Obesity Clinical Trial
Official title:
Omega-3 Supplementation Decreases Inflammation and Fetal Obesity in Pregnancy
Randomized, double-blind placebo controlled trial of fish oil to decrease inflammation in pregnancy.
In addition to the increase in obesity in adult and children, there has been a significant
increase in birth weights over the last 2 decades. Based on our preliminary data, maternal
pre-gravid obesity is the strongest risk factor for neonatal as well as adolescent obesity.
The long-term goals of our research are to examine therapeutic strategies to decrease fetal
adiposity. Obesity and pregnancy are both insulin resistant conditions associated with
chronic low-grade inflammation. Therefore, we hypothesize that n-3 PUFA dietary supplements
during pregnancy will act as insulin sensitizers decreasing peripheral insulin resistance and
inflammation. If correct this mechanism should decrease availability of maternal nutrients to
the fetus and subsequently reduce adiposity at birth. We plan a prospective randomized double
blind control trial of n-3 PUFA supplementation and placebo in overweight/obese women, with a
previous cesarean delivery, initiated in early pregnancy and maintained throughout pregnancy.
This proposal has two specific aims. Specific aim 1 is to evaluate the effect of n-3 PUFA
supplementation on maternal insulin sensitivity. Measures of maternal insulin sensitivity and
lipid metabolism will be made using the ISogtt, indirect calorimetry body composition
(BODPOD) and plasma lipid profile at baseline and after dietary intervention.
Specific aim 2 will assess the effect of n-3 PUFA on the inflammatory status in
overweight/obese pregnant women. We hypothesize that n-3 PUFA supplementation decreases
chronic inflammation during pregnancy by preventing monocyte activation and accumulation of
macrophages in WAT thus lowering systemic concentration of pro-inflammatory cytokines. We
plan to characterize the longitudinal changes in circulating monocytes and plasma adipokines
in order to define the inflammatory patterns in both groups over time. We will also determine
the abundance and phenotype of macrophages infiltrating WAT using flow cytometry,
immunohistochemistry and gene expression profiling. Furthermore, the role of PPARγ as a
central target of n-3 PUFA action to regulate insulin sensitivity will be examined by
characterizing the expression of PPARγ in WAT of both supplemented and control groups.
Additionally, we will investigate the direct affect of n-3 PUFA on the expression of
adiponectin and PPARγ regulated genes in primary cultured adipocytes.
In summary, this proposal combines both clinical and molecular methodologies in an
overweight/obese subject population in order to assess the effect of n-3 PUFA on inflammation
and insulin resistance. Preliminary data will also be obtained on fetal body composition in
order to later address the prevention of the long term adverse effects (developmental
programming) of maternal obesity in the developing fetus.
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