Dietary ω-3 polyunsaturated fatty acids decrease retinal neovascularization by adipose-endoplasmic reticulum stress reduction to increase adiponectin
Dietary ω-3 polyunsaturated fatty acids decrease retinal neovascularization by adipose-endoplasmic reticulum stress reduction to increase adiponectin
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DOI：
10.3945/ajcn.114.099291
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发表时间：
2015-04-01
影响因子：
7.1
通讯作者：
Smith, Lois E. H.
中科院分区：
文献类型：
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作者：
Fu, Zhongjie;Lofqvist, Chatarina A.;Smith, Lois E. H.
背景：早产儿视网膜病变（ROP）是一种严重威胁早产儿视力的疾病。血清脂联素（APN）浓度与出生后生长和胎龄呈正相关，是ROP发生的重要危险因素。膳食ω-3（n-3）长链多不饱和脂肪酸目的：我们研究了APN在ROP发展中的作用以及循环APN浓度是否通过饮食omega-3 LCPUFA增加以介导ROP中的保护作用。设计：血清APN浓度与早产儿ROP的发展和血清omega-3 LCPUFA浓度相关。小鼠OIR，然后被用来确定是否ω-3 LCPUFA补充增加血清APN浓度，然后抑制retinopathy.Results：我们发现，在早产儿，低血清APN浓度呈正相关与ROP，血清APN浓度呈正相关与血清ω-3 LCPUFA浓度。在小鼠OIR中，血清总APN和生物活性高分子量APN浓度通过ω-3 LCPUFA饲料增加。白色脂肪组织是血清APN的主要来源，APN在该脂肪组织中产生并在内质网中组装。在小鼠OIR中，脂肪内质网应激增加，APN产生受到抑制。在小鼠中喂食ω-3 LCPUFA通过减少脂肪内质网应激标志物而增加APN的产生。膳食omega-3 LCPUFA对APN缺乏的新生血管形成的抑制从70%降低到10%。APN受体定位于视网膜，特别是病理性neovasculars.Conclusion：我们的研究结果表明，增加APN的omega-3 LCPUFA补充早产儿的全胃肠外营养可能会抑制ROP。
Background: Retinopathy of prematurity (ROP) is a vision-threatening disease in premature infants. Serum adiponectin (APN) concentrations positively correlate with postnatal growth and gestational age, important risk factors for ROP development. Dietary omega-3 (n-3) long-chain polyunsaturated fatty acids (omega-3 LCPUFAs) suppress ROP and oxygen-induced retinopathy (OIR) in a mouse model of human ROP, but the mechanism is not fully understood.Objective: We examined the role of APN in ROP development and whether circulating APN concentrations are increased by dietary omega-3 LCPUFAs to mediate the protective effect in ROP.Design: Serum APN concentrations were correlated with ROP development and serum omega-3 LCPUFA concentrations in preterm infants. Mouse OIR was then used to determine whether omega-3 LCPUFA supplementation increases serum APN concentrations, which then suppress retinopathy.Results: We found that in preterm infants, low serum APN concentrations positively correlate with ROP, and serum APN concentrations positively correlate with serum omega-3 LCPUFA concentrations. In mouse OIR, serum total APN and bioactive high-molecular-weight APN concentrations are increased by omega-3 LCPUFA feed. White adipose tissue, where APN is produced and assembled in the endoplasmic reticulum, is the major source of serum APN. In mouse OIR, adipose endoplasmic reticulum stress is increased, and APN production is suppressed. omega-3 LCPUFA feed in mice increases APN production by reducing adipose endoplasmic reticulum stress markers. Dietary omega-3 LCPUFA suppression of neovascularization is reduced from 70% to 10% with APN deficiency. APN receptors localize in the retina, particularly to pathologic neovessels.Conclusion: Our findings suggest that increasing APN by omega-3 LCPUFA supplementation in total parental nutrition for preterm infants may suppress ROP.