{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T22:18:13Z","timestamp":1783549093216,"version":"3.55.0"},"reference-count":65,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2011,10,17]],"date-time":"2011-10-17T00:00:00Z","timestamp":1318809600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["Z01 ES102205"],"award-info":[{"award-number":["Z01 ES102205"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2012,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    SIRT1 is a highly\u2010conserved NAD\n                    <jats:sup>+<\/jats:sup>\n                    \u2010de\u2010pendent protein deacetylase that plays essential roles in the regulation of energy metabolism, genomic stability, and stress response. Although the functions of SIRT1 in many organs have been extensively studied in tissue\u2010specific knockout mouse models, the systemic role of SIRT1 is still largely unknown as a result of severe developmental defects that result from whole\u2010body knockout in mice. Here, we investigated the systemic functions of SIRT1 in metabolic homeostasis by utilizing a whole\u2010body SIRT1 heterozygous mouse model. These mice are phenotypically normal under standard feeding conditions. However, when chronically challenged with a 40% fat diet, they become obese and insulin resistant, display increased serum cytokine levels, and develop hepatomegaly. Hepatic metabolomic analyses revealed that SIRT1 heterozygous mice have elevated gluconeogenesis and oxidative stress. Surprisingly, they are depleted of glycerolipid metabolites and free fatty acids, yet accumulate lysolipids. Moreover, high\u2010fat feeding induces elevation of serum testosterone levels and enlargement of seminal vesicles in SIRT1 heterozygous males. Microarray analysis of liver mRNA indicates that they have altered expression of genes involved in steroid metabolism and glycerolipid metabolism. Taken together, our findings indicate that SIRT1 plays a vital role in the regulation of systemic energy and steroid hormone homeostasis.\u2014Purushotham, A., Xu, Q., Li, X. Systemic SIRT1 insufficiency results in disruption of energy homeostasis and steroid hormone metabolism upon high\u2010fat\u2010diet feeding.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    26, 656\u2013667 (2012). www.fasebj.org\n                  <\/jats:p>","DOI":"10.1096\/fj.11-195172","type":"journal-article","created":{"date-parts":[[2011,10,18]],"date-time":"2011-10-18T01:10:21Z","timestamp":1318900221000},"page":"656-667","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Systemic SIRT1 insufficiency results in disruption of energy homeostasis and steroid hormone metabolism upon high\u2010fat\u2010diet feeding"],"prefix":"10.1096","volume":"26","author":[{"given":"Aparna","family":"Purushotham","sequence":"first","affiliation":[{"name":"Laboratory of Signal Transduction National Institute of Environmental Health Sciences, Research Triangle Park North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Xu","sequence":"additional","affiliation":[{"name":"Laboratory of Signal Transduction National Institute of Environmental Health Sciences, Research Triangle Park North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoling","family":"Li","sequence":"additional","affiliation":[{"name":"Laboratory of Signal Transduction National Institute of Environmental Health Sciences, Research Triangle Park North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,10,17]]},"reference":[{"key":"e_1_2_16_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/35001622"},{"key":"e_1_2_16_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.110148297"},{"key":"e_1_2_16_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.12.6658"},{"key":"e_1_2_16_5_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.3000"},{"key":"e_1_2_16_6_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pathol.4.110807.092250"},{"key":"e_1_2_16_7_1","doi-asserted-by":"publisher","DOI":"10.3109\/07853890.2010.547211"},{"key":"e_1_2_16_8_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.7.575"},{"key":"e_1_2_16_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07349"},{"key":"e_1_2_16_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03354"},{"key":"e_1_2_16_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2009.02.006"},{"key":"e_1_2_16_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0702509104"},{"key":"e_1_2_16_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2007.07.032"},{"key":"e_1_2_16_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2009.09.009"},{"key":"e_1_2_16_15_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1901210"},{"key":"e_1_2_16_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.122978"},{"key":"e_1_2_16_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2005.07.001"},{"key":"e_1_2_16_18_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.0040295","article-title":"Sirt1 regulates insulin secretion by repressing UCP2 in pancreatic beta cells","volume":"4","author":"Bordone L.","year":"2006","journal-title":"PLoS Biol."},{"key":"e_1_2_16_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02583"},{"key":"e_1_2_16_20_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1839209"},{"key":"e_1_2_16_21_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1385-10.2010"},{"key":"e_1_2_16_22_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0008322","article-title":"Hypothalamic Sirt1 regulates food intake in a rodent model system","volume":"4","author":"Cakir I.","year":"2009","journal-title":"PLoS One"},{"key":"e_1_2_16_23_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2234-10.2010"},{"key":"e_1_2_16_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2010.05.010"},{"key":"e_1_2_16_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.06.050"},{"key":"e_1_2_16_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.07.002"},{"key":"e_1_2_16_27_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1170803"},{"key":"e_1_2_16_28_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1171641"},{"key":"e_1_2_16_29_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.1.38-54.2003"},{"key":"e_1_2_16_30_1","article-title":"Developmental defects and p53 hyperacetylation in Sir2 homolog (SIRT1)\u2010deficient mice","author":"Cheng H. 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