Knockdown of LXRα Inhibits Goat Intramuscular Preadipocyte Differentiation.
Knockdown of LXRα Inhibits Goat Intramuscular Preadipocyte Differentiation.
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LXRα 的敲低抑制山羊肌内前脂肪细胞分化
DOI：
10.3390/ijms19103037
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发表时间：
2018-10-05
影响因子：
5.6
通讯作者：
Zhu J
中科院分区：
文献类型：
--
作者：
Xiong Y;Xu Q;Lin S;Wang Y;Lin Y;Zhu J
山羊肌内脂肪（IMF）含量主要由肌内前脂肪细胞成脂分化和成熟脂肪细胞脂质积累过程决定。然而，这些生物过程的潜在调节因子在很大程度上仍然未知。在山羊肌内脂肪形成过程中，肝脏X受体α（LXRα）的表达在早期达到高峰，然后逐渐下降。由两个独立的siRNA介导的LXRα的敲低显著抑制肌内脂肪细胞脂质积聚并上调前脂肪细胞标志物-前脂肪细胞因子1（pref 1）表达。一致地，siRNA处理稳健地降低脂肪形成相关基因的mRNA水平，包括CCAAT增强子结合蛋白α（Cebpα）、过氧化物酶体增殖物激活受体γ（Pparg）、固醇调节元件结合蛋白同种型1c（Srebp 1c）、脂肪酸结合蛋白（aP 2）和脂蛋白脂肪酶（Lpl）。其次，腺病毒过表达LXRα不影响肌内脂肪细胞的脂肪生成，这通过油红O信号测量和脂肪生成特异性基因检测来证明。在机制上，我们发现CCAAT增强子结合蛋白β（Cebpβ）和Kruppel样因子8（Klf 8）都是LXRα的潜在靶点，这通过在这些基因的启动子处具有LXRα的推定结合位点以及与LXRα相比在脂肪形成期间的类似表达模式来指示。重要的是，Cebpβ和Klf 8的mRNA水平在山羊LXRα敲低肌内脂肪细胞中显著下调。这些结果表明，LXRα功能丧失可能通过下调Cebpβ和Klf 8抑制肌内脂肪形成。我们的研究将为山羊IMF沉积的机械调控提供新的见解。
Goat intramuscular fat (IMF) content is mainly determined by the processes of intramuscular preadipocytes adipogenic differentiation and mature adipocyte lipid accumulation. However, the underlying regulators of these biological processes remain largely unknown. Here, we report that the expression of Liver X receptor alpha (LXRα) reaches a peak at early stage and then gradually decreases during goat intramuscular adipogenesis. Knockdown of LXRα mediated by two independent siRNAs significantly inhibits intramuscular adipocytes lipid accumulation and upregulates preadipocytes marker- preadipocyte factor 1 (pref1) expression. Consistently, siRNA treatments robustly decrease mRNA level of adipogenic related genes, including CCAAT enhancer binding protein alpha (Cebpα), Peroxisome proliferator activated receptor gamma (Pparg), Sterol regulatory element binding protein isoform 1c (Srebp1c), Fatty acids binding protein (aP2) and Lipoprotein lipase (Lpl). Next, adenovirus overexpression of LXRα does not affect intramuscular adipocytes adipogenesis manifested by Oil Red O signal measurement and adipogenic specific genes detection. Mechanically, we found that both CCAAT enhancer binding protein beta (Cebpβ) and Kruppel like factor 8 (Klf8) are potential targets of LXRα, indicated by having putative binding sites of LXRα at the promoter of these genes and similar expression pattern during adipogenesis comparing to LXRα. Importantly, mRNA levels of Cebpβ and Klf8 are downregulated significantly in goat LXRα knockdown intramuscular adipocyte. These results demonstrate that loss function of LXRα inhibits intramuscular adipogenesis possibly through down-regulation of Cebpβ and Klf8. Our research will provide new insights into mechanical regulation of goat IMF deposition.