Effects of Fish Oils on Inflammation and Insulin Resistance
Condition: Metabolic Syndrome; Insulin Resistance
MeSH terms: Metabolic Syndrome; Insulin Resistance; Inflammation
Study type: Interventional

Summary: 
      The purpose of this study is to determine whether improvement in fat and muscle metabolism
      after the treatment with Omacor (fish oils) provides insight into the link between obesity,
      fat and muscle function leading to metabolic syndrome, which is a risk factor for heart
      disease and diabetes.
    

Detailed description: 
      The development of type 2 diabetes (T2DM) represents a complex series of events, involving
      abnormalities in adipose tissue lipid distribution and insulin action. Along with an increase
      in adipose tissue mass is an increase in inflammation brought about by macrophages that
      infiltrate adipose tissue. These macrophages express inflammatory cytokines such as tumor
      necrosis factor (TNF) and Interleukin -6 (IL-6) which are correlated with insulin resistance
      and metabolic syndrome, and suggest that metabolic syndrome and diabetes are conditions
      characterized by a state of chronic, low-grade inflammation. Thiazolidinediones (TZDs)
      improve insulin sensitivity via activation of peroxisome proliferator-activated receptor
      (PPAR) , and there is much evidence that PPAR agonists also have anti-inflammatory
      properties.

      Fish oils are rich sources of Omega-3 fatty acids and there is a large literature on the
      potential benefits of fish oils on lowering serum triglycerides, cardiovascular protection,
      and immune modulation, and there is evidence that fish oils also activate PPAR . Hence, the
      focus of this study will be on subjects with insulin resistance and metabolic syndrome, but
      who do not yet have diabetes. We plan to treat insulin resistant subjects with fish oils and
      ask the following questions.

      Hypothesis 1. The treatment of insulin resistant subjects with fish oils will reduce adipose
      tissue inflammation.

      Aim 1. From blood samples drawn before and after treatment, we will measure levels of
      circulating inflammatory cytokines.

      Aim 2. Adipose tissue biopsies will be performed before and after fish oil treatment. From
      the adipose biopsies, we will quantitate cytokine expression, macrophage number, and we will
      look for evidence of macrophage apoptosis.

      Aim 3. We will determine whether fish oil treatment increases the adipose tissue secretion
      and serum level of the high molecular weight form of adiponectin.

      Hypothesis 2. The reduction in inflammatory markers occurs through an activation of PPAR by
      the fish oils.

      Aim 4. Adipose tissue and macrophages will be treated in vitro with fish oils in the presence
      and absence of a PPAR inhibitor. We will determine whether fish oils stimulate the secretion
      of the high molecular weight adiponectin isoform from adipose tissue and whether they induce
      apoptosis from macrophages, and whether this process is inhibited by the PPAR inhibitor.

      Hypothesis 3. Fish oils improve peripheral insulin sensitivity through a reduction in
      intramyocellular lipid, and an improvement in muscle insulin signal transduction.

      Aim 5. Before and after treatment with fish oils, insulin sensitivity will be measured, along
      with intramyocellular lipid and genes involved in insulin action and muscle lipid oxidation.
    

Intervention name(s): omega-3 fatty acid; placebo
Intervention type(s): Drug; Drug
Intervention description(s): 4g of omega-3 fatty acid daily by mouth for 12 weeks.; 4 inert capsules daily by mouth for 12 weeks.
Other intervention name(s): Lovaza
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: inflammation; obesity; diabetes