OMEGA-3 SUPPLMENTATION DECREASES INFLAMMATION AND FETAL OBESITY IN PREGNANCY

除了成年人和儿童肥胖的增加外，在过去的20年里，出生体重也有了显著的增长。根据我们的产前数据，母亲孕前肥胖是新生儿的最大风险因素，与成人肥胖一样。我们研究的目标是研究降低胎儿肥胖症的治疗策略。肥胖和怀孕都是与慢性低度感染相关的胰岛素抵抗状况。因此，我们假设孕期补充n-3多不饱和脂肪酸作为胰岛素增敏剂，可以降低外周胰岛素抵抗和炎症。如果这个机制正确的话，应该会减少母体营养对胎儿的可获得性，从而减少出生时的肥胖。我们对超重/肥胖妇女进行了一项前瞻性随机双盲对照试验，试验对象为超重/肥胖妇女，服用n-3PUFA补充剂和Ptacebo，这些妇女有过剖腹产经历，开始于早孕，并在整个怀孕期间保持。这项提议有两个具体目标。具体目的1是评估补充n-3多不饱和脂肪酸对母亲胰岛素敏感性的影响。在基础状态和饮食干预后，用Isogtt、间接测定体成分(BodPod)和血浆利培酮测定母体胰岛素敏感性和TIPI代谢。目的：评估n-3多不饱和脂肪酸对超重/肥胖孕妇胰岛素抵抗状态的影响。我们推测，n-3PUFA的支持通过阻止WAT中单核细胞的激活和巨噬细胞的聚集，从而降低全身炎性细胞因子的浓度，从而减少了妊娠期的慢性感染。我们试图表征循环单核细胞和血浆脂肪因子的纵向变化，以确定两组随着时间的推移的炎症模式。我们还利用流式细胞术、免疫组织化学和有益的基因表达测定了感染WAT的巨噬细胞的丰度和表型。此外，PPARy作为n-3PUFA作用的中心靶点的作用机制可以通过表征PPARy在WAT中的表达来检验。此外，我们还研究了n-3p-iTf4对原代培养脂肪细胞脂联素和PPARy调控基因表达的直接影响。综上所述，这项建议结合了临床和运动疗法在超重/肥胖受试者人群中的作用，以评估n-3多不饱和脂肪酸对感染和胰岛素抵抗的影响。还可以获得胎儿身体成分的初步数据，以便以后解决母体肥胖对发育中胎儿的长期不利影响(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.