Plain language summary
Adipose tissue inflammation is the basis of obesity-related systemic inflammation, which predisposes patients to the development of metabolic and cardiovascular disease. Previous studies show that long-chain omega-3 polyunsaturated fatty acids (n-3 PUFAs) reduce cardiovascular events and exert anti-inflammatory effects but their effects on human adipose tissue inflammation have so far been unknown. This randomized open-label controlled clinical trial evaluated the effect of an 8-week treatment with n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on adipose tissue and systemic inflammation and on metabolic control. Fifty-five severely obese non-diabetic patients, scheduled for bariatric surgery, were allocated to receive either n-3 PUFAs (n=27) or an equivalent amount of butterfat as control (n=28). Systemic inflammatory markers and metabolic variables were measured at baseline and at the end of the intervention before the participants underwent bariatric surgery. Adipose tissue samples were collected during surgery for the assessment of inflammatory gene expression and lipid mediator production. Treatment with n-3 PUFAs for 8 weeks favourably affected adipose tissue and systemic inflammation. In adipose tissue, the expression of most inflammatory genes was reduced and the concentrations of lipid mediators, responsible for the resolution of inflammation (resolving lipid mediators), were increased. Systemically, the results showed a shift to a more anti-inflammatory plasma fatty acid profile and a decrease in circulating triglyceride levels. The authors concluded that the observed beneficial effects of n-3 PUFAs may be useful in the long-term treatment of obesity.
BACKGROUND Chronic adipose tissue inflammation is a hallmark of obesity, triggering the development of associated pathologies, particularly type 2 diabetes. Long-chain n-3 PUFAs reduce cardiovascular events and exert well-established antiinflammatory effects, but their effects on human adipose tissue inflammation are unknown. OBJECTIVE We investigated whether n-3 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 n-3 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 n-3 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 n-3 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 n-3 PUFA group (P = 0.04 and P = 0.03, respectively). The Pro12Ala polymorphism affected the serum cholesterol response to n-3 PUFA treatment. CONCLUSIONS Treatment with long-chain n-3 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.