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 p?f4 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 inftamm?tion 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.
| Berggren, E K; O'Tierney-Ginn, P; Lewis, S et al. (2017) Variations in resting energy expenditure: impact on gestational weight gain. Am J Obstet Gynecol 217:445.e1-445.e6 |
| Berggren, Erica K; Groh-Wargo, Sharon; Presley, Larraine et al. (2016) Maternal fat, but not lean, mass is increased among overweight/obese women with excess gestational weight gain. Am J Obstet Gynecol 214:745.e1-5 |
| Calabuig-Navarro, Virtu; Puchowicz, Michelle; Glazebrook, Patricia et al. (2016) Effect of ?-3 supplementation on placental lipid metabolism in overweight and obese women. Am J Clin Nutr 103:1064-72 |
| Basu, Subhabrata; Haghiac, Maricela; Surace, Peter et al. (2011) Pregravid obesity associates with increased maternal endotoxemia and metabolic inflammation. Obesity (Silver Spring) 19:476-82 |
| de Castro, J; Sevillano, J; Marciniak, J et al. (2011) Implication of low level inflammation in the insulin resistance of adipose tissue at late pregnancy. Endocrinology 152:4094-105 |
