Fu Zhongjie, Lofqvist Chatarina A, Shao Zhuo, Sun Ye, Joyal Jean-Sebastien, Hurst Christian G, Cui Ricky Z, Evans Lucy P, Tian Katherine, SanGiovanni John Paul, Chen Jing, Ley David, Hansen Pupp Ingrid, Hellstrom Ann, Smith Lois E H
From the Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA (ZF, ZS, YS, J-SJ, CGH, RZC, LPE, KT, JC, and LEHS); the Department of Ophthalmology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (CAL and AH); the Department of Pediatrics, Institute of Clinical Sciences Lund, Lund University and Skåne University Hospital, Lund, Sweden (DL and IHP); and National Eye Institute, Division of Epidemiology and Clinical Research Clinical Trials Branch, National Eye Institute, NIH, Bethesda, MD (JPS).
Am J Clin Nutr. 2015 Apr;101(4):879-88. doi: 10.3945/ajcn.114.099291. Epub 2015 Feb 4.
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 ω-3 (n-3) long-chain polyunsaturated fatty acids (ω-3 LCPUFAs) suppress ROP and oxygen-induced retinopathy (OIR) in a mouse model of human ROP, but the mechanism is not fully understood.
We examined the role of APN in ROP development and whether circulating APN concentrations are increased by dietary ω-3 LCPUFAs to mediate the protective effect in ROP.
Serum APN concentrations were correlated with ROP development and serum ω-3 LCPUFA concentrations in preterm infants. Mouse OIR was then used to determine whether ω-3 LCPUFA supplementation increases serum APN concentrations, which then suppress retinopathy.
We found that in preterm infants, low serum APN concentrations positively correlate with ROP, and serum APN concentrations positively correlate with serum ω-3 LCPUFA concentrations. In mouse OIR, serum total APN and bioactive high-molecular-weight APN concentrations are increased by ω-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. ω-3 LCPUFA feed in mice increases APN production by reducing adipose endoplasmic reticulum stress markers. Dietary ω-3 LCPUFA suppression of neovascularization is reduced from 70% to 10% with APN deficiency. APN receptors localize in the retina, particularly to pathologic neovessels.
Our findings suggest that increasing APN by ω-3 LCPUFA supplementation in total parental nutrition for preterm infants may suppress ROP.
早产儿视网膜病变（ROP）是一种威胁早产儿视力的疾病。血清脂联素（APN）浓度与出生后生长及胎龄呈正相关，而胎龄是ROP发生的重要危险因素。在人类ROP小鼠模型中，膳食ω-3（n-3）长链多不饱和脂肪酸（ω-3 LCPUFAs）可抑制ROP和氧诱导性视网膜病变（OIR），但其机制尚未完全明确。
我们研究了APN在ROP发生中的作用，以及膳食ω-3 LCPUFAs是否通过提高循环APN浓度来介导对ROP的保护作用。
检测早产儿血清APN浓度与ROP发生及血清ω-3 LCPUFA浓度的相关性。然后利用小鼠OIR模型确定补充ω-3 LCPUFAs是否能提高血清APN浓度，进而抑制视网膜病变。
我们发现，在早产儿中，低血清APN浓度与ROP呈正相关，且血清APN浓度与血清ω-3 LCPUFA浓度呈正相关。在小鼠OIR模型中，ω-3 LCPUFA喂养可提高血清总APN和生物活性高分子量APN浓度。APN在内质网中产生和组装的白色脂肪组织是血清APN的主要来源。在小鼠OIR模型中，脂肪组织内质网应激增加，APN产生受到抑制。小鼠食用ω-3 LCPUFA饲料可通过降低脂肪组织内质网应激标志物来增加APN的产生。APN缺乏时，膳食ω-3 LCPUFA对新生血管形成的抑制作用从70%降至10%。APN受体定位于视网膜，尤其是病理性新生血管。
我们的研究结果表明，在早产儿全肠外营养中补充ω-3 LCPUFAs以提高APN水平可能会抑制ROP。
