Polyunsaturated fatty acids regulate inflammatory responses through the production of eicosanoids including prostaglandins (PGs), thromboxanes (TXs) and leukotrienes (LTs) . To our knowledge, this is the first study evaluating early postoperative effects of LSG on plasma PUFA levels. Plasma AA (C20:4n6) levels and AA/EPA ratio were significantly increased in sleeve gastrectomy patients after postoperation oral feeding compared to postoperation day 1. The observed significant increase of plasma AA levels following LSG may be due to increased peripheral insulin sensitivity. In agreement with previous studies [7, 16] we have observed a significant reduction in insulin levels occurring very early at 4–5 days following sleeve gastrectomy with a significant reduction in insulin resistance. It was recently shown that insulin initiation therapy significantly increased plasma levels of AA (C20:4n6) compared to before treatment levels in T2DM patients . Disturbed fatty acid metabolism is an important feature of the insulin-resistant state . Essential fatty acids are metabolized into more physiologically active compounds by introduction of further double bonds by delta-5- and delta-6-desaturase enzymes . Emerging evidence shows that delta-5 desaturase is the key regulator in the synthesis of PUFA and is modulated by factors including adiposity, diet and insulin resistance . The hepatic microsomal delta-6-desaturation of LA and ALA was found to be depressed in alloxan induced diabetic rats . The observed enzymatic defect was corrected by insulin injection in 2 days .
High levels of saturated fatty acids and low amounts of PUFAs are associated with obesity . Omega-3 PUFA enriched diet increases expression of genes involved in glucose transport [glucose transporter type 4 (GLUT-4)] and insulin signaling [insulin receptor substrate 1 (IRS-1)], as well as genes involved in insulin sensitivity [peroxisome proliferator-activated receptor gamma (PPARγ)] . In an insulin-resistant state, omega-3 PUFAs bind to the G-protein coupled receptor 120 (GPR120), resulting in reduced cytokine production from inflammatory macrophages and improved signaling in adipocytes, leading to a reduction in insulin resistance . In this study, we have observed a significant increase in AA/EPA ratio in sleeve gastrectomy patients after postoperation oral feeding compared to preoperation levels. This finding suggests that improved insulin sensitivity in obese patients immediately after sleeve gastrectomy in not related to changes in omega-3 PUFA levels.
Low serum EPA/AA ratio was recently reported in male subjects with visceral obesity . Likewise, an imbalance of dietary long-chain PUFAs, especially high omega-6/omega-3 PUFA ratio, was associated with increased risk of cardiovascular disease . We have observed that AA (C20:4n6)/DHA(C22:6n3) ratio was significantly higher in sleeve gastrectomy patients at preoperation, postoperation day 1 and after postoperation oral feeding when compared to control group subjects. The significant increase of PGE2 levels and AA/DHA ratio in all performed measurements in the sleeve gastrectomy group patients supports the presence of a proinflammatory state in obesity. Competition between omega-6 and omega-3 fatty acids occurs in the production of eicosanoids by stereospecific lipid-oxidizing enzymes cylooxygenase (COX) and lipoxygenase (LOX) . Docosahexaenoic acid (DHA, C22:6n3) is a precursor of eicosanoids with less marked inflammatory effect. On the other hand, AA is a precursor of eicosanoids with definite inflammatory effect . Hence, increased AA to DHA ratio indicates more precursor for the synthesis of highly inflammatory eicosanoids.
As stated in the introduction of the manuscript, restoration of the first phase of insulin secretion and improved insulin sensitivity in diabetic obese patients immediately after sleeve gastrectomy, before any weight loss, seem to be related to hormonal changes of possible gastric origin and is neither meal- nor weight-change-related . Significantly increased AA levels in sleeve gastrectomy patients after postoperation oral feeding may play a constructive role in the observed improved insulin sensitivity in sleeve gastrectomy patients. It was previously observed that patients with type 2 diabetes mellitus have low AA content in their plasma phospholipid fraction and it was suggested that AA deficiency may predispose humans to develop T2DM . In support of these findings it was recently demonstrated that insulin analog initiation therapy in T2DM patients increased AA in human plasma (11). The role of AA as a possible endogenous anti-diabetic molecule is discussed comprehensively in a recent review .
Limitation of our study include: 1) the study covers a small cohort; 2) the study has a nonrandomized design because patients were assigned to either group according to clinical criteria; 3) The study population included an unequal percentage of male patients. However, the limitation of gender distribution has been minimized by matching the control group similarly.
In summary, we have observed a significant decrease in insulin and HOMA IR levels in sleeve gastrectomy patients after postoperation oral feeding compared to preoperation. This was accompanied by significantly increased plasma AA levels. The significant increase in PGE2 levels and AA/DHA ratio in sleeve gastrectomy group patients also confirms the presence of a proinflammatory state in obesity.