Lipid metabolism, inflammation, oxidative stress and endothelial function play important roles in the pathogenesis of cardiovascular disease (CVD), which may be affected by an imbalance in the n-6/n-3 polyunsaturated fatty acid (PUFA) ratio. This study aimed to investigate the effects of the n-6/n-3 PUFA ratio on these cardiovascular risk factors in rats fed a high-fat diet using plant oils as the main n-3 PUFA source. The 1:1 and 5:1 ratio groups had significantly decreased serum levels of total cholesterol, low-density lipoprotein cholesterol, and proinflammatory cytokines compared with the 20:1 group (p < 0.05). Additionally, the 20:1 group had significantly increased serum levels of E-Selectin, von Willebrand factor (vWF), and numerous markers of oxidative stress compared with the other groups (p < 0.05). The 1:1 group had a significantly decreased lipid peroxide level compared with the other groups (p < 0.05). Serum levels of malondialdehyde, reactive oxygen species and vWF tended to increase with n-6/n-3 PUFA ratios increasing from 5:1 to 20:1. We demonstrated that low n-6/n-3 PUFA ratio (1:1 and 5:1) had a beneficial effect on cardiovascular risk factors by enhancing favorable lipid profiles, having anti-inflammatory and anti-oxidative stress effects, and improving endothelial function. A high n-6/n-3 PUFA ratio (20:1) had adverse effects. Our results indicated that low n-6/n-3 PUFA ratios exerted beneficial cardiovascular effects, suggesting that plant oils could be used as a source of n-3 fatty acids to prevent CVD. They also suggested that we should be aware of possible adverse effects from excessive n-3 PUFA.

Background The aim of this study was to investigate the association of the formation of neutrophil extracellular traps (NETs) with gut leakage in type 1 (T1D) and type 2 diabetes (T2D). Methods In all, 105 subjects (56 T1D, 49 T2D) were included in the study. Eight biomarkers of NET formation and gut leakage (ie, protein arginine deiminase type 4 [PAD4], neutrophil elastase [NE], proteinase 3 [PR3], complement 5a [C5a], α1‐antitrypsin [AAT], DNase I, zonulin, and lipopolysaccharide [LPS]) were measured in serum samples by ELISA. Neutrophils were isolated and stimulated by phorbol myristate acetate to form NETs in vitro. Neutrophil intracellular contents were then collected and used as antigens to detect anti‐neutrophil cytoplasmic antibodies (ANCA) in the serum. Results There was an increase in NET‐associated proteins (PAD4, NE, PR3, C5a, AAT and DNase I) in new‐onset T1D patients but not in those with T2D. Of PAD4, NE, and PR3, PAD4 was found to be the most sensitive biomarker for the diagnosis of T1D. Furthermore, circulating levels of zonulin and LPS were not only increased, but were also strongly correlated with NET formation and ANCA generation in T1D patients. Conclusions This study provides evidence that increased formation of NETs, particularly PAD4, is closely associated with gut leakage in T1D but not T2D, and suggests that microorganisms and the release of neutrophil cytoplasmic antigen during the formation of NETs may be involved in the pathogenesis of T1D.