论文
论文题目: Reconstitution of UCP1 Using CRISPR/Cas9 in the White Adipose Tissue of Pigs Decreases Fat Deposition and Improves Thermogenic Capacity
论文题目英文:
作者: 郑千涛①,林骏①,黄娇娇①,张洪勇,张蕊,#Xue-Ying Zhang,曹春伟,#Catherine Hambly,秦国嵩,姚婧,宋瑞高,贾启涛,王霄,Yong-Shun Li,张楠,#Zheng-Yu Piao,叶荣财,#John R. Speakman,王红梅,周琪,#王彦芳*,金万洙*,赵建国*
论文出处:
年: 2017
卷:
期: DOI: 10.1073/pnas.1707853114
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联系作者: #王彦芳,金万洙,赵建国
发表期刊: Proceedings of the National Academy of Sciences
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论文连接 http://www.pnas.org/content/early/2017/10/17/1707853114.abstract?sid=d35f10ff-d88e-4e59-98f3-e87e8506643e
影响因子:
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.
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