Influence of resveratrol and resveratol enriched extracts on endogenous synthesis longchained omega-3-fatty acids - Studies in cell culture in vitro and in rainbow trout and seabass in aquaculture

白藜芦醇和白藜芦醇富集提取物对内源合成长链 omega-3 脂肪酸的影响 - 体外细胞培养以及水产养殖中虹鳟鱼和鲈鱼的研究

• 批准号: 251894753
• 负责人: Professor Dr. Gerald Rimbach
• 金额: --
• 依托单位: Institut für Tierzucht und Tierhaltung
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2016-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/251894753?language=en
• 关键词: Influence; resveratrol; resveratol; enriched; extracts

Eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) belong to the long-chain polyunsaturated fatty acid family (LCPUFA) and exhibit significant health benefits in humans. Both fatty acids are centrally involved in the regulation of triglyceride levels, inflammatory processes and neuronal development. Fish is the major source for LCPUFA in human diets. Fish grown in aquaculture has to be supplemented with dietary LCPUFA to maintain fish health and product quality as conversion rates of dietary alpha-linolenic acid to EPA and DHA are poor both in freshwater fish species and especially in seawater fish species. Thus innovative strategies are needed to improve endogenous LCPUFA synthesis in aquaculture fish species. Delta6-desaturation seems to be the rate-limiting step in LCPUFA-synthesis. Delta6-desaturase converts alpha-linolenic acid into stearidonic acid which is further processed to EPA and DHA. We have identified the stilbene resveratrol as a potent inducer of delta6-desaturation in cultured hepatocytes. Resveratrol enhanced delta6-desaturase mRNA and protein levels as well EPA/DHA concentrations in hepatocytes in vitro. Within this grant proposal we aim to investigate the impact of resveratrol on LCPUFA metabolism in vivo. To this end rainbow trouts (fresh water) and sea bass (seawater) will be supplemented with resveratrol at varying water temperatures. We will measure delta6-desaturase, EPA/DHA levels and fatty acid composition in plasma, liver and filet in fish. Furthermore underlying molecular mechanisms by which resveratrol affects EPA and DHA synthesis will be examined in vitro in D11-trout hepatocytes. D11-cells will be treated with non-cytotoxic concentrations of resveratrol for the determination of fatty acid spectra and delta6-desaturase activities. Furthermore RNAi and electro mobility shift assays will be used to identify putative transcription factors (PPARalpha, STAT, HNF1, RXR, ER) involved in the resveratrol mediated induction of delta6-desaturase.

二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）属于长链多不饱和脂肪酸家族（LCPUFA），对人体健康有显著的益处。这两种脂肪酸主要参与甘油三酯水平、炎症过程和神经元发育的调节。鱼类是人类饮食中LCPUFA的主要来源。水产养殖中生长的鱼类必须补充膳食中的LCPUFA，以保持鱼类健康和产品质量，因为淡水鱼类尤其是海水鱼类的膳食中α-亚麻酸转化为EPA和DHA的转化率很低。因此，需要创新的策略来提高水产养殖鱼类内源性LCPUFA的合成。δ 6去饱和似乎是LCPUFA合成中的限速步骤。Δ 6-去饱和酶将α-亚麻酸转化为十八碳四烯酸，十八碳四烯酸进一步加工为EPA和DHA。我们已经确定了芪白藜芦醇作为一个有效的诱导剂delta 6-去饱和培养的肝细胞。白藜芦醇增强delta 6-去饱和酶mRNA和蛋白水平以及EPA/DHA浓度在体外肝细胞。在这项资助计划中，我们的目标是研究白藜芦醇对体内LCPUFA代谢的影响。为此，虹鳟鱼（淡水）和海鲈鱼（海水）将在不同的水温下补充白藜芦醇。我们将测量鱼类血浆、肝脏和鱼片中的δ 6-去饱和酶、EPA/DHA水平和脂肪酸组成。此外，白藜芦醇影响EPA和DHA合成的潜在分子机制将在体外D11鳟鱼肝细胞中进行研究。D11-细胞将用非细胞毒性浓度的白藜芦醇处理，以测定脂肪酸谱和δ 6-去饱和酶活性。此外，RNAi和电迁移率变动分析将用于鉴定参与白藜芦醇介导的δ 6-去饱和酶诱导的推定转录因子（PPARalpha、STAT、HNF 1、RXR、ER）。