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To this end, we have generated a series of recombinant adeno-associated virus vectors of serotypes 1 and 5 encoding mouse Acrp30 cDNAs. The long-term expression of recombinant adeno-associated virus-Acrp30 vectors was tested after intramuscular or intraportal injection in female Sprague\u2013Dawley rats with diet-induced obesity. We show that a single peripheral injection of 10\n                    <jats:sup>12<\/jats:sup>\n                    physical particles of Acrp30-encoding vectors resulted in sustained (up to 280 days) significant reduction in body weight, concomitant with the reduction in daily food intake. Acrp30 treatment resulted in higher peripheral insulin sensitivity measured by the i.p. glucose tolerance test in fasted animals. Ectopic expression of the Acrp30 transgene resulted in modulation of hepatic gluconeogenesis and lipogenesis, as demonstrated by the reduction of the expression of two key genes:\n                    <jats:italic>PEPCK<\/jats:italic>\n                    (phospho\n                    <jats:italic>enol<\/jats:italic>\n                    pyruvate carboxykinase) and\n                    <jats:italic>SREBP-1c<\/jats:italic>\n                    (sterol regulatory element-binding protein 1c) in the liver. These data show successful peripheral therapy in a clinically relevant model for human obesity and insulin resistance.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2333912100","type":"journal-article","created":{"date-parts":[[2003,11,25]],"date-time":"2003-11-25T15:59:06Z","timestamp":1069775946000},"page":"14217-14222","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":206,"title":["Sustained peripheral expression of transgene adiponectin offsets the development of diet-induced obesity in rats"],"prefix":"10.1073","volume":"100","author":[{"given":"Stanislav","family":"Shklyaev","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Powell Gene Therapy Center, and Departments of Pathology and Pharmacology and Therapeutics, University of Florida, Gainesville, FL 32610-0266; and Malcolm Randall Department of Veterans Affairs Medical Center, Gainesville, FL 32608-1135"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Aslanidi","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Powell Gene Therapy Center, and Departments of Pathology and Pharmacology and Therapeutics, University of Florida, Gainesville, FL 32610-0266; 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