Metabolic Actions of Omega-3 Fatty Acids
Condition: Metabolic Syndrome
MeSH terms: Metabolic Syndrome; Syndrome
Study type: Interventional

Summary: 
      The metabolic syndrome raises the risk of heart disease and is currently at epidemic
      proportions in the U.S. It consists of 3 of the following components: central obesity, high
      triglycerides, low HDL, abnormal blood pressure and impaired fasting glucose levels. Previous
      studies have suggested that omega-3 fish oil may influence some of these components but the
      mechanisms involved are not well understood. Therefore, this proposal will investigate how
      omega-3 fish oils affect inflammation, lipids and fat breakdown by comparing it to placebo.
      Favorable outcomes from this study could translate into a new approach to improve heart
      disease risk in men and women with the metabolic syndrome.
    

Detailed description: 
      Metabolic Actions of Omega-3 Fatty Acids on Inflammation and Adipocyte Lipolysis in the
      Metabolic Syndrome

      Epidemiological studies identify metabolic syndrome (MetS) as a biomarker of cardiovascular
      disease (CVD) risk, and recent AHA scientific statements recommend intensive lifestyle diet
      and exercise measures to reduce risk. Marine-derived omega-3 polyunsaturated fatty acids such
      as, eicosapentanoic acid (EPA) improve many constituents of the metabolic syndrome such as
      lowering fasting TG and glucose levels, inflammation, insulin resistance and blood pressure.
      These improvements may be mediated by increased fat cell storage and metabolism and lipids,
      reducing inflammation and ectopic fat deposition in visceral abdominal tissue, muscle and
      liver that results in excessive pro-inflammatory intra-abdominal fat (IAF), insulin
      resistance and reduced levels of HDL cholesterol, hallmark characteristics of the MetS. The
      anti-inflammatory actions of EPA lower acute phase reactants (APRs) and proinflammatory
      mediators are mechanisms for their lipid lowering and insulin sensitizing effects to reduce
      CVD risk. The systematic investigation of marine-derived omega-3 PUFAs on these inflammatory,
      metabolic and physiological parameters will provide new mechanistic insights for the
      therapeutic use of a potentially beneficial, safe nutraceutical, EPA in patients with MetS.
      Thus, it is our hypothesis that supplementation of marine-derived omega-3 PUFAs, will reduce
      constituents of MetS as well as systemic and tissue inflammation, insulin resistance
      (HOMA-IR), adipocyte lipolysis and cytokine release from AT to enhance TG storage capacity of
      subcutaneous AT. The reduction in inflammation and increase in insulin sensitivity will
      remodel adipose tissue to function more efficiently in TG uptake and storage; thus, reducing
      circulating FFAs and cytokines. We postulate that these metabolic effects may decrease
      ectopic fat deposition in viscera (IAF and muscle), an intriguing, novel outcome that
      provides rationale for the 9 month treatment.

      The Specific Aims are to conduct a pilot 9 month randomized trial in adults with high Tg and
      at least one other component of the MetS to compare the effects of EPA vs. placebo on:

      Aim 1: Metabolic (e.g., lipoproteins, inflammatory cytokines, acute phase reactants, glucose
      tolerance/insulin resistance) and adipose tissue responses (basal and insulin suppression of
      lipolysis (ED50), LPL activity, cytokine release and lipogenesis).

      Aim 2: Regional fat distribution quantified anthropometrically as waist and hip
      circumference, visceral and subcutaneous adipose volumes and muscle lipid accumulation by
      CT-scan and body composition (total and regional fat mass) by dual energy absorptiometry
      (DXA).

      These outcomes have potentially intriguing therapeutic implications for marine derived
      omega-3 PUFA supplementation as part of a lifestyle program for patients at increased
      cardiometabolic risk.
    

Intervention name(s): EPA (marine fatty acids); Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Subjects will be randomized to receive either EPA or placebo, four 1 gram capsules daily.; Subjects will be randomized to receive either EPA/ or placebo, four 1 gram capsules daily.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Metabolic Syndrome; Omega 3 Fish Oil