College of Life Science and Technology, Southwest Minzu University, Chengdu 610041, China.
Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Ministry of Education, Southwest Minzu University, Chengdu 610041, China.
Int J Mol Sci. 2018 Oct 5;19(10):3037. doi: 10.3390/ijms19103037.
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 () 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 () expression. Consistently, siRNA treatments robustly decrease mRNA level of adipogenic related genes, including CCAAT enhancer binding protein alpha (), Peroxisome proliferator activated receptor gamma (), Sterol regulatory element binding protein isoform 1c (), Fatty acids binding protein () and Lipoprotein lipase (). 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 () and Kruppel like factor 8 () 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 and 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 and . Our research will provide new insights into mechanical regulation of goat IMF deposition.
山羊肌内脂肪(IMF)含量主要取决于肌内前体脂肪细胞的脂肪生成分化和成熟脂肪细胞的脂质积累过程。然而,这些生物学过程的潜在调节因子在很大程度上仍然未知。在这里,我们报告说,肝 X 受体α(LXRα)的表达在山羊肌内脂肪生成早期达到峰值,然后逐渐降低。两种独立的 siRNA 介导的 LXRα 敲低显著抑制肌内脂肪细胞的脂质积累,并上调前体脂肪细胞标志物-前脂肪细胞因子 1(Pref-1)的表达。一致地,siRNA 处理显著降低了脂肪生成相关基因的 mRNA 水平,包括 CCAAT 增强子结合蛋白α(C/EBPα)、过氧化物酶体增殖物激活受体γ(PPARγ)、固醇调节元件结合蛋白 1c(SREBP1c)、脂肪酸结合蛋白(FABP)和脂蛋白脂肪酶(LPL)。接下来,腺病毒过表达 LXRα 不会影响肌内脂肪细胞的脂肪生成,表现为油红 O 信号测量和脂肪生成特异性基因检测。机械地,我们发现 CCAAT 增强子结合蛋白β(C/EBPβ)和 Kruppel 样因子 8(KLF8)都是 LXRα 的潜在靶点,这些基因的启动子中存在 LXRα 的潜在结合位点,并且在脂肪生成过程中的表达模式与 LXRα 相似。重要的是,在山羊 LXRα 敲低的肌内脂肪细胞中,和的 mRNA 水平显著下调。这些结果表明,LXRα 的功能丧失可能通过下调和来抑制肌内脂肪生成。我们的研究将为山羊 IMF 沉积的机械调节提供新的见解。