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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\u2010induced transcriptomic responses (absolute fold change \u22651.5 and\n                    <jats:italic>P<\/jats:italic>\n                    \u22640.05) were comparable in IWAT, BAT, and liver (~800 genes). MR\u2010induced effects were largely restricted to IWAT and liver (~2400 genes). Pathway enrichment and gene\u2010coexpression 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\u2010regulated in MR\u2010treated IWAT and liver (FDR\u22640.07\u20130.3). BAT demonstrated consistent down\u2010regulation of PPAR\u2010signaling under CR and MR, whereas muscle was largely unaffected. Interactome analysis identified CR\u2010specific down\u2010regulation of cytoskeletal matrix components in IWAT and MR\u2010specific up\u2010regulation of ribosomal genes in liver (FDR\u22640.001). Transcriptomic down\u2010regulation 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.\u2014Ghosh, S., Wanders, D., Stone, K. P., Van, N. T., Cortez, C. C., Gettys, T. W. A systems biology analysis of the unique and overlapping transcriptional responses to caloric restriction and dietary methionine restriction in rats.\n                    <jats:italic>FASEB J<\/jats:italic>\n                    . 28, 2577\u20132590 (2014).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.14-249458","type":"journal-article","created":{"date-parts":[[2014,2,27]],"date-time":"2014-02-27T00:11:23Z","timestamp":1393459883000},"page":"2577-2590","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["A systems biology analysis of the unique and overlapping transcriptional responses to caloric restriction and dietary methionine restriction in rats"],"prefix":"10.1096","volume":"28","author":[{"given":"Sujoy","family":"Ghosh","sequence":"first","affiliation":[{"name":"Laboratory of Computational Biology Pennington Biomedical Research Center Baton Rouge Louisiana USA"},{"name":"Laboratory of Nutrient Sensing and Adipocyte Signaling Pennington Biomedical Research Center Baton Rouge Louisiana USA"},{"name":"Cardiovascular and Metabolic Disorders Research Program Duke\u2013National University of Singapore Graduate Medical School Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Desiree","family":"Wanders","sequence":"additional","affiliation":[{"name":"Laboratory of Nutrient Sensing and Adipocyte Signaling Pennington Biomedical Research Center Baton Rouge Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten P.","family":"Stone","sequence":"additional","affiliation":[{"name":"Laboratory of Nutrient Sensing and Adipocyte Signaling Pennington Biomedical Research Center Baton Rouge Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy T.","family":"Van","sequence":"additional","affiliation":[{"name":"Laboratory of Nutrient Sensing and Adipocyte Signaling Pennington Biomedical Research Center Baton Rouge Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cory C.","family":"Cortez","sequence":"additional","affiliation":[{"name":"Laboratory of Nutrient Sensing and Adipocyte Signaling Pennington Biomedical Research Center Baton Rouge Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas W.","family":"Gettys","sequence":"additional","affiliation":[{"name":"Laboratory of Computational Biology Pennington Biomedical Research Center Baton Rouge Louisiana USA"},{"name":"Laboratory of Nutrient Sensing and Adipocyte Signaling Pennington Biomedical Research Center Baton Rouge Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,2,26]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4757-0731-1_31"},{"key":"e_1_2_7_3_1","first-page":"155","article-title":"The effect of retarded growth upon the length of life span and upon the ultimate body size. 1935","volume":"5","author":"McCay C. 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