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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2015,8,18]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    The metabolic syndrome has evolved to be a major health issue globally. The association between genome integrity and metabolic abnormalities is not well understood. Our results indicate that increased DNA damage and persistent activation of the DNA damage response induce adipocyte senescence in DNA polymerase \u03b7 knockout (\n                    <jats:italic>pol<\/jats:italic>\n                    <jats:italic>\u03b7<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) mice. Suppression of adipocyte senescence with a p53 inhibitor, pifithrin-\u03b1, alleviated metabolic abnormalities in\n                    <jats:italic>pol \u03b7<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. An increase or decrease in DNA damage affected the senescence status of adipocytes accordingly, which was also in concordance with the severity of metabolic abnormalities in the\n                    <jats:italic>pol \u03b7<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. Our current results indicate that reduced genome integrity plays a causative role in provoking adipocyte senescence that leads to development of obesity and insulin resistance.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1506954112","type":"journal-article","created":{"date-parts":[[2015,8,3]],"date-time":"2015-08-03T22:49:47Z","timestamp":1438642187000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":72,"title":["Ablation of XP-V gene causes adipose tissue senescence and metabolic abnormalities"],"prefix":"10.1073","volume":"112","author":[{"given":"Yih-Wen","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Harris","sequence":"additional","affiliation":[{"name":"Richard Roudebush Veterans Affairs Medical Center and the Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zafer","family":"Hatahet","sequence":"additional","affiliation":[{"name":"Department of Biological and Physical Sciences, Northwestern State University of Louisiana, Natchitoches, LA 71497"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai-ming","family":"Chou","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2015,8,3]]},"reference":[{"key":"e_1_3_3_1_2","unstructured":"Z Korwek O Alster [The role of the DNA damage response in apoptosis and cell senescence.] Postepy Biochem 60(2):248\u2013262. 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