|Transcriptomic analysis elucidates the enhanced skeletal muscle mass, reduced fat accumulation, and metabolically benign liver in human follistatin-344 transgenic pigs
|LONG Ke-ren1*, LI Xiao-kai1*, ZHANG Ruo-wei1*, GU Yi-ren2*, DU Min-jie5, XING Xiang-yang5, DU Jia-xiang5, MAI Miao-miao1, WANG Jing1, JIN Long1, TANG Qian-zi1, HU Si-lu1, MA Ji-deng1, WANG Xun1, PAN Deng-ke3, 4, LI Ming-zhou1
1 Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, P.R.China
2 Animal Breeding and Genetics Key Laboratory of Sichuan Province, Pig Science Institute, Sichuan Animal Science Academy, Chengdu 610066, P.R.China
3 Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, P.R.China
4 Institute of Organ Transplantation, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu 610072, P.R.China
5 Chengdu Clonorgan Biotechnology Co., Ltd., Chengdu 610041, P.R.China
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.
Received: 16 June 2021
Accepted: 07 March 2022
This work was supported by grants from the National Key R&D Program of China (2020YFA0509500), the National Natural Science Foundation of China (U19A2036, 32102512, 31872335, and 31802044), the National Special Foundation for Transgenic Species of China (2014ZX0800605B), the Sichuan Science and Technology Program, China (2021YFYZ0009 and 2021YFYZ0030).
|About author: LONG Ke-ren, E-mail: firstname.lastname@example.org; LI Xiao-kai, E-mail: email@example.com; ZHANG Ruo-wei, E-mail: firstname.lastname@example.org; GU Yi-ren, E-mail: email@example.com; Correspondence LI Ming-zhou, E-mail: firstname.lastname@example.org; PAN Deng-ke, E-mail: email@example.com
* These authors contributed equally to this study.
Cite this article:
LONG Ke-ren, LI Xiao-kai, ZHANG Ruo-wei, GU Yi-ren, DU Min-jie, XING Xiang-yang, DU Jia-xiang, MAI Miao-miao, WANG Jing, JIN Long, TANG Qian-zi, HU Si-lu, MA Ji-deng, WANG Xun, PAN Deng-ke, LI Ming-zhou.
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, 21(9): 2675-2690.
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