关键词: SREBP1 Sparus aurata chitosan gene delivery growth liver

Mesh : Animals Sea Bream / metabolism Glucose / metabolism Chitosan / chemistry Sterol Regulatory Element Binding Protein 1 / genetics metabolism Liver / metabolism Perciformes / metabolism Dietary Carbohydrates Diet Sterols / metabolism Lipids

来  源:   DOI:10.3390/md21110562   PDF(Pubmed)

Abstract:
The administration of a single dose of chitosan nanoparticles driving the expression of sterol regulatory element-binding protein 1a (SREBP1a) was recently associated with the enhanced conversion of carbohydrates into lipids. To address the effects of the long-lasting expression of SREBP1a on the growth and liver intermediary metabolism of carnivorous fish, chitosan-tripolyphosphate (TPP) nanoparticles complexed with a plasmid expressing the N terminal active domain of hamster SREBP1a (pSG5-SREBP1a) were injected intraperitoneally every 4 weeks (three doses in total) to gilthead sea bream (Sparus aurata) fed high-protein-low-carbohydrate and low-protein-high-carbohydrate diets. Following 70 days of treatment, chitosan-TPP-pSG5-SREBP1a nanoparticles led to the sustained upregulation of SREBP1a in the liver of S. aurata. Independently of the diet, SREBP1a overexpression significantly increased their weight gain, specific growth rate, and protein efficiency ratio but decreased their feed conversion ratio. In agreement with an improved conversion of dietary carbohydrates into lipids, SREBP1a expression increased serum triglycerides and cholesterol as well as hepatic glucose oxidation via glycolysis and the pentose phosphate pathway, while not affecting gluconeogenesis and transamination. Our findings support that the periodical administration of chitosan-TPP-DNA nanoparticles to overexpress SREBP1a in the liver enhanced the growth performance of S. aurata through a mechanism that enabled protein sparing by enhancing dietary carbohydrate metabolisation.
摘要:
最近,施用单剂量的壳聚糖纳米颗粒驱动固醇调节元件结合蛋白1a(SREBP1a)的表达与碳水化合物向脂质的转化增强有关。为了解决SREBP1a的持久表达对食肉鱼类生长和肝脏中介代谢的影响,将与表达仓鼠SREBP1a(pSG5-SREBP1a)的N末端活性域的质粒复合的壳聚糖-三聚磷酸盐(TPP)纳米颗粒每4周(总共三个剂量)腹膜内注射一次给喂食高蛋白-低碳水化合物和低蛋白-高碳水化合物饮食的金鱼(Sparusaurata)。经过70天的治疗,壳聚糖-TPP-pSG5-SREBP1a纳米颗粒导致SREBP1a在S.aurata肝脏中持续上调。独立于饮食,SREBP1a过表达显著增加其体重增加,比增长率,和蛋白质效率比,但降低了它们的饲料转化率。与改善膳食碳水化合物向脂质的转化一致,SREBP1a表达通过糖酵解和磷酸戊糖途径增加血清甘油三酯和胆固醇以及肝脏葡萄糖氧化,而不影响糖异生和转氨作用。我们的研究结果支持,定期施用壳聚糖-TPP-DNA纳米颗粒以在肝脏中过表达SREBP1a,通过一种通过增强饮食碳水化合物代谢来节省蛋白质的机制来增强S.aurata的生长性能。
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