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

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 omega-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 omega-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-C-13] palmitate infusion to determine the insulin concentration needed to suppress palmitate flux by 50% (IC(50(palmitate))f). Results: In the omega-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 omega-3 group, there were no significant changes in the IC50(palmitate) f (19 +/- 2 compared with 24 +/- 6 mu IU/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 omega-3 supplementation raised plasma and adipose omega-3 fatty acid concentrations but had no beneficial effects on adipose tissue lipolysis or inflammation in insulinresistant adults.