PDF(Pubmed)
Abstract：
UNASSIGNED: The COBLL1 gene has been implicated in human central obesity, fasting insulin levels, type 2 diabetes, and blood lipid profiles. However, its molecular mechanisms remain largely unexplored.
UNASSIGNED: In this study, we established cobll1a mutant lines using the CRISPR/Cas9-mediated gene knockout technique. To further dissect the molecular underpinnings of cobll1a during early development, transcriptome sequencing and bioinformatics analysis was employed.
UNASSIGNED: Our study showed that compared to the control, cobll1a -/- zebrafish embryos exhibited impaired development of digestive organs, including the liver, intestine, and pancreas, at 4 days post-fertilization (dpf). Transcriptome sequencing and bioinformatics analysis results showed that in cobll1a knockout group, the expression level of genes in the Retinoic Acid (RA) signaling pathway was affected, and the expression level of lipid metabolism-related genes (fasn, scd, elovl2, elovl6, dgat1a, srebf1 and srebf2) were significantly changed (p < 0.01), leading to increased lipid synthesis and decreased lipid catabolism. The expression level of apolipoprotein genes (apoa1a, apoa1b, apoa2, apoa4a, apoa4b, and apoea) genes were downregulated.
UNASSIGNED: Our study suggest that the loss of cobll1a resulted in disrupted RA metabolism, reduced lipoprotein expression, and abnormal lipid transport, therefore contributing to lipid accumulation and deleterious effects on early liver development.
UNASSIGNED: In this study, we established cobll1a mutant lines using the CRISPR/Cas9-mediated gene knockout technique. To further dissect the molecular underpinnings of cobll1a during early development, transcriptome sequencing and bioinformatics analysis was employed.
UNASSIGNED: Our study showed that compared to the control, cobll1a -/- zebrafish embryos exhibited impaired development of digestive organs, including the liver, intestine, and pancreas, at 4 days post-fertilization (dpf). Transcriptome sequencing and bioinformatics analysis results showed that in cobll1a knockout group, the expression level of genes in the Retinoic Acid (RA) signaling pathway was affected, and the expression level of lipid metabolism-related genes (fasn, scd, elovl2, elovl6, dgat1a, srebf1 and srebf2) were significantly changed (p < 0.01), leading to increased lipid synthesis and decreased lipid catabolism. The expression level of apolipoprotein genes (apoa1a, apoa1b, apoa2, apoa4a, apoa4b, and apoea) genes were downregulated.
UNASSIGNED: Our study suggest that the loss of cobll1a resulted in disrupted RA metabolism, reduced lipoprotein expression, and abnormal lipid transport, therefore contributing to lipid accumulation and deleterious effects on early liver development.
摘要：
■COBLL1基因与人类中心性肥胖有关，空腹胰岛素水平，2型糖尿病,和血脂概况。然而,其分子机制在很大程度上仍未被探索。
■在这项研究中，我们使用CRISPR/Cas9介导的基因敲除技术建立了cobll1a突变系.为了在早期开发过程中进一步剖析cobll1a的分子基础，采用转录组测序和生物信息学分析。
■我们的研究表明，与对照组相比，cobll1a-/-斑马鱼胚胎表现出消化器官发育受损，包括肝脏,肠,还有胰腺,在受精后4天（dpf）。转录组测序和生物信息学分析结果表明,在cobll1a基因敲除组中,视黄酸(RA)信号通路基因的表达水平受到影响,和脂质代谢相关基因的表达水平(fasn，scd,elovl2,elovl6,dgat1a,srebf1和srebf2)发生显著变化(p<0.01)，导致脂质合成增加和脂质分解代谢减少。载脂蛋白基因的表达水平（apoa1a，apoa1b,apoa2,apoa4a,apoa4b,和apoea）基因下调。
■我们的研究表明，cobll1a的丢失导致RA代谢中断，脂蛋白表达减少，和异常的脂质运输，因此有助于脂质积累和对早期肝脏发育的有害影响。
■在这项研究中，我们使用CRISPR/Cas9介导的基因敲除技术建立了cobll1a突变系.为了在早期开发过程中进一步剖析cobll1a的分子基础，采用转录组测序和生物信息学分析。
■我们的研究表明，与对照组相比，cobll1a-/-斑马鱼胚胎表现出消化器官发育受损，包括肝脏,肠,还有胰腺,在受精后4天（dpf）。转录组测序和生物信息学分析结果表明,在cobll1a基因敲除组中,视黄酸(RA)信号通路基因的表达水平受到影响,和脂质代谢相关基因的表达水平(fasn，scd,elovl2,elovl6,dgat1a,srebf1和srebf2)发生显著变化(p<0.01)，导致脂质合成增加和脂质分解代谢减少。载脂蛋白基因的表达水平（apoa1a，apoa1b,apoa2,apoa4a,apoa4b,和apoea）基因下调。
■我们的研究表明，cobll1a的丢失导致RA代谢中断，脂蛋白表达减少，和异常的脂质运输，因此有助于脂质积累和对早期肝脏发育的有害影响。
