鉴定新型反义长链非编码RNA APMAP-AS调节猪脂肪生成分化和炎症反应

doi:10.1016/j.jia.2022.11.005

摘要/Abstract

摘要：

脂肪沉积是猪最重要的经济性状之一，是猪遗传学研究和育种工作中关注的焦点，其分子调控机制一直被视为猪分子育种重要研究内容。猪的生理结构、器官大小、代谢特征以及脂肪的生理解剖位置与人类更为相似，脂肪易沉积、易解剖和易获取，这使得猪成为研究不同内脏脂肪组织结构与功能的理想选择。长链非编码RNA (long non-coding RNA, lncRNA)是一类具有重要基因调控功能的RNA分子，在多种生物学过程中起着重要作用。随着对lncRNAs研究的深入，人们发现它不仅影响脂肪细胞的合成，还对脂肪过度沉积伴随的肥胖和代谢综合征相关的全身低度炎症具有调节作用。然而，lncRNAs对猪的内脏脂肪组织沉积过程中的调控作用还有待进行进一步研究。因此，本研究以成年雌性巴马猪（2年）为研究对象，分两组进行基础饮食和高脂饮食饲喂后，通过转录组测序技术对两组个体的内脏脂肪（腹膜后脂肪）进行测序。通过分析两组样本的测序数据，筛选了差异表达的lncRNAs，在细胞水平上进行lncRNAs的功能验证。在这里，我们在猪的基因组中发现了一个新的反义转录物，命名为APMAP-AS，由脂肪细胞膜相关蛋白（APMAP）转录而成。与对照组猪相比，APMAP-AS和APMAP在肥胖猪的腹膜后脂肪中高度表达。利用猪骨髓间质干细胞的脂肪分化模型，我们发现APMAP-AS对脂肪形成成分化有积极的调节作用。同时，APMAP-AS促进了脂质代谢并抑制了炎症因子的表达。APMAP-AS有可能与APMAP形成一个RNA-RNA双链，并增加APMAP mRNA的稳定性，从而起到正向调控猪体内APMAP表达的作用。这些结果表明，APMAP-AS通过顺式作用调节APMAP基因的表达，从而影响脂肪沉积、脂质代谢和巴马猪腹膜后脂肪组织的免疫反应。APMAP-AS是一种适应性机制，在肥胖期间促进脂肪组织的健康重塑并维持代谢平衡。这些与脂质合成相关的调控基因的天然反义转录物的发现，可能会进一步加深我们对lncRNAs在驱动适应性脂肪组织重塑和维护代谢健康方面的理解。

Abstract: Long non-coding RNAs (lncRNAs) are emerging as powerful regulators of adipocyte differentiation, fat metabolism and gene expression. However, the functional roles and mechanisms of lncRNAs in these processes remain unclear. Here, we identified a novel antisense transcript, named APMAP-AS, transcribed from adipocyte membrane-associated protein (APMAP) in the pig genome. APMAP-AS and APMAP were highly expressed in retroperitoneal adipose of obese pigs, compared with that in control pigs. Using a bone mesenchymal stem cells (BMSCs) adipogenic differentiation model, we found that APMAP-AS positively regulated adipogenic differentiation. APMAP-AS had the potential to form an RNA–RNA duplex with APMAP, and increased the stability of APMAP mRNA. Additionally, APMAP-AS promoted lipid metabolism and inhibited the expression of inflammatory factors. These findings of a natural antisense transcript for a regulatory gene associated with lipid synthesis might further our understanding of lncRNAs in driving adaptive adipose tissue remodeling and preserving metabolic health.

Key words: lncRNA , adipogenesis , lipid metabolism , inflammation , RNA–RNA duplex

ZHANG Lin-zhen, HE Li, WANG Ning, AN Jia-hua, ZHANG Gen, CHAI Jin, WU Yu-jie, DAI Chang-jiu, LI Xiao-han, LIAN Ting, LI Ming-zhou, JIN Long. 鉴定新型反义长链非编码RNA APMAP-AS调节猪脂肪生成分化和炎症反应[J]. Journal of Integrative Agriculture, 2023, 22(8): 2483-2499.

ZHANG Lin-zhen, HE Li, WANG Ning, AN Jia-hua, ZHANG Gen, CHAI Jin, WU Yu-jie, DAI Chang-jiu, LI Xiao-han, LIAN Ting, LI Ming-zhou, JIN Long. Identification of novel antisense long non-coding RNA APMAP-AS that modulates porcine adipogenic differentiation and inflammatory responses[J]. Journal of Integrative Agriculture, 2023, 22(8): 2483-2499.

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