Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling, Xianyang 712100, China.
Int J Mol Sci. 2024 Oct 21;25(20):11318. doi: 10.3390/ijms252011318.
Goat milk is abundant in nutrients, particularly in milk fats, which confer health benefits to humans. Exploring the regulatory mechanism of fatty acid synthesis is highly important to understand milk composition manipulation. In this study, we used chromatin immunoprecipitation sequencing (ChIP-seq) on goat mammary glands at different lactation stages which revealed a novel lactation regulatory factor: cell death-inducing DFFA-like effector B (CIDEB). RT-qPCR results revealed that CIDEB was significantly upregulated during lactation in dairy goats. CIDEB overexpression significantly increased the expression levels of genes involved in fatty acid synthesis (, , < 0.05; , < 0.01), lipid droplet formation (, < 0.05), and triacylglycerol (TAG) synthesis (, < 0.05; , < 0.01) in goat mammary epithelial cells (GMECs). The contents of lipid droplets, TAG, and cholesterol were increased ( < 0.05) in CIDEB-overexpressing GMECs, and knockdown of CIDEB led to the opposite results. In addition, CIDEB knockdown significantly decreased the proportion of C16:0 and total C18:2. Luciferase reporter assays indicated that X-box binding protein 1 (XBP1) promoted CIDEB transcription via XBP1 binding sites located in the CIDEB promoter. Furthermore, CIDEB knockdown attenuated the stimulatory effect of XBP1 on lipid droplet accumulation. Collectively, these findings elucidate the critical regulatory roles of CIDEB in milk fat synthesis, thus providing new insights into improving the quality of goat milk.
羊奶富含营养物质，特别是在乳脂肪中，这些物质对人类健康有益。探索脂肪酸合成的调控机制对于理解乳成分的调控非常重要。在本研究中，我们使用了不同泌乳阶段山羊乳腺的染色质免疫沉淀测序（ChIP-seq），揭示了一种新的泌乳调节因子：细胞死亡诱导型 DFFA 样效应因子 B（CIDEB）。RT-qPCR 结果显示，CIDEB 在乳用山羊泌乳期显著上调。CIDEB 过表达显著增加了参与脂肪酸合成的基因的表达水平（ 、 、 < 0.05； 、 < 0.01）、脂滴形成（ 、 < 0.05）和三酰基甘油（TAG）合成（ 、 < 0.05； 、 < 0.01）在山羊乳腺上皮细胞（GMEC）中。CIDEB 过表达 GMECs 中的脂滴、TAG 和胆固醇含量增加（ < 0.05），而 CIDEB 敲低则导致相反的结果。此外，CIDEB 敲低显著降低了 C16:0 和总 C18:2 的比例。荧光素酶报告基因测定表明，X 盒结合蛋白 1（XBP1）通过位于 CIDEB 启动子中的 XBP1 结合位点促进 CIDEB 转录。此外，CIDEB 敲低减弱了 XBP1 对脂滴积累的刺激作用。综上所述，这些发现阐明了 CIDEB 在乳脂合成中的关键调节作用，为提高羊奶质量提供了新的见解。
