Adipose lipidomics and RNA-Seq analysis revealed the enhanced mitochondrial function in UCP1 knock-in pigs
Adipose lipidomics and RNA-Seq analysis revealed the enhanced mitochondrial function in UCP1 knock-in pigs
复制标题
脂肪脂质组学和 RNA-Seq 分析揭示 UCP1 敲入猪的线粒体功能增强
DOI：
10.1016/j.bbalip.2019.06.017
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发表时间：
2019-10-01
影响因子：
4.8
通讯作者：
Wang, Yanfang
中科院分区：
文献类型：
--
作者：
Pan, Jianfei;Tao, Cong;Wang, Yanfang
解偶联蛋白1（UCP 1）在非颤抖性产热中起关键作用，并参与肥胖的发病机制。在以前的研究中，我们产生了脂肪细胞特异性UCP 1基因敲入（UCP 1-KI）猪，表现出改善的体温调节能力和减少脂肪沉积。为了研究UCP 1基因敲入是否改变脂肪组织的脂质组成，对来自6月龄冷处理UCP 1-KI猪和野生型（WT）猪的腹股沟皮下白色脂肪组织（iWAT）和背膘的脂质组学进行了分析。此外，进行iWAT的全基因组RNA测序以进一步研究脂质改变的遗传基础。结果表明，来自UCP 1-KI猪的iWAT和背膘表现出不同的脂质组学特征，因为在UCP 1基因敲入猪的背膘中观察到轻度脂质改变。来自UCP 1-KI猪的腹股沟WAT含有显著降低的总三酰甘油（p < 0.05），以及参与脂肪酸代谢的基因的下调，表明UCP 1-KI猪的iWAT中脂肪生成降低。在UCP 1-KI猪的iWAT中也观察到总鞘脂水平显著增加（p < 0.05）。值得注意的是，发现在来自UCP 1-KI猪的iWAT中，两种脑特异性脂质种类心磷脂CL 72：8（18：2）和CL 74：9（18：2）显著增加，表明线粒体功能增强。这一观察结果进一步得到了UCPI-KI猪iWAT中大量线粒体相关基因的显著上调和大线粒体和线粒体嵴数量的显著增加的支持。综上所述，这些数据说明了UCPI在猪脂肪组织脂质代谢中的特定作用，并为UCP 1-KI猪脂肪性状的表征提供了新的数据。
Uncoupling protein 1 (UCP1) plays a key role in nonshivering thermogenesis and is involved in the pathogenesis of obesity. In a previous study, we generated adipocyte-specific UCP1 knock-in (UCP1-KI) pigs, which exhibited improved thermoregulatory ability and decreased fat deposition. To investigate whether UCP1 knock-in alters the lipid composition of adipose tissues, lipidomics of inguinal subcutaneous white adipose tissue (iWAT) and backfat from 6-month-old cold-treated UCP1-KI pigs and wild-type (WT) pigs were profiled. In addition, genomewide RNA-sequencing of iWAT was performed to further study the genetic basis for lipid alterations. The results showed that iWAT and backfat from UCP1-KI pigs exhibited distinct lipidomic profiles, as the mild lipid alteration was observed in backfat of UCP1 knock-in pigs. Inguinal WAT from UCP1-KI pigs contained significantly decreased total triacylglycerol (p < 0.05), together with the downregulation of genes involved in fatty acid metabolism, suggesting the decreased lipogenesis in iWAT of UCP1-KI pigs. Significantly increased levels of total sphingolipids (p < 0.05) were also observed in iWAT from UCP1-KI pigs. Notably, two mitochondrial-specific lipid species, cardiolipin CL72:8 (18:2) and CL74:9 (18:2), were found to be dramatically increased in iWAT from UCP1-KI pigs, suggesting enhanced mitochondria] function. This observation was further supported by the significant upregulation of numerous mitochondrial-related genes and significantly increased number of large mitochondria and mitochondria] cristae in iWAT of UCPI-KI pigs. Taken together, these data illustrate the specific role of UCPI in lipid metabolism of fat tissues in pigs and provide new data for characterization of fat traits in UCP1-KI pigs.