Reconstitution of UCP1 using CRISPR/Cas9 in the white adipose tissue of pigs decreases fat deposition and improves thermogenic capacity

Authors: Qiantao Zheng, Jun Lin, Jiaojiao Huang, Hongyong Zhang, Rui Zhang, Xueying Zhang, Chunwei Cao, Catherine Hambly, Guosong Qin, Jing Yao, Ruigao Song, Qitao Jia, Xiao Wang, Yongshun Li, Nan Zhang, Zhengyu Piao, Rongcai Ye, John R. Speakman, Hongmei Wang, Qi Zhou, Yanfang Wang, Wanzhu Jin, Jianguo Zhao - Proceedings of the National Academy of Sciences, PNAS 2017 cited by 201

Significance Uncoupling protein 1 (UCP1) is responsible for brown adipose tissue-mediated thermogenesis and plays a critical role in protecting against cold and regulating energy homeostasis. Modern pigs lack functional UCP1, which makes them susceptible to cold and prone to fat deposition and results in neonatal mortality and decreased production efficiency. In the current study, a CRISPR/Cas9-mediated homologous recombination-independent approach was established, and mouse adiponectin-UCP1 was efficiently inserted into the porcine endogenous UCP1 locus. The resultant UCP1 KI pigs showed an improved ability to maintain body temperature, decreased fat deposition, and increased carcass lean percentage. UCP1 KI pigs are a potentially valuable resource for the pig industry that can improve pig welfare and reduce economic losses.