Effects of Fish Oils on Inflammation and Insulin Resistance

NCT ID: NCT00579436

Last Updated: 2018-05-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-01-31
• Study Completion Date: 2015-01-15

Brief 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.

Conditions

Metabolic Syndrome; Insulin Resistance

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

Fish oil group

4g Lovaza (omega-3 fatty acid) daily.

Group Type: ACTIVE_COMPARATOR

omega-3 fatty acid

Intervention Type: DRUG

4g of omega-3 fatty acid daily by mouth for 12 weeks.

Control group

placebo (4 non-active capsules daily)

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

4 inert capsules daily by mouth for 12 weeks.

Interventions

omega-3 fatty acid

4g of omega-3 fatty acid daily by mouth for 12 weeks.

Intervention Type: DRUG

placebo

4 inert capsules daily by mouth for 12 weeks.

Intervention Type: DRUG

Other Intervention Names

Lovaza

Eligibility Criteria

Inclusion Criteria

• BMI 27-45 kg/m2
• age 35-65 years
• abnormal carbohydrate metabolism

Exclusion Criteria

• triglycerides over 700 mg/dl
• renal disease
• liver disease
• congestive heart failure
• history of heart disease or stroke
• chronic aspirin or NSAID use (anti-coagulant)
• history of a bleeding disorder
• use of statins, fibrates, ACE inhibitors, angiotensin II receptor blockers and glucocorticoids
• diet heavy in omega-3 fatty acids (salmon, sardines, flaxseeds)

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

National Center for Research Resources (NCRR)

NIH

Sponsor Role: collaborator

Philip Kern

OTHER

Sponsor Role: lead

Responsible Party

Philip Kern

Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Philip A. Kern, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Kentucky

Locations

University of Kentucky Medical Cener

Lexington, Kentucky, United States

Countries

United States

References

Spencer M, Finlin BS, Unal R, Zhu B, Morris AJ, Shipp LR, Lee J, Walton RG, Adu A, Erfani R, Campbell M, McGehee RE Jr, Peterson CA, Kern PA. Omega-3 fatty acids reduce adipose tissue macrophages in human subjects with insulin resistance. Diabetes. 2013 May;62(5):1709-17. doi: 10.2337/db12-1042. Epub 2013 Jan 17.

Reference Type: RESULT

PMID: 23328126 (View on PubMed)

Other Identifiers

P20RR021954

Identifier Type: NIH

Identifier Source: secondary_id

View Link

74457

Identifier Type: -

Identifier Source: org_study_id