Acyl‐CoA synthetase short‐chain family member 2 (ACSS2) is regulated by SREBP‐1 and plays a role in fatty acid synthesis in caprine mammary epithelial cells
| Autor: | Ming Li, Gongzhen Ma, Juan J. Loor, Huifen Xu, Jun Luo, Xueying Zhang, Dawei Yao |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
ATP citrate lyase Physiology Coenzyme A Clinical Biochemistry Acetate-CoA Ligase Transfection Gene Expression Regulation Enzymologic 03 medical and health sciences chemistry.chemical_compound Mammary Glands Animal 0302 clinical medicine Lipid droplet ACSS2 Animals Lactation Promoter Regions Genetic Cells Cultured Triglycerides Fatty acid synthesis chemistry.chemical_classification Goats Lipogenesis Fatty Acids Fatty acid Epithelial Cells Lipid Droplets Cell Biology Serum Response Element 030104 developmental biology Biochemistry chemistry 030220 oncology & carcinogenesis Mutation ATP Citrate (pro-S)-Lyase Mutagenesis Site-Directed Sterol Regulatory Element Binding Protein 1 Female RNA Interference lipids (amino acids peptides and proteins) |
| Zdroj: | Journal of Cellular Physiology. 233:1005-1016 |
| ISSN: | 1097-4652 0021-9541 |
| Popis: | Sterol regulatory element binding protein 1 (SREBP-1) is well-known as the master regulator of lipogenesis in rodents. Acyl-CoA synthetase short-chain family member 2 (ACSS2) plays a key role in lipogenesis by synthesizing acetyl-CoA from acetate for lipogenesis. ATP citrate lyase (ACLY) catalyzes the conversion of citrate and coenzyme A to acetyl-CoA, hence, it is also important for lipogenesis. Although ACSS2 function in cancer cells has been elucidated, its essentiality in ruminant mammary lipogenesis is unknown. Furthermore, ACSS2 gene promoter and its regulatory mechanisms have not known. Expression of ACSS2 was high in lipid synthesizing tissues, and its expression increased during lactation compared with non-lactating period. Simultaneous knockdown of both ACSS2 and ACLY by siRNA in primary goat mammary epithelial cells decreased (p < 0.05) the mRNA abundance of genes associated with de novo fatty acid synthesis (FASN, ACACA, SCD1) and triacylglycerol (TAG) synthesis (DGAT1, DGAT2, GPAM, and AGPAT6). Genes responsible for lipid droplet formation and secretion (PLIN2 and PLIN3) and fatty acid oxidation (ATGL, HSL, ACOX, and CPT1A) all decreased (p < 0.05) after ACSS2 and ACLY knockdown. Total cellular TAG content and lipid droplet formation also decreased. Use of a luciferase reporter assay revealed a direct regulation of ACSS2 by SREBP-1. Furthermore, SREBP-1 interacted with an SRE (SREBP response element) spanning at -475 to -483 bp on the ACSS2 promoter. Taken together, our results revealed a novel pathway that SREBP-1 may regulate fatty acid and TAG synthesis by regulating the expression of ACSS2. |
| Databáze: | OpenAIRE |
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