Omega-3 Supplementation Decreases Inflammation and Fetal Obesity in Pregnancy
Condition: Inflammation; Obesity; Pregnancy; Fetal Growth
MeSH terms: Obesity, Maternal; Obesity; Inflammation
Study type: Interventional

Summary: 
      Randomized, double-blind placebo controlled trial of fish oil to decrease inflammation in
      pregnancy.
    

Detailed description: 
      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.
    

Intervention name(s): Omega-3 Fish Oil
Intervention type(s): Dietary Supplement
Intervention description(s): 800mg DHA and 1200mg EPA or the equivalent of a placebo PO (by mouth) once a day from enrollment (prior to 16 weeks gestation) until delivery.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Pregnancy; Metabolic Diseases; Obesity; Fetal adiposity; Omega-3; Inflammation; Insulin Resistance