The LXRB-SREBP1 network regulates lipogenic homeostasis by controlling the synthesis of polyunsaturated fatty acids in goat mammary epithelial cells  

作　　者：Wenying Zhang Changhui Zhang Jun Luo Huifen Xu Jianxin Liu Juan JLoor Hengbo Shi 

机构地区：[1]Institute of Dairy Science,College of Animal Sciences,Zhejiang University,Hangzhou 310058,China [2]College of Animal Science and Technology,Northwest A&F University,Yangling 712100,China [3]College of Animal Science and Technology,Henan Agricultural University,Zhengzhou 450046,China [4]Key Laboratory of Molecular Animal Nutrition(Zhejiang University),Ministry of Education,Hangzhou,310058,China [5]Mammalian Nutrition Physiology Genomics,Department of Animal Sciences and Division of Nutritional Sciences,University of Illinois,Urbana,IL 61801,USA.

出　　处：《Journal of Animal Science and Biotechnology》2023年第2期614-626,共13页畜牧与生物技术杂志（英文版）

基　　金：supported by the National Natural Science Foundation of China(31702090);Key R&D program of Zhejiang Province(2022C04017);Zhejiang Provincial Major Science and Technology Projects on Agricultural New Varieties Selection and Breeding(2021C02068-6);Opening fund in Key Laboratory of Molecular Animal Nutrition(Zhejiang University,KLMAN202103).

摘　　要：Background:In rodents,research has revealed a role of liver X receptors(LXR) in controlling lipid homeostasis and regulating the synthesis of polyunsaturated fatty acids(PUFA).Recent data suggest that LXRB is the predominant LXR subtype in ruminant mammary cells,but its role in lipid metabolism is unknown.It was hypothesized that LXRB plays a role in lipid homeostasis via altering the synthesis of PUFA in the ruminant mammary gland.We used overexpression and knockdown of LXRB in goat primary mammary epithelial cells(GMEC) to evaluate abundance of lipogenic enzymes,fatty acid profiles,content of lipid stores and activity of the stearoyl-Co A desaturase(SCD1) promoter.Results:Overexpression of LXRB markedly upregulated the protein abundance of LXRB while incubation with si RNA targeting LXRB markedly decreased abundance of LXRB protein.Overexpression of LXRB plus T0901317(T09,a ligand for LXR) dramatically upregulated SCD1 and elongation of very long chain fatty acid-like fatty acid elongases 5–7(ELOVL 5–7),which are related to PUFA synthesis.Compared with the control,cells overexpressing LXRB and stimulated with T09 had greater concentrations of C16:0,16:1,18:1n7,18:1n9 and C18:2 as well as desaturation and elongation indices of C16:0.Furthermore,LXRB-overexpressing cells incubated with T09 had greater levels of triacylglycerol and cholesterol.Knockdown of LXRB in cells incubated with T09 led to downregulation of genes encoding elongases and desaturases.Knockdown of LXRB attenuated the increase in triacylglycerol and cholesterol that was induced by T09.In cells treated with dimethylsulfoxide,knockdown of LXRB increased the concentration of C16:0 at the expense of C18:0,while a significant decrease in C18:2 was observed in cells incubated with both si LXRB and T09.The abundance of sterol regulatory element binding transcription factor 1 precursor(p SREBP1) and its mature fragment(n SREBP1) was upregulated by T09,but not LXRB overexpression.In the cells cultured with T09,knockdown of LXRB downregulated the abund

关 键 词：ELONGASE Lipid homeostasis Liver X receptor Mammary gland Polyunsaturated fatty acids 

分 类 号：S858[农业科学—临床兽医学]