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Endocrinology. 2014 Jun;155(6):2199-212. doi: 10.1210/en.2013-1938. Epub 2014 Mar 10.

Hyperplasia and cellularity changes in IGF-1-overexpressing skeletal muscle of crucian carp.

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  • 1Key Laboratory of Aquatic Biodiversity and Conservation of the Chinese Academy of Sciences (D.L., Q.L., G.Z., X.P., X.C., X.D., Z.Z., G.S., X.J., X.C., D.H., J.H., Z.Y.), Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei, China; and University of Chinese Academy of Sciences (D.L., G.Z., X.P., X.C., X.D., Z.Z., G.S.), Beijing, China.


The zebrafish skeletal muscle-specific promoter mylz2 was used to cause crucian carp overexpression of the zebrafish IGF-1 cDNA. In stable transgenic germline F1 progenies, a 5-fold increase in the level of IGF-1 in skeletal muscle was observed. Evident skeletal muscle hyperplasia was observed in the transgenic fish through histologic analysis. By analyzing the RNA sequencing transcriptome of the skeletal muscle of IGF-1 transgenic fish and nontransgenic control fish at 15 months of age, 10 966 transcripts with significant expression levels were identified with definite gene descriptions based on the corresponding zebrafish genome information. Based on the results of our RNA sequencing transcriptome profiling analysis and the results of the real-time quantitative PCR analysis performed to confirm the skeletal muscle transcriptomics analysis, several pathways, including IGF-1 signaling, aerobic metabolism, and protein degradation, were found to be activated in the IGF-1-overexpressing transgenic fish. Intriguingly, our transcriptional expression and protein assays indicated that the overexpression of IGF-1 stimulated a significant shift in the myofiber type toward a more oxidative slow muscle type. Although the body weight was surprisingly decreased by IGF-1 transgenic expression, significantly higher oxygen consumption rates were measured in IGF-1-overexpressing transgenic fish compared with their nontransgenic control fish. These results indicate that the sustained overexpression of IGF-1 in crucian carp skeletal muscle promotes myofiber hyperplasia and cellularity changes, which elicit alterations in the body energy metabolism and skeletal muscle growth.

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