Very-long-chain {omega}-3 fatty acid supplements and adipose tissue functions: a randomized controlled trial [Dietary supplements]

Background: Increased omega-3 (n–3) fatty acid consumption is reported to benefit patients with metabolic syndrome, possibly due to improved adipose tissue function.

Objective: We tested the effects of high-dose, very-long-chain -3 fatty acids on adipose tissue inflammation and insulin regulation of lipolysis.

Design: A double-blind, placebo-controlled study compared 6 mo of 3.9 g eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)/d (4.2 g total -3/d; n = 12) with a placebo (4.2 g oleate/d; n = 9) in insulin-resistant adults. Before and after treatment, the volunteers underwent adipose tissue biopsies to measure the total (CD68⁺), pro- (CD14⁺ = M1), and anti- (CD206⁺ = M2) inflammatory macrophages, crown-like structures, and senescent cells, as well as a 2-step pancreatic clamping with a [U-¹³C]palmitate infusion to determine the insulin concentration needed to suppress palmitate flux by 50% (IC_{50(palmitate)}f).

Results: In the -3 group, the EPA and DHA contributions to plasma free fatty acids increased (P = 0.0003 and P = 0.003, respectively), as did the EPA and DHA content in adipose tissue (P < 0.0001 and P < 0.0001, respectively). Despite increases in adipose and plasma EPA and DHA in the -3 group, there were no significant changes in the IC_{50(palmitate)}f (19 ± 2 compared with 24 ± 3 μIU/mL), adipose macrophages (total: 31 ± 2/100 adipocytes compared with 33 ± 2/100 adipocytes; CD14⁺: 13 ± 2/100 adipocytes compared with 14 ± 2/100 adipocytes; CD206⁺: 28 ± 2/100 adipocytes compared with 29 ± 3/100 adipocytes), crown-like structures (1 ± 0/10 images compared with 1 ± 0/10 images), or senescent cells (4% ± 1% compared with 4% ± 1%). There were no changes in these outcomes in the placebo group.

Conclusions: Six months of high-dose -3 supplementation raised plasma and adipose -3 fatty acid concentrations but had no beneficial effects on adipose tissue lipolysis or inflammation in insulin-resistant adults. This trial was registered at clinicaltrials.gov as NCT01686568.

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