Conditions: Insulin Resistance
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 31
Healthy volunteers: yes

Brief summary:
This study is being done to understand the effects of dietary omega-3 fats on insulin sensitivity in adult men and women.

Detailed description:
Dietary omega-3 polyunsaturated fatty acids (n-3 PUFA), which include eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from fish oil, prevent insulin resistance in rodents, but data in humans is ambiguous. No existing studies have systematically evaluated the influence of n-3 PUFAs on insulin sensitivity and beta cell function in insulin resistant, non-diabetic humans. The Investigators hypothesize that 6 months of oral supplementation of purified EPA/DHA (3.9g/day) will significantly improve hepatic and peripheral insulin sensitivity and beta cell responsiveness in insulin-resistant, non-diabetic individuals. Based on recent work in mice, the investigators also hypothesize that EPA/DHA will increase the content and function of mitochondria in skeletal muscle, measured using a combination of in vivo and in vitro methods. Overall, the investigators hypothesize that EPA+DHA supplementation will improve hepatic and peripheral insulin sensitivity in insulin resistant humans, and this improvement will be associated with mitochondrial biogenesis and attenuated lipid accumulation in skeletal muscle and liver.

A sub-study was added in which participants receiving dietary omega-3 fatty acids or placebo supplements underwent abdominal subcutaneous adipose tissue biopsies to measure the content of total, pro- (M1) and anti- (M2) inflammatory macrophages (immunohistochemistry), crown-like structures (immunohistochemistry), and senescent cells (β-galactosidase staining), as well as a two-step euglycemic, pancreatic clamp with a stable-isotope labeled precursor ((U-13C)palmitate) infusion to determine the insulin concentration needed to suppress palmitate flux by 50% (IC50(palmitate)f).

Arms:
arm 1: Patients in this group will receive oral supplementation with EPA+DHA (3.9grams/day) for 6 months. arm 2: Patients in this group will be supplemented with placebo capsules containing ethyl oleate.

Interventions: intervention 1: Omega-3 intervention 2: placebo
Intervention descriptions: intervention 1: Patients in this group will receive oral supplementation with EPA+DHA (3.9grams/day) for 6 months. intervention 2: None

Protocol document: