signature of WAT of fasted mice reveals a remarkable activation of components of the transcription apparatus; (iii) most importantly, our bioinformatic analyses indicate p53 as central node in the regulation of fasting in major metabolic tissues; and (iv) forced expression of Ddit4, a fasting-regulated p53 target gene, is sufficient to augment lipolysis in cultured adipocytes.ConclusionsIn summary, this combination of focused and global profiling approaches provides a comprehensive molecular characterization of the processes operating during fasting in mice and suggests a role for p53, and its downstream target Ddit4, as novel components in the transcriptional response to food deprivation.

【 授权许可】

Unknown   
© Schupp et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.