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

文献类型： 外文期刊

第一作者： Zheng, Qiantao

作者： Zheng, Qiantao;Huang, Jiaojiao;Zhang, Hongyong;Zhang, Rui;Cao, Chunwei;Qin, Guosong;Yao, Jing;Song, Ruigao;Jia, Qitao;Wang, Xiao;Li, Yongshun;Zhang, Nan;Wang, Hongmei;Zhou, Qi;Zhao, Jianguo;Zheng, Qiantao;Huang, Jiaojiao;Zhang, Hongyong;Zhang, Rui;Cao, Chunwei;Qin, Guosong;Yao, Jing;Song, Ruigao;Jia, Qitao;Wang, Xiao;Wang, Hongmei;Zhou, Qi;Jin, Wanzhu;Zhao, Jianguo;Lin, Jun;Song, Ruigao;Ye, Rongcai;Jin, Wanzhu;Lin, Jun;Ye, Rongcai;Zhang, Xueying;Speakman, John R.;Hambly, Catherine;Speakman, John R.;Piao, Zhengyu;Wang, Yanfang

作者机构：

关键词： UCP1;thermoregulation;fat deposition;pig;CRISPR/Cas9

期刊名称：PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA （ 影响因子：11.205； 五年影响因子：12.291 ）

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收录情况： SCI

摘要： Uncoupling protein 1 (UCP1) is localized on the inner mitochondrial membrane and generates heat by uncoupling ATP synthesis from proton transit across the inner membrane. UCP1 is a key element of nonshivering thermogenesis and is most likely important in the regulation of body adiposity. Pigs (Artiodactyl family Suidae) lack a functional UCP1 gene, resulting in poor thermoregulation and susceptibility to cold, which is an economic and pig welfare issue owing to neonatal mortality. Pigs also have a tendency toward fat accumulation, which may be linked to their lack of UCP1, and thus influences the efficiency of pig production. Here, we report application of a CRISPR/Cas9-mediated, homologous recombination (HR)-independent approach to efficiently insert mouse adiponectin-UCP1 into the porcine endogenous UCP1 locus. The resultant UCP1 knock-in (KI) pigs showed an improved ability to maintain body temperature during acute cold exposure, but they did not have alterations in physical activity levels or total daily energy expenditure (DEE). Furthermore, ectopic UCP1 expression in white adipose tissue (WAT) dramatically decreased fat deposition by 4.89% (P < 0.01), consequently increasing carcass lean percentage (CLP; P < 0.05). Mechanism studies indicated that the loss of fat upon UCP1 activation in WAT was linked to elevated lipolysis. UCP1 KI pigs are a potentially valuable resource for agricultural production through their combination of cold adaptation, which improves pig welfare and reduces economic losses, with reduced fat deposition and increased lean meat production.

分类号： N

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