Transcriptomic analysis elucidates the enhanced skeletal muscle mass, reduced fat accumulation, and metabolically benign liver in human follistatin-344 transgenic pigs
Follistatin (FST) is an important regulator of skeletal muscle growth and adipose deposition through its ability to bind to several members of the transforming growth factor-β (TGF-β) superfamily, and thus may be a good candidate for future animal breeding programs. However, the molecular mechanisms...
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KeAi Communications Co., Ltd.
2022-01-01
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| Series: | Journal of Integrative Agriculture |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2095311922000235 |
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| author | Ke-ren LONG Xiao-kai LI Ruo-wei ZHANG Yi-ren GU Min-jie DU Xiang-yang XING Jia-xiang DU Miao-miao MAI Jing WANG Long JIN Qian-zi TANG Si-lu HU Ji-deng MA Xun WANG Deng-ke PAN Ming-zhou LI |
| author_facet | Ke-ren LONG Xiao-kai LI Ruo-wei ZHANG Yi-ren GU Min-jie DU Xiang-yang XING Jia-xiang DU Miao-miao MAI Jing WANG Long JIN Qian-zi TANG Si-lu HU Ji-deng MA Xun WANG Deng-ke PAN Ming-zhou LI |
| author_sort | Ke-ren LONG |
| collection | DOAJ |
| description | Follistatin (FST) is an important regulator of skeletal muscle growth and adipose deposition through its ability to bind to several members of the transforming growth factor-β (TGF-β) superfamily, and thus may be a good candidate for future animal breeding programs. However, the molecular mechanisms underlying the phenotypic changes have yet to be clarified in pig. We generated transgenic (TG) pigs that express human FST specifically in skeletal muscle tissues and characterized the phenotypic changes compared with the same tissues in wild-type pigs. The TG pigs showed increased skeletal muscle growth, decreased adipose deposition, and improved metabolism status (P<0.05). Transcriptome analysis detected important roles of the PIK3–AKT signaling pathway, calcium-mediated signaling pathway, and amino acid metabolism pathway in FST-induced skeletal muscle hypertrophy, and depot-specific oxidative metabolism changes in psoas major muscle. Furthermore, the lipid metabolism-related process was changed in adipose tissue in the TG pigs. Gene set enrichment analysis revealed that genes related to lipid synthesis, lipid catabolism, and lipid storage were down-regulated (P<0.01) in the TG pigs for subcutaneous fat, whereas genes related to lipid catabolism were significantly up-regulated (P<0.05) in the TG pigs for retroperitoneal fat compared with their expression levels in wild-type pigs. In liver, genes related to the TGF-β signaling pathway were over-represented in the TG pigs, which is consistent with the inhibitory role of FST in regulating TGF-β signaling. Together, these results provide new insights into the molecular mechanisms underlying the phenotypic changes in pig. |
| format | Article |
| id | doaj-art-8eee8d6df91947929ea4372a6b3af4c0 |
| institution | Kabale University |
| issn | 2095-3119 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Journal of Integrative Agriculture |
| spelling | doaj-art-8eee8d6df91947929ea4372a6b3af4c02025-08-20T03:57:08ZengKeAi Communications Co., Ltd.Journal of Integrative Agriculture2095-31192022-01-012192675269010.1016/j.jia.2022.07.014Transcriptomic analysis elucidates the enhanced skeletal muscle mass, reduced fat accumulation, and metabolically benign liver in human follistatin-344 transgenic pigsKe-ren LONG0Xiao-kai LI1Ruo-wei ZHANG2Yi-ren GU3Min-jie DU4Xiang-yang XING5Jia-xiang DU6Miao-miao MAI7Jing WANG8Long JIN9Qian-zi TANG10Si-lu HU11Ji-deng MA12Xun WANG13Deng-ke PAN14Ming-zhou LI15Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, P.R.ChinaInstitute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, P.R.ChinaInstitute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, P.R.ChinaAnimal Breeding and Genetics Key Laboratory of Sichuan Province, Pig Science Institute, Sichuan Animal Science Academy, Chengdu 610066, P.R.ChinaChengdu Clonorgan Biotechnology Co., Ltd., Chengdu 610041, P.R.ChinaChengdu Clonorgan Biotechnology Co., Ltd., Chengdu 610041, P.R.ChinaChengdu Clonorgan Biotechnology Co., Ltd., Chengdu 610041, P.R.ChinaInstitute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, P.R.ChinaInstitute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, P.R.ChinaInstitute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, P.R.ChinaInstitute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, P.R.ChinaInstitute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, P.R.ChinaInstitute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, P.R.ChinaInstitute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, P.R.ChinaInstitute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, P.R.China; Institute of Organ Transplantation, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu 610072, P.R.China; Correspondence PAN Deng-keInstitute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, P.R.China; Correspondence LI Ming-zhouFollistatin (FST) is an important regulator of skeletal muscle growth and adipose deposition through its ability to bind to several members of the transforming growth factor-β (TGF-β) superfamily, and thus may be a good candidate for future animal breeding programs. However, the molecular mechanisms underlying the phenotypic changes have yet to be clarified in pig. We generated transgenic (TG) pigs that express human FST specifically in skeletal muscle tissues and characterized the phenotypic changes compared with the same tissues in wild-type pigs. The TG pigs showed increased skeletal muscle growth, decreased adipose deposition, and improved metabolism status (P<0.05). Transcriptome analysis detected important roles of the PIK3–AKT signaling pathway, calcium-mediated signaling pathway, and amino acid metabolism pathway in FST-induced skeletal muscle hypertrophy, and depot-specific oxidative metabolism changes in psoas major muscle. Furthermore, the lipid metabolism-related process was changed in adipose tissue in the TG pigs. Gene set enrichment analysis revealed that genes related to lipid synthesis, lipid catabolism, and lipid storage were down-regulated (P<0.01) in the TG pigs for subcutaneous fat, whereas genes related to lipid catabolism were significantly up-regulated (P<0.05) in the TG pigs for retroperitoneal fat compared with their expression levels in wild-type pigs. In liver, genes related to the TGF-β signaling pathway were over-represented in the TG pigs, which is consistent with the inhibitory role of FST in regulating TGF-β signaling. Together, these results provide new insights into the molecular mechanisms underlying the phenotypic changes in pig.http://www.sciencedirect.com/science/article/pii/S2095311922000235follistatintransgenic pigtranscriptomeskeletal muscleliveradipose |
| spellingShingle | Ke-ren LONG Xiao-kai LI Ruo-wei ZHANG Yi-ren GU Min-jie DU Xiang-yang XING Jia-xiang DU Miao-miao MAI Jing WANG Long JIN Qian-zi TANG Si-lu HU Ji-deng MA Xun WANG Deng-ke PAN Ming-zhou LI Transcriptomic analysis elucidates the enhanced skeletal muscle mass, reduced fat accumulation, and metabolically benign liver in human follistatin-344 transgenic pigs Journal of Integrative Agriculture follistatin transgenic pig transcriptome skeletal muscle liver adipose |
| title | Transcriptomic analysis elucidates the enhanced skeletal muscle mass, reduced fat accumulation, and metabolically benign liver in human follistatin-344 transgenic pigs |
| title_full | Transcriptomic analysis elucidates the enhanced skeletal muscle mass, reduced fat accumulation, and metabolically benign liver in human follistatin-344 transgenic pigs |
| title_fullStr | Transcriptomic analysis elucidates the enhanced skeletal muscle mass, reduced fat accumulation, and metabolically benign liver in human follistatin-344 transgenic pigs |
| title_full_unstemmed | Transcriptomic analysis elucidates the enhanced skeletal muscle mass, reduced fat accumulation, and metabolically benign liver in human follistatin-344 transgenic pigs |
| title_short | Transcriptomic analysis elucidates the enhanced skeletal muscle mass, reduced fat accumulation, and metabolically benign liver in human follistatin-344 transgenic pigs |
| title_sort | transcriptomic analysis elucidates the enhanced skeletal muscle mass reduced fat accumulation and metabolically benign liver in human follistatin 344 transgenic pigs |
| topic | follistatin transgenic pig transcriptome skeletal muscle liver adipose |
| url | http://www.sciencedirect.com/science/article/pii/S2095311922000235 |
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