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OMEGA-3 SUPPLMENTATION DECREASES INFLAMMATION AND FETAL OBESITY IN PREGNANCY

补充 OMEGA-3 可减少妊娠期炎症和胎儿肥胖

基本信息

批准号：
7894988
负责人：
Patrick Catalano
金额：
$ 77.74万
依托单位：
CASE WESTERN RESERVE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-01 至 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7894988
关键词：
Acute-Phase Proteins Address Adipocytes Adipose tissue Adverse effects Affect Air Attenuated Birth Birth Weight Body Composition CD14 gene Chemotactic Factors Chronic Control Groups Data Deposition Diet Dietary Intervention Dietary Supplementation Double-Blind Method Environment Enzyme-Linked Immunosorbent Assay Fatty Acids Fatty acid glycerol esters Fetus Flow Cytometry Gene Expression Genes Glucose Goals Goat Growth Immunohistochemistry Indirect Calorimetry Inflammation Inflammatory Inflammatory Response Insulin Insulin Resistance Interleukin-6 Leukocytes Leukocytosis Lipids Long-Term Effects Measures Metabolic Metabolism Methodology Molecular N-3 polyunsaturated fatty acid Neonatal Nutrient Obesity Omega-3 Fatty Acids Overweight Pattern Peripheral Peripheral Blood Mononuclear Cell Phenotype Physiological Pisum sativum Placebos Placenta Plasma Play Population Pregnancy Pregnant Women Prevention Production Randomized Research Resistance Reverse Transcriptase Polymerase Chain Reaction Risk Factors Role Signal Transduction Supplementation Testing Therapeutic Time Tissues Umbilical Cord Blood Woman adipokines adiponectin basal insulin base control trial cytokine design dietary supplements fetal in utero insulin sensitivity insulin sensitizing drugs lipid metabolism macrophage monocyte neonate offspring prevent programs prospective receptor transcription factor

项目摘要

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.

过去二十年来，除了成人和儿童肥胖率的增加之外，出生体重也显着增加。根据我们的初步数据，母亲孕前肥胖是新生儿的最强危险因素，就像青少年肥胖一样。我们研究的长期山羊是为了检查减少胎儿肥胖的治疗策略。肥胖和妊娠都是与慢性低度炎症相关的胰岛素抵抗病症。因此，我们假设怀孕期间的 n-3 PUFA 膳食补充剂可充当胰岛素增敏剂，降低外周胰岛素抵抗和炎症。如果纠正这一机制，应该会减少胎儿对母体营养的利用，从而减少出生时的肥胖。我们对先前剖腹产的超重/肥胖女性进行了一项前瞻性随机双盲对照试验，其中补充 n-3 PUFA 和 ptacebo，在早孕期开始并在整个怀孕期间维持。该提案有两个具体目标。具体目标 1 是评估补充 n-3 PUFA 对孕妇胰岛素敏感性的影响。使用lsogtt、间接量热法身体成分(BODPOD)和基线时以及饮食干预后的血浆胰岛素敏感性和代谢率来测量母体胰岛素敏感性和代谢率。具体目标 2 评估 n-3 PUFA 对超重/肥胖孕妇炎症状态的影响。我们假设补充 n-3 PUFA 可通过防止单核细胞活化和 WAT 中巨噬细胞的积累来减少妊娠期间的慢性炎症，从而降低促炎细胞因子的全身浓度。我们打算描述循环单核细胞和血浆脂肪因子的纵向变化，以便定义两组随时间推移的炎症模式。我们还使用流式细胞术、免疫组织化学和基因表达分析来确定浸润 WAT 的巨噬细胞的丰度和表型。此外，通过表征补充组和对照组 WAT 中 PPARγ 的表达，可以检查 PPARγ 作为 n-3 PUFA 调节胰岛素敏感性作用的中心靶标的作用。此外，我们还研究了 n-3 pÙf4 对原代切割脂肪细胞中脂联素和 PPARy 调节基因表达的直接影响。总之，该提案结合了超重/肥胖受试者群体的临床方法和预测方法，以评估 n-3 PUFA 对炎症和胰岛素抵抗的影响。还可以获得有关胎儿身体成分的初步数据，以便随后解决母亲肥胖对发育中胎儿的长期不利影响（发育规划）的预防问题。