https://scholars.lib.ntu.edu.tw/handle/123456789/605862
標題: | Docosahexaenoic acid suppresses expression of adipogenic tetranectin through sterol regulatory element-binding protein and forkhead box o protein in pigs | 作者: | Yang J.-T Chen Y.-J Huang C.-W Wang Y.-C Mersmann H.J Wang P.-H PEI-HWA WANG SHIH-TORNG DING |
關鍵字: | Adipose tissues;Docosahexaenoic acid (DHA);Forkhead box O protein (FoxO);Pigs;Sterol regulatory element-binding protein-1c (SREBP-1c);Tetranectin;cholesterol;docosahexaenoic acid;sterol regulatory element binding protein;sterol regulatory element binding protein 1c;tetranectin;transcription factor FOXO;triacylglycerol;forkhead transcription factor;lectin;adipocyte;adipogenesis;animal cell;animal experiment;animal tissue;Article;binding site;cholesterol blood level;controlled study;DNA library;embryo;gene expression;human;human cell;in vitro study;male;nonhuman;pig;promoter region;protein expression;triacylglycerol blood level;animal;drug effect;fibrinolysis;genetics;HEK293 cell line;metabolism;nutrition;Adipocytes;Adipogenesis;Animals;Docosahexaenoic Acids;Fibrinolysis;Forkhead Transcription Factors;HEK293 Cells;Humans;Lectins, C-Type;Nutritional Physiological Phenomena;Sterol Regulatory Element Binding Proteins;Swine | 公開日期: | 2021 | 卷: | 13 | 期: | 7 | 來源出版物: | Nutrients | 摘要: | Tetranectin (TN), a plasminogen-binding protein originally involved in fibrinolysis and bone formation, was later identified as a secreted adipokine from human and rat adipocytes and positively correlated with adipogenesis and lipid metabolism in adipocytes. To elucidate the nutritional regulation of adipogenic TN from diets containing different sources of fatty acids (saturated, n-6, n-3) in adipocytes, we cloned the coding region of porcine TN from a cDNA library and analyzed tissue expressions in weaned piglets fed with 2% soybean oil (SB, enriched in n-6 fatty acids), docosahexaenoic acid oil (DHA, an n-3 fatty acid) or beef tallow (BT, enriched in saturated and n-9 fatty acids) for 30 d. Compared with tissues in the BT-or SB-fed group, expression of TN was reduced in the adipose, liver and lung tissues from the DHA-fed group, accompanied with lowered plasma levels of triglycerides and cholesterols. This in vivo reduction was also confirmed in porcine primary differentiated adipocytes supplemented with DHA in vitro. Then, promoter analysis was performed. A 1956-bp putative porcine TN promoter was cloned and transcription binding sites for sterol regulatory-element binding protein (SREBP)-1c or forkhead box O proteins (FoxO) were predicted on the TN promoter. Mutating binding sites on porcine TN promoters showed that transcriptional suppression of TN by DHA on promoter activity was dependent on specific response elements for SREBP-1c or FoxO. The inhibited luciferase promoter activity by DHA on the TN promoter coincides with reduced gene expression of TN, SREBP-1c, and FoxO1 in human embryonic kidney HEK293T cells supplemented with DHA. To conclude, our current study demonstrated that the adipogenic TN was negatively regulated by nutritional modulation of DHA both in pigs in vivo and in humans/pigs in vitro. The transcriptional suppression by DHA on TN expression was partly through SREBP-1c or FoxO. Therefore, down-regulation of adipogenic tetranectin associated with fibrinolysis and adipogenesis may contribute to the beneficial effects of DHA on ameliorating obesity-induced metabolic syndromes such as atherosclerosis and adipose dysfunctions. ? 2021 by the authors. Licensee MDPI, Basel, Switzerland. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85113834604&doi=10.3390%2fnu13072315&partnerID=40&md5=24f8613ed84457b2f864992a17200acc https://scholars.lib.ntu.edu.tw/handle/123456789/605862 |
ISSN: | 20726643 | DOI: | 10.3390/nu13072315 |
顯示於: | 動物科學技術學系 |
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