Ectopic BAT mUCP-1 overexpression in SKM by delivering a BMP7/PRDM16/PGC-1a gene cocktail or single PRMD16 using non-viral UTMD gene therapy.
Here we present our progress in inducing an ectopic brown adipose tissue (BAT) phenotype in skeletal muscle (SKM) as a potential gene therapy for obesity and its comorbidities. We used ultrasound-targeted microbubble destruction (UTMD), a novel targeted, non-viral approach to gene therapy, to delive...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
2018
|
| Subjects: | |
| Online Access: | http://eprints.uanl.mx/18915/1/30072816 |
| _version_ | 1824415379101843456 |
|---|---|
| author | Chen, Shuyuan Bastarrachea, Raúl A. Shen, Jin Song Laviada Nagel, Antonio Rodríguez Ayala, Ernesto Nava González, Edna Judith Huang, Pintong DeFronzo, Ralph A. Kent, Jack W. Grayburn, Paul A. |
| author_facet | Chen, Shuyuan Bastarrachea, Raúl A. Shen, Jin Song Laviada Nagel, Antonio Rodríguez Ayala, Ernesto Nava González, Edna Judith Huang, Pintong DeFronzo, Ralph A. Kent, Jack W. Grayburn, Paul A. |
| author_sort | Chen, Shuyuan |
| collection | Repositorio Institucional |
| description | Here we present our progress in inducing an ectopic brown adipose tissue (BAT) phenotype in skeletal muscle (SKM) as a potential gene therapy for obesity and its comorbidities. We used ultrasound-targeted microbubble destruction (UTMD), a novel targeted, non-viral approach to gene therapy, to deliver genes in the BAT differentiation pathway into rodent SKM to engineer a thermogenic BAT phenotype with ectopic mUCP-1 overexpression. In parallel, we performed a second protocol using wild-type Ucp-1-null knockout mice to test whether the effects of the gene therapy are UCP-1 dependent. Our main findings were a robust cellular presence of mUCP-1 immunostaining (IHC), significantly higher expression levels of mUCP-1 measured by qRT-PCR, and highest temperature elevation measured by infrared thermography in the treated thigh, achieved in rats after delivering the UTMD-PRDM16/PGC-1a/BMP7/hyPB gene cocktail. Interestingly, the weight loss obtained in the treated rats with the triple gene delivery, never recovered the levels observed in the controls in spite of food intake recovery. Our results establish the feasibility of minimally invasive UTMD gene-based therapy administration in SKM, to induce overexpression of ectopic mUCP-1 after delivery of the thermogenic BAT gene program, and describe systemic effects of this intervention on food intake, weight loss, and thermogenesis. |
| format | Article |
| id | eprints-18915 |
| institution | UANL |
| language | English |
| publishDate | 2018 |
| record_format | eprints |
| spelling | eprints-189152020-06-10T19:22:56Z http://eprints.uanl.mx/18915/ Ectopic BAT mUCP-1 overexpression in SKM by delivering a BMP7/PRDM16/PGC-1a gene cocktail or single PRMD16 using non-viral UTMD gene therapy. Chen, Shuyuan Bastarrachea, Raúl A. Shen, Jin Song Laviada Nagel, Antonio Rodríguez Ayala, Ernesto Nava González, Edna Judith Huang, Pintong DeFronzo, Ralph A. Kent, Jack W. Grayburn, Paul A. R Medicina en General Here we present our progress in inducing an ectopic brown adipose tissue (BAT) phenotype in skeletal muscle (SKM) as a potential gene therapy for obesity and its comorbidities. We used ultrasound-targeted microbubble destruction (UTMD), a novel targeted, non-viral approach to gene therapy, to deliver genes in the BAT differentiation pathway into rodent SKM to engineer a thermogenic BAT phenotype with ectopic mUCP-1 overexpression. In parallel, we performed a second protocol using wild-type Ucp-1-null knockout mice to test whether the effects of the gene therapy are UCP-1 dependent. Our main findings were a robust cellular presence of mUCP-1 immunostaining (IHC), significantly higher expression levels of mUCP-1 measured by qRT-PCR, and highest temperature elevation measured by infrared thermography in the treated thigh, achieved in rats after delivering the UTMD-PRDM16/PGC-1a/BMP7/hyPB gene cocktail. Interestingly, the weight loss obtained in the treated rats with the triple gene delivery, never recovered the levels observed in the controls in spite of food intake recovery. Our results establish the feasibility of minimally invasive UTMD gene-based therapy administration in SKM, to induce overexpression of ectopic mUCP-1 after delivery of the thermogenic BAT gene program, and describe systemic effects of this intervention on food intake, weight loss, and thermogenesis. 2018 Article PeerReviewed text en http://eprints.uanl.mx/18915/1/30072816 http://eprints.uanl.mx Chen, Shuyuan y Bastarrachea, Raúl A. y Shen, Jin Song y Laviada Nagel, Antonio y Rodríguez Ayala, Ernesto y Nava González, Edna Judith y Huang, Pintong y DeFronzo, Ralph A. y Kent, Jack W. y Grayburn, Paul A. (2018) Ectopic BAT mUCP-1 overexpression in SKM by delivering a BMP7/PRDM16/PGC-1a gene cocktail or single PRMD16 using non-viral UTMD gene therapy. Gene Therapy, 25 (7). pp. 497-509. ISSN 0969-7128 doi:10.1038/s41434-018-0036-5 |
| spellingShingle | R Medicina en General Chen, Shuyuan Bastarrachea, Raúl A. Shen, Jin Song Laviada Nagel, Antonio Rodríguez Ayala, Ernesto Nava González, Edna Judith Huang, Pintong DeFronzo, Ralph A. Kent, Jack W. Grayburn, Paul A. Ectopic BAT mUCP-1 overexpression in SKM by delivering a BMP7/PRDM16/PGC-1a gene cocktail or single PRMD16 using non-viral UTMD gene therapy. |
| thumbnail | https://rediab.uanl.mx/themes/sandal5/images/online.png |
| title | Ectopic BAT mUCP-1 overexpression in SKM by delivering a BMP7/PRDM16/PGC-1a gene cocktail or single PRMD16 using non-viral UTMD gene therapy. |
| title_full | Ectopic BAT mUCP-1 overexpression in SKM by delivering a BMP7/PRDM16/PGC-1a gene cocktail or single PRMD16 using non-viral UTMD gene therapy. |
| title_fullStr | Ectopic BAT mUCP-1 overexpression in SKM by delivering a BMP7/PRDM16/PGC-1a gene cocktail or single PRMD16 using non-viral UTMD gene therapy. |
| title_full_unstemmed | Ectopic BAT mUCP-1 overexpression in SKM by delivering a BMP7/PRDM16/PGC-1a gene cocktail or single PRMD16 using non-viral UTMD gene therapy. |
| title_short | Ectopic BAT mUCP-1 overexpression in SKM by delivering a BMP7/PRDM16/PGC-1a gene cocktail or single PRMD16 using non-viral UTMD gene therapy. |
| title_sort | ectopic bat mucp 1 overexpression in skm by delivering a bmp7 prdm16 pgc 1a gene cocktail or single prmd16 using non viral utmd gene therapy |
| topic | R Medicina en General |
| url | http://eprints.uanl.mx/18915/1/30072816 |
| work_keys_str_mv | AT chenshuyuan ectopicbatmucp1overexpressioninskmbydeliveringabmp7prdm16pgc1agenecocktailorsingleprmd16usingnonviralutmdgenetherapy AT bastarrachearaula ectopicbatmucp1overexpressioninskmbydeliveringabmp7prdm16pgc1agenecocktailorsingleprmd16usingnonviralutmdgenetherapy AT shenjinsong ectopicbatmucp1overexpressioninskmbydeliveringabmp7prdm16pgc1agenecocktailorsingleprmd16usingnonviralutmdgenetherapy AT laviadanagelantonio ectopicbatmucp1overexpressioninskmbydeliveringabmp7prdm16pgc1agenecocktailorsingleprmd16usingnonviralutmdgenetherapy AT rodriguezayalaernesto ectopicbatmucp1overexpressioninskmbydeliveringabmp7prdm16pgc1agenecocktailorsingleprmd16usingnonviralutmdgenetherapy AT navagonzalezednajudith ectopicbatmucp1overexpressioninskmbydeliveringabmp7prdm16pgc1agenecocktailorsingleprmd16usingnonviralutmdgenetherapy AT huangpintong ectopicbatmucp1overexpressioninskmbydeliveringabmp7prdm16pgc1agenecocktailorsingleprmd16usingnonviralutmdgenetherapy AT defronzoralpha ectopicbatmucp1overexpressioninskmbydeliveringabmp7prdm16pgc1agenecocktailorsingleprmd16usingnonviralutmdgenetherapy AT kentjackw ectopicbatmucp1overexpressioninskmbydeliveringabmp7prdm16pgc1agenecocktailorsingleprmd16usingnonviralutmdgenetherapy AT grayburnpaula ectopicbatmucp1overexpressioninskmbydeliveringabmp7prdm16pgc1agenecocktailorsingleprmd16usingnonviralutmdgenetherapy |