{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T03:27:47Z","timestamp":1781321267057,"version":"3.54.1"},"reference-count":37,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2017,7,31]],"date-time":"2017-07-31T00:00:00Z","timestamp":1501459200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IUBMB Life"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Ultrasound\u2010targeted microbubble destruction (UTMD) is a novel means of tissue\u2010specific gene delivery. This approach systemically infuses transgenes precoupled to gas\u2010filled lipid microbubbles that are burst within the microvasculature of target tissues via an ultrasound signal resulting in release of DNA and transfection of neighboring cells within the tissue. Previous work has shown that adenovirus containing cDNA of <jats:italic>UCP\u20101<\/jats:italic>, injected into the epididymal fat pads in mice, induced localized fat depletion, improving glucose tolerance, and decreasing food intake in obese diabetic mice. Our group recently demonstrated that gene therapy by UTMD achieved beta cell regeneration in streptozotocin (STZ)\u2010treated mice and baboons. We hypothesized that gene therapy with <jats:italic>BMP7\/PRDM16\/PPARGC1A<\/jats:italic> in skeletal muscle (SKM) of obese Zucker diabetic fatty (<jats:italic>fa\/fa<\/jats:italic>) rats using UTMD technology would produce a brown adipose tissue (BAT) phenotype with <jats:italic>UCP\u20101<\/jats:italic> overexpression. This study was designed as a proof of concept (POC) project. Obese Zucker rats were administered plasmid cDNA contructs encoding a gene cocktail with <jats:italic>BMP7\/PRDM16\/PPARGC1A<\/jats:italic> incorporated within microbubbles and intravenously delivered into their left thigh. Controls received UTMD with plasmids driving a <jats:italic>DsRed<\/jats:italic> reporter gene. An ultrasound transducer was directed to the thigh to disrupt the microbubbles within the microcirculation. Blood samples were drawn at baseline, and after treatment to measure glucose, insulin, and free fatty acids levels. SKM was harvested for immunohistochemistry (IHC). Our IHC results showed a reliable pattern of effective UTMD\u2010based gene delivery in enhancing SKM overexpression of the <jats:italic>UCP\u20101<\/jats:italic> gene. This clearly indicates that our plasmid DNA construct encoding the gene combination of <jats:italic>PRDM16, PPARGC1A,<\/jats:italic> and <jats:italic>BMP7<\/jats:italic> reprogrammed adult SKM tissue into brown adipose cells <jats:italic>in vivo<\/jats:italic>. Our pilot established POC showing that the administration of the gene cocktail to SKM in this rat model of genetic obesity using UTMD gene therapy, engineered a BAT phenotype with <jats:italic>UCP\u20101<\/jats:italic> over\u2010expression. \u00a9 2017 IUBMB Life, 69(9):745\u2013755, 2017<\/jats:p>","DOI":"10.1002\/iub.1658","type":"journal-article","created":{"date-parts":[[2017,8,1]],"date-time":"2017-08-01T04:49:49Z","timestamp":1501562989000},"page":"745-755","source":"Crossref","is-referenced-by-count":12,"title":["Engineering brown fat into skeletal muscle using ultrasound\u2010targeted microbubble destruction gene delivery in obese Zucker rats: Proof of concept design"],"prefix":"10.1002","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4034-3062","authenticated-orcid":false,"given":"Raul A.","family":"Bastarrachea","sequence":"first","affiliation":[{"name":"Department of Genetics Texas Biomedical Research Institute San Antonio, TX USA"},{"name":"Southwest National Primate Research Center San Antonio, TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxi","family":"Chen","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical School Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Jack W.","family":"Kent","sequence":"additional","affiliation":[{"name":"Department of Genetics Texas Biomedical Research Institute San Antonio, TX USA"},{"name":"Southwest National Primate Research Center San Antonio, TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edna J.","family":"Nava\u2010Gonzalez","sequence":"additional","affiliation":[{"name":"University of Nuevo Leon School of Nutrition and Public Health Monterrey Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernesto","family":"Rodriguez\u2010Ayala","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias de la Salud Universidad An\u00e1huac Norte M\u00e9xico DF Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel M.","family":"Daadi","sequence":"additional","affiliation":[{"name":"Southwest National Primate Research Center San Antonio, TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Jorge","sequence":"additional","affiliation":[{"name":"Department of Genetics Texas Biomedical Research Institute San Antonio, TX USA"},{"name":"Southwest National Primate Research Center San Antonio, TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo","family":"Laviada\u2010Molina","sequence":"additional","affiliation":[{"name":"Escuela de Ciencias de la Salud Universidad Marista de M\u00e9rida  Yucat\u00e1n, Yucat\u00e1n"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony G.","family":"Comuzzie","sequence":"additional","affiliation":[{"name":"Department of Genetics Texas Biomedical Research Institute San Antonio, TX USA"},{"name":"Southwest National Primate Research Center San Antonio, TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Baylor Research Institute Dallas, TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul A.","family":"Grayburn","sequence":"additional","affiliation":[{"name":"Baylor Research Institute Dallas, TX USA"},{"name":"Baylor University Medical Center Dallas, TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,7,31]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1517\/14712598.5.3.347"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.298.17.2028"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.2147\/DMSO.S7384"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.08.018"},{"key":"e_1_2_6_6_1","first-page":"52","article-title":"Brown fat tissue\u2014a potential target to combat obesity","volume":"113","author":"Ginter E.","year":"2012","journal-title":"Bratisl Lek Listy"},{"key":"e_1_2_6_7_1","first-page":"968218","article-title":"Development of viral vectors for gene therapy for chronic pain","volume":"2011","author":"Huang Y.","year":"2011","journal-title":"Pain Res. 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