Very-long-chain -3 fatty acid supplements and adipose tissue functions: a randomized controlled trial.

Increased omega-3 (n-3) fatty acid consumption is reported to benefit patients with metabolic syndrome, possibly due to improved adipose tissue function. We tested the effects of high-dose, very-long-chain ω-3 fatty acids on adipose tissue inflammation and insulin regulation of lipolysis. 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 ω-3/d; = 12) with a placebo (4.2 g oleate/d; = 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-C]palmitate infusion to determine the insulin concentration needed to suppress palmitate flux by 50% (ICf). In the ω-3 group, the EPA and DHA contributions to plasma free fatty acids increased ( = 0.0003 and = 0.003, respectively), as did the EPA and DHA content in adipose tissue ( < 0.0001 and < 0.0001, respectively). Despite increases in adipose and plasma EPA and DHA in the ω-3 group, there were no significant changes in the ICf (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. Six months of high-dose ω-3 supplementation raised plasma and adipose ω-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.