Long-chain n23 PUFAs reduce adipose tissue and systemic inflammation in severely obese nondiabetic patients: a randomized

Background: Chronic adipose tissue inflammation is a hallmark of obesity, triggering the development of associated pathologies, particularly type 2 diabetes. Long-chain n23 PUFAs reduce cardiovascular events and exert well-established antiinflammatory effects, but their effects on human adipose tissue inflammation are unknown. Objective: We investigated whether n23 PUFAs reduce adipose tissue inflammation in severely obese nondiabetic patients. Design: We treated 55 severely obese nondiabetic patients, scheduled to undergo elective bariatric surgery, with 3.36 g long-chain n23 PUFAs/d (EPA, DHA) or an equivalent amount of butterfat as control, for 8 wk, in a randomized open-label controlled clinical trial. The primary efficacy measure was inflammatory gene expression in visceral and subcutaneous adipose tissue samples (subcutaneous adipose tissue and visceral adipose tissue), collected during surgery after the intervention. Secondary efficacy variables were adipose tissue production of antiinflammatory n23 PUFA‐derived eicosanoids, plasma concentrations of inflammatory markers, metabolic control, and the effect of the Pro12Ala PPARG polymorphism on the treatment response. Results: Treatment with n23 PUFAs, which was well tolerated, decreased the gene expression of most analyzed inflammatory genes in subcutaneous adipose tissue (P , 0.05) and increased production of antiinflammatory eicosanoids in visceral adipose tissue and subcutaneous adipose tissue (P , 0.05). In comparison with control subjects who received butterfat, circulating interleukin-6 and triglyceride concentrations decreased significantly in the n23 PUFA group (P = 0.04 and P = 0.03, respectively). The Pro12Ala polymorphism affected the serum cholesterol response to n23 PUFA treatment. Conclusions: Treatment with long-chain n23 PUFAs favorably modulated adipose tissue and systemic inflammation in severely obese nondiabetic patients and improved lipid metabolism. These effects may be beneficial in the long-term treatment of obesity. This trial was registered at clinicaltrials.gov as NCT00760760. Am J Clin Nutr doi: 10.3945/ajcn.112.037432.