The LXRB-SREBP1 network regulates lipogenic homeostasis by controlling the synthesis of polyunsaturated fatty acids in goat mammary epithelial cells
Abstract 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 m...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-11-01
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| Series: | Journal of Animal Science and Biotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40104-022-00774-4 |
| _version_ | 1811230258123243520 |
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| author | Wenying Zhang Changhui Zhang Jun Luo Huifen Xu Jianxin Liu Juan J. Loor Hengbo Shi |
| author_facet | Wenying Zhang Changhui Zhang Jun Luo Huifen Xu Jianxin Liu Juan J. Loor Hengbo Shi |
| author_sort | Wenying Zhang |
| collection | DOAJ |
| description | Abstract 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-CoA desaturase (SCD1) promoter. Results Overexpression of LXRB markedly upregulated the protein abundance of LXRB while incubation with siRNA 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 siLXRB and T09. The abundance of sterol regulatory element binding transcription factor 1 precursor (pSREBP1) and its mature fragment (nSREBP1) was upregulated by T09, but not LXRB overexpression. In the cells cultured with T09, knockdown of LXRB downregulated the abundance for pSREBP1 and nSREBP1. Luciferase reporter assays revealed that the activities of wild type SCD1 promoter or fragment with SREBP1 response element (SRE) mutation were decreased markedly when LXRB was knocked down. Activity of the SCD1 promoter that was induced by T09 was blocked when the SRE mutation was introduced. Conclusion The current study provides evidence of a physiological link between the LXRB and SREBP1 in the ruminant mammary cell. An important role was revealed for the LXRB-SREBP1 network in the synthesis of PUFA via the regulation of genes encoding elongases and desaturases. Thus, targeting this network might elicit broad effects on lipid homeostasis in ruminant mammary gland. |
| first_indexed | 2024-04-12T10:27:52Z |
| format | Article |
| id | doaj.art-296238a3445145549455fa735933deab |
| institution | Directory Open Access Journal |
| issn | 2049-1891 |
| language | English |
| last_indexed | 2024-04-12T10:27:52Z |
| publishDate | 2022-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Animal Science and Biotechnology |
| spelling | doaj.art-296238a3445145549455fa735933deab2022-12-22T03:36:56ZengBMCJournal of Animal Science and Biotechnology2049-18912022-11-0113111310.1186/s40104-022-00774-4The LXRB-SREBP1 network regulates lipogenic homeostasis by controlling the synthesis of polyunsaturated fatty acids in goat mammary epithelial cellsWenying Zhang0Changhui Zhang1Jun Luo2Huifen Xu3Jianxin Liu4Juan J. Loor5Hengbo Shi6Institute of Dairy Science, College of Animal Sciences, Zhejiang UniversityCollege of Animal Science and Technology, Northwest A&F UniversityCollege of Animal Science and Technology, Northwest A&F UniversityCollege of Animal Science and Technology, Henan Agricultural UniversityInstitute of Dairy Science, College of Animal Sciences, Zhejiang UniversityMammalian Nutrition Physiology Genomics, Department of Animal Sciences and Division of Nutritional Sciences, University of IllinoisInstitute of Dairy Science, College of Animal Sciences, Zhejiang UniversityAbstract 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-CoA desaturase (SCD1) promoter. Results Overexpression of LXRB markedly upregulated the protein abundance of LXRB while incubation with siRNA 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 siLXRB and T09. The abundance of sterol regulatory element binding transcription factor 1 precursor (pSREBP1) and its mature fragment (nSREBP1) was upregulated by T09, but not LXRB overexpression. In the cells cultured with T09, knockdown of LXRB downregulated the abundance for pSREBP1 and nSREBP1. Luciferase reporter assays revealed that the activities of wild type SCD1 promoter or fragment with SREBP1 response element (SRE) mutation were decreased markedly when LXRB was knocked down. Activity of the SCD1 promoter that was induced by T09 was blocked when the SRE mutation was introduced. Conclusion The current study provides evidence of a physiological link between the LXRB and SREBP1 in the ruminant mammary cell. An important role was revealed for the LXRB-SREBP1 network in the synthesis of PUFA via the regulation of genes encoding elongases and desaturases. Thus, targeting this network might elicit broad effects on lipid homeostasis in ruminant mammary gland.https://doi.org/10.1186/s40104-022-00774-4ElongaseLipid homeostasisLiver X receptor, Mammary glandPolyunsaturated fatty acids |
| spellingShingle | Wenying Zhang Changhui Zhang Jun Luo Huifen Xu Jianxin Liu Juan J. Loor Hengbo Shi The LXRB-SREBP1 network regulates lipogenic homeostasis by controlling the synthesis of polyunsaturated fatty acids in goat mammary epithelial cells Journal of Animal Science and Biotechnology Elongase Lipid homeostasis Liver X receptor, Mammary gland Polyunsaturated fatty acids |
| title | The LXRB-SREBP1 network regulates lipogenic homeostasis by controlling the synthesis of polyunsaturated fatty acids in goat mammary epithelial cells |
| title_full | The LXRB-SREBP1 network regulates lipogenic homeostasis by controlling the synthesis of polyunsaturated fatty acids in goat mammary epithelial cells |
| title_fullStr | The LXRB-SREBP1 network regulates lipogenic homeostasis by controlling the synthesis of polyunsaturated fatty acids in goat mammary epithelial cells |
| title_full_unstemmed | The LXRB-SREBP1 network regulates lipogenic homeostasis by controlling the synthesis of polyunsaturated fatty acids in goat mammary epithelial cells |
| title_short | The LXRB-SREBP1 network regulates lipogenic homeostasis by controlling the synthesis of polyunsaturated fatty acids in goat mammary epithelial cells |
| title_sort | lxrb srebp1 network regulates lipogenic homeostasis by controlling the synthesis of polyunsaturated fatty acids in goat mammary epithelial cells |
| topic | Elongase Lipid homeostasis Liver X receptor, Mammary gland Polyunsaturated fatty acids |
| url | https://doi.org/10.1186/s40104-022-00774-4 |
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