OMEGA-3 SUPPLMENTATION DECREASES INFLAMMATION AND FETAL OBESITY IN PREGNANCY

在过去的20年里，除了成年人和儿童肥胖症的增加外，出生体重也有显著的增加。根据我们的前期数据，母亲孕前肥胖是新生儿最强的危险因素，因为我们[[作为adotescent肥胖。我们的研究目的是检验减少胎儿肥胖的治疗策略.肥胖和妊娠都是与慢性低度感染相关的胰岛素抵抗状态。因此，我们假设在怀孕期间，n-3 PUFA膳食补充剂将作为胰岛素增敏剂，降低外周胰岛素抵抗和炎症。如果纠正这种机制，将减少母体营养素对胎儿的利用率，从而减少出生时的肥胖。我们在超重/肥胖妇女中进行了一项前瞻性随机双盲对照试验，在妊娠早期开始补充n-3 PUFA和ptacebo，并在整个妊娠期间维持。这项建议有两个具体目标。具体目标1是评价补充n-3 PUFA对母亲胰岛素敏感性的影响。在实验开始时和干预后分别用Lsogtt、间接比色法测定体成分（BODPOD）和血浆脂质过氧化物（TP），测定母体胰岛素敏感性和TPI代谢。第二个具体目的是评估n-3 PUFA对超重/肥胖孕妇的妊娠状态的影响。我们推测，n-3 PUFA通过阻止单核细胞活化和巨噬细胞在WAT中的积累，从而降低促炎细胞因子的全身浓度，从而减少妊娠期间的慢性炎症。我们试图描述循环单核细胞和血浆脂肪因子的纵向变化，以确定两组随时间的炎症模式。我们还将通过流式细胞术、免疫组织化学和基因表达检测来确定巨噬细胞浸润WAT的丰度和表型。此外，PPARy作为n-3 PUFA调节胰岛素敏感性作用的中心靶点的作用将通过表征支持组和对照组WAT中PPARy的表达来检查。此外，我们还将研究n-3 pGF 4对原代培养的脂肪细胞脂联素和PPARy调控基因表达的直接影响。总之，该建议在超重/肥胖受试者群体中结合临床和皮肤方法，以评估n-3 PUFA对胰岛素抵抗和胰岛素抵抗的影响。还将获得关于胎儿身体组成的初步数据，以便以后解决母体肥胖对发育中胎儿的长期不良影响（发育规划）的预防。

ln addition to the increase in obesity in adutt and chitdren, there has been a significant increase in birth weights over the tast 2 decades. Based on our pretiminary data, maternal pregravid obesity is the strongest risk factor for neonatal as we[[ as adotescent obesity. The [ong' ierm goats of our research are to examine therapeutic strategies to decrease fetal adiposity. Obesity and pregnancy are both insutin resistant conditions associated with chronic low-grade inftammation. Therefore, we hypothesize that n-3 PUFA dietary supplements during pregnancy witl act as insulin sensitizers decreasing peripheral insulin resistance and inflammation. lf correct this mechanism should decrease avaitabitity of maternal nutrients to the fetus and subsequently reduce adiposity at birth. We ptan a prospective randomized double btind control triat of n-3 PUFA supplementation and ptacebo in overweight/obese women, with a previous cesarean delivery, initiated in earty pregnancy and maintained throughout pregnancy. This proposal has two specific aims. Specific aim 1 is to evatuate the effect of n-3 PUFA supplementation on maternat insulin sensitivitv. Measures of maternat insutin sensitivity and tipi{ metabolism witl be made using the lsogtt, indirect catorimetry body composition (BODPOD) and plasma tipid profite at basetine and after dietary intervention. jpecific aim 2 witt assess the effect of n-3 PUFA on the inftammatorv status in overweieht/obese preqnant women. We hypothesize that n-3 PUFA supptementation decreases cl'rronic inftammation during pregnancy by preventing monocyte activation and accumulation of macrophages in WAT thus lowering systemic concentration of proinflammatory cytokines. We ptan to characterize the longitudinal changes in circutating monocytes and plasma adipokines in order to define the inflammatory patterns in both groups over time. We witt also determine the abundance and phenotype of macrophages infittrating WAT using flow cytometry, immunohistochemistry and gene expression profiting. Furthermore, the rote of PPARy as a central target of n-3 PUFA action to regutate insutin sensitivity witt be examined by characterizing the expression of PPARy in WAT of both supptemented and control groups. Additionatty, w€ witl investigate the direct affect of n-3 pÙf4 on the expression of adiponectin and PPARy regulated genes in primary cuttured adipocytes. ln'summary, this proposal combines both ctinical and motecutar methodotogies in an overweight/obese subject population in order to assess the effect of n-3 PUFA on inftammãtion and insuiin resistance. Pretiminary data witt also be obtained on fetat body composition in order to later address the prevention of the long term adverse effects (devetopmental programming) of maternal obesity in the developing fetus.