Liu Jiaqi, Li Jie, Chen Wentao, Xie Xintao, Chu Xingang, Valencak Teresa G, Wang Yizhen, Shan Tizhong
College of Animal Sciences, Zhejiang University, Hangzhou, China.
Key Laboratory of Molecular Animal Nutrition (Zhejiang University), Ministry of Education, Hangzhou, China.
J Anim Sci Biotechnol. 2021 Mar 3;12(1):19. doi: 10.1186/s40104-021-00546-6.
Meat quality is largely driven by fat deposition, which is regulated by several genes and signaling pathways. The cyclic adenosine monophosphate (cAMP) -regulated transcriptional coactivator 3 (CRTC3) is a coactivator of cAMP response element binding protein (CREB) that mediates the function of protein kinase A (PKA) signaling pathway and is involved in various biological processes including lipid and energy metabolism. However, the effects of CRTC3 on the metabolome and transcriptome of porcine subcutaneous adipocytes have not been studied yet. Here, we tested whether porcine CRTC3 expression would be related to fat deposition in Heigai pigs (a local fatty breed in China) and Duroc×Landrace×Yorkshire (DLY, a lean breed) pigs in vivo. The effects of adenovirus-induced CRTC3 overexpression on the metabolomic and transcriptomic profiles of subcutaneous adipocytes were also determined in vitro by performing mass spectrometry-based metabolomics combined with RNA sequencing (RNA-seq).
Porcine CRTC3 expression is associated with fat deposition in vivo. In addition, CRTC3 overexpression increased lipid accumulation and the expression of mature adipocyte-related genes in cultured porcine subcutaneous adipocytes. According to the metabolomic analysis, CRTC3 overexpression induced significant changes in adipocyte lipid, amino acid and nucleotide metabolites in vitro. The RNA-seq analysis suggested that CRTC3 overexpression alters the expression of genes and pathways involved in adipogenesis, fatty acid metabolism and glycerophospholipid metabolism in vitro.
We identified significant alterations in the metabolite composition and the expression of genes and pathways involved in lipid metabolism in CRTC3-overexpressing adipocytes. Our results suggest that CRTC3 might play an important regulatory role in lipid metabolism and thus affects lipid accumulation in porcine subcutaneous adipocytes.
肉质很大程度上受脂肪沉积驱动,而脂肪沉积受多个基因和信号通路调控。环磷酸腺苷(cAMP)调节的转录共激活因子3(CRTC3)是cAMP反应元件结合蛋白(CREB)的共激活因子,介导蛋白激酶A(PKA)信号通路的功能,并参与包括脂质和能量代谢在内的各种生物学过程。然而,CRTC3对猪皮下脂肪细胞代谢组和转录组的影响尚未得到研究。在此,我们测试了猪CRTC3的表达是否与中国地方脂肪型品种黑盖猪和瘦肉型品种杜洛克×长白×大白(DLY)猪体内的脂肪沉积有关。还通过基于质谱的代谢组学结合RNA测序(RNA-seq)在体外确定了腺病毒诱导的CRTC3过表达对皮下脂肪细胞代谢组和转录组图谱的影响。
猪CRTC3的表达与体内脂肪沉积有关。此外,CRTC3过表达增加了培养的猪皮下脂肪细胞中的脂质积累以及成熟脂肪细胞相关基因的表达。根据代谢组学分析,CRTC3过表达在体外诱导了脂肪细胞脂质、氨基酸和核苷酸代谢物的显著变化。RNA-seq分析表明,CRTC3过表达在体外改变了参与脂肪生成、脂肪酸代谢和甘油磷脂代谢的基因和通路的表达。
我们在CRTC3过表达的脂肪细胞中发现了代谢物组成以及参与脂质代谢的基因和通路表达的显著变化。我们的结果表明,CRTC3可能在脂质代谢中发挥重要的调节作用,从而影响猪皮下脂肪细胞中的脂质积累。