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FoxO1 Knockdown Promotes Fatty Acid Synthesis via Modulating SREBP1 Activities in the Dairy Goat Mammary Epithelial Cells
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2020-10-15 , DOI: 10.1021/acs.jafc.0c05237
Qiuya He 1 , Jun Luo 1 , Jiao Wu 1 , Weiwei Yao 1 , Zhuang Li 1 , Hui Wang 2 , Huifen Xu 3
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2020-10-15 , DOI: 10.1021/acs.jafc.0c05237
Qiuya He 1 , Jun Luo 1 , Jiao Wu 1 , Weiwei Yao 1 , Zhuang Li 1 , Hui Wang 2 , Huifen Xu 3
Affiliation
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FoxO1 is a crucial transcription factor involved in lipid metabolism in mouse liver through repressing a key regulator of lipogenesis, sterol regulatory element binding protein 1 (SREBP1). However, it remains elusive whether FoxO1 plays roles in the regulation of fatty acid metabolism during lactation in dairy goats. In this study, we aim to investigate the function of FoxO1 in goat mammary epithelial cells (GMECs). We found that the expression of FoxO1 is significantly upregulated during lactation compared with the dry period. FoxO1 knockdown enhanced the expression of genes related to de novo fatty acid synthesis (e.g., FASN, ELOVL6 and SCD1) and triacylglycerol (TAG) synthesis (e.g., DGAT2 and GPAM). Consistently, intracellular TAG was significantly increased in FoxO1 knockdown cells and reduced in FoxO1 overexpression cells. Immunofluorescence staining revealed that insulin suppresses FoxO1 transcription by promoting its nuclear export. Further, we found that FoxO1 inhibits insulin-induced SREBP1 promoter activities in GMECs. Moreover, FoxO1 suppresses SREBP1 transcription via the LXR response element (LXRE) and SREBP response element (SRE) located in the SREBP1 promoter. Our data reveal that FoxO1 plays critical roles in regulating the synthesis of the fatty acid and triacylglycerol (TAG) in GMECs.
中文翻译:
FoxO1组合式通过调节乳山羊乳腺上皮细胞中的SREBP1活性促进脂肪酸合成。
FoxO1是通过抑制脂肪形成的关键调节剂,即固醇调节元件结合蛋白1(SREBP1),参与小鼠肝脏脂质代谢的关键转录因子。然而,在奶山羊泌乳期间FoxO1是否在脂肪酸代谢的调节中起着作用尚不清楚。在这项研究中,我们旨在调查FoxO1在山羊乳腺上皮细胞(GMECs)中的功能。我们发现与干乳期相比,哺乳期FoxO1的表达明显上调。FoxO1组合式增强了与从头脂肪酸合成相关的基因(例如,FASN,ELOVL6和SCD1)和三酰基甘油(TAG)合成(例如,DGAT2)的基因的表达和GPAM)。一致地,在FoxO1敲低细胞中细胞内TAG显着增加,而在FoxO1过表达细胞中则减少。免疫荧光染色表明,胰岛素通过促进其核输出来抑制FoxO1转录。此外,我们发现FoxO1抑制GMEC中胰岛素诱导的SREBP1启动子活性。此外,FoxO1的禁止显示SREBP1通过位于所述LXR反应元件(LXRE)和SREBP应答元件(SRE)的转录SREBP1启动子。我们的数据表明,FoxO1在调节GMEC中脂肪酸和三酰甘油(TAG)的合成中起关键作用。
更新日期:2020-10-29
中文翻译:

FoxO1组合式通过调节乳山羊乳腺上皮细胞中的SREBP1活性促进脂肪酸合成。
FoxO1是通过抑制脂肪形成的关键调节剂,即固醇调节元件结合蛋白1(SREBP1),参与小鼠肝脏脂质代谢的关键转录因子。然而,在奶山羊泌乳期间FoxO1是否在脂肪酸代谢的调节中起着作用尚不清楚。在这项研究中,我们旨在调查FoxO1在山羊乳腺上皮细胞(GMECs)中的功能。我们发现与干乳期相比,哺乳期FoxO1的表达明显上调。FoxO1组合式增强了与从头脂肪酸合成相关的基因(例如,FASN,ELOVL6和SCD1)和三酰基甘油(TAG)合成(例如,DGAT2)的基因的表达和GPAM)。一致地,在FoxO1敲低细胞中细胞内TAG显着增加,而在FoxO1过表达细胞中则减少。免疫荧光染色表明,胰岛素通过促进其核输出来抑制FoxO1转录。此外,我们发现FoxO1抑制GMEC中胰岛素诱导的SREBP1启动子活性。此外,FoxO1的禁止显示SREBP1通过位于所述LXR反应元件(LXRE)和SREBP应答元件(SRE)的转录SREBP1启动子。我们的数据表明,FoxO1在调节GMEC中脂肪酸和三酰甘油(TAG)的合成中起关键作用。