Overexpression of Akt1 enhances adipogenesis and leads to lipoma formation in zebrafish.
<h4>Background</h4>Obesity is a complex, multifactorial disorder influenced by the interaction of genetic, epigenetic, and environmental factors. Obesity increases the risk of contracting many chronic diseases or metabolic syndrome. Researchers have established several mammalian models o...
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Public Library of Science (PLoS)
2012-01-01
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| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0036474&type=printable |
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| author | Che-Yu Chu Chi-Fang Chen R Samuel Rajendran Chia-Ning Shen Te-Hao Chen Chueh-Chuan Yen Chih-Kuang Chuang Dar-Shong Lin Chung-Der Hsiao |
| author_facet | Che-Yu Chu Chi-Fang Chen R Samuel Rajendran Chia-Ning Shen Te-Hao Chen Chueh-Chuan Yen Chih-Kuang Chuang Dar-Shong Lin Chung-Der Hsiao |
| author_sort | Che-Yu Chu |
| collection | DOAJ |
| description | <h4>Background</h4>Obesity is a complex, multifactorial disorder influenced by the interaction of genetic, epigenetic, and environmental factors. Obesity increases the risk of contracting many chronic diseases or metabolic syndrome. Researchers have established several mammalian models of obesity to study its underlying mechanism. However, a lower vertebrate model for conveniently performing drug screening against obesity remains elusive. The specific aim of this study was to create a zebrafish obesity model by over expressing the insulin signaling hub of the Akt1 gene.<h4>Methodology/principal findings</h4>Skin oncogenic transformation screening shows that a stable zebrafish transgenic of Tg(krt4Hsa.myrAkt1)(cy18) displays severely obese phenotypes at the adult stage. In Tg(krt4:Hsa.myrAkt1)(cy18), the expression of exogenous human constitutively active Akt1 (myrAkt1) can activate endogenous downstream targets of mTOR, GSK-3α/β, and 70S6K. During the embryonic to larval transitory phase, the specific over expression of myrAkt1 in skin can promote hypertrophic and hyperplastic growth. From 21 hour post-fertilization (hpf) onwards, myrAkt1 transgene was ectopically expressed in several mesenchymal derived tissues. This may be the result of the integration position effect. Tg(krt4:Hsa.myrAkt1)(cy18) caused a rapid increase of body weight, hyperplastic growth of adipocytes, abnormal accumulation of fat tissues, and blood glucose intolerance at the adult stage. Real-time RT-PCR analysis showed the majority of key genes on regulating adipogenesis, adipocytokine, and inflammation are highly upregulated in Tg(krt4:Hsa.myrAkt1)(cy18). In contrast, the myogenesis- and skeletogenesis-related gene transcripts are significantly downregulated in Tg(krt4:Hsa.myrAkt1)(cy18), suggesting that excess adipocyte differentiation occurs at the expense of other mesenchymal derived tissues.<h4>Conclusion/significance</h4>Collectively, the findings of this study provide direct evidence that Akt1 signaling plays an important role in balancing normal levels of fat tissue in vivo. The obese zebrafish examined in this study could be a new powerful model to screen novel drugs for the treatment of human obesity. |
| format | Article |
| id | doaj-art-0a90e338f44a43daa82f8b77419aafe6 |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj-art-0a90e338f44a43daa82f8b77419aafe62025-08-20T03:11:48ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0175e3647410.1371/journal.pone.0036474Overexpression of Akt1 enhances adipogenesis and leads to lipoma formation in zebrafish.Che-Yu ChuChi-Fang ChenR Samuel RajendranChia-Ning ShenTe-Hao ChenChueh-Chuan YenChih-Kuang ChuangDar-Shong LinChung-Der Hsiao<h4>Background</h4>Obesity is a complex, multifactorial disorder influenced by the interaction of genetic, epigenetic, and environmental factors. Obesity increases the risk of contracting many chronic diseases or metabolic syndrome. Researchers have established several mammalian models of obesity to study its underlying mechanism. However, a lower vertebrate model for conveniently performing drug screening against obesity remains elusive. The specific aim of this study was to create a zebrafish obesity model by over expressing the insulin signaling hub of the Akt1 gene.<h4>Methodology/principal findings</h4>Skin oncogenic transformation screening shows that a stable zebrafish transgenic of Tg(krt4Hsa.myrAkt1)(cy18) displays severely obese phenotypes at the adult stage. In Tg(krt4:Hsa.myrAkt1)(cy18), the expression of exogenous human constitutively active Akt1 (myrAkt1) can activate endogenous downstream targets of mTOR, GSK-3α/β, and 70S6K. During the embryonic to larval transitory phase, the specific over expression of myrAkt1 in skin can promote hypertrophic and hyperplastic growth. From 21 hour post-fertilization (hpf) onwards, myrAkt1 transgene was ectopically expressed in several mesenchymal derived tissues. This may be the result of the integration position effect. Tg(krt4:Hsa.myrAkt1)(cy18) caused a rapid increase of body weight, hyperplastic growth of adipocytes, abnormal accumulation of fat tissues, and blood glucose intolerance at the adult stage. Real-time RT-PCR analysis showed the majority of key genes on regulating adipogenesis, adipocytokine, and inflammation are highly upregulated in Tg(krt4:Hsa.myrAkt1)(cy18). In contrast, the myogenesis- and skeletogenesis-related gene transcripts are significantly downregulated in Tg(krt4:Hsa.myrAkt1)(cy18), suggesting that excess adipocyte differentiation occurs at the expense of other mesenchymal derived tissues.<h4>Conclusion/significance</h4>Collectively, the findings of this study provide direct evidence that Akt1 signaling plays an important role in balancing normal levels of fat tissue in vivo. The obese zebrafish examined in this study could be a new powerful model to screen novel drugs for the treatment of human obesity.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0036474&type=printable |
| spellingShingle | Che-Yu Chu Chi-Fang Chen R Samuel Rajendran Chia-Ning Shen Te-Hao Chen Chueh-Chuan Yen Chih-Kuang Chuang Dar-Shong Lin Chung-Der Hsiao Overexpression of Akt1 enhances adipogenesis and leads to lipoma formation in zebrafish. PLoS ONE |
| title | Overexpression of Akt1 enhances adipogenesis and leads to lipoma formation in zebrafish. |
| title_full | Overexpression of Akt1 enhances adipogenesis and leads to lipoma formation in zebrafish. |
| title_fullStr | Overexpression of Akt1 enhances adipogenesis and leads to lipoma formation in zebrafish. |
| title_full_unstemmed | Overexpression of Akt1 enhances adipogenesis and leads to lipoma formation in zebrafish. |
| title_short | Overexpression of Akt1 enhances adipogenesis and leads to lipoma formation in zebrafish. |
| title_sort | overexpression of akt1 enhances adipogenesis and leads to lipoma formation in zebrafish |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0036474&type=printable |
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