Prostaglandins, leukotrienes, and essential fatty acids最新文献

Due to their multiple mechanisms of biological action, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been the focus of ongoing active research for decades. In spite of the resulting body of knowledge, there remain significant gaps in our understanding of EPA/DHA health effects. Further, the volume of existing research makes it challenging to conduct systematic investigations to identify or resolve those gaps.

The purpose of this article is to introduce the GOED Clinical Study Database (CSD), a comprehensive, manually-curated relational database that catalogs this research.

To study the pathophysiological roles of the fatty acid-binding proteins (FABPs) within the retina, we performed; (1) immunolabeling of human retinas, wild type (WT) rat and mouse retinas, rat models for diabetic retinopathy (DR) and retinitis pigmentosa (RP) with anti-FABP3, FABP4, FABP5, FABP7, FABP8 and FABP12, (2) electroretinogram (ERG) measurements of WT and FABP4-deficient (Fabp4^-/-) mice, (3) ELISA or gas chromatography measurements of plasma (P-) and vitreous (V-) levels of FABP4 and vascular endothelial growth factor A (VEGFA), and fatty acids (FAs) from patients with retinal vascular disease (RVD) including proliferative DR (PDR, n = 30) and retinal vein occlusion (RVO, n = 18) and non-RVD (n = 18). Within the human retina, diverse expressions of FABP3, FABP4, FABP7 and FABP8 were identified. In contrast, positive immunoreactivities toward only FABP4 and FABP12 were detected in the cases of rat and mouse retinas, and interestingly, the FABP4 labeling patterns for the WT, DR and RP rat retinas were different. The ERG amplitudes of Fabp4^-/- mice were enhanced compared with those of WT mice. The concentrations of V-FABP4, V-VEGFA and total FAs were significantly higher in RVD patients than in non-PDR patients (P < 0.05). The V-FAs levels of each were significantly and positively correlated with V-FABP4 and V-VEGFA, although no significant correlation between vitreous (V-) and plasma (P-) FABP4, VEGFA and FAs were detected. The current study reveals that V-FAs appear to have significant roles in both retinal physiology as well as the pathogenesis of RVD with FABP4, which is commonly expressed within the retina in most species.

Background

: The effect of omega-3 polyunsaturated fatty acids (n-3 PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on cardiovascular risk modification in type 2 diabetes and related complications remain unclear. We aim to assess the published effects of n-3 PUFA interventions on lipid risk factors in type 2 diabetes.

Methods

: We searched the literature on Pubmed, Embase, CENTRAL, and Web of Science databases in order to perform a pooled analysis of randomized clinical trials (RCTs) assessing n-3 PUFA interventions in type 2 diabetes. The primary outcomes analyzed were the effect of n -3 PUFAs on metabolic biomarkers in type 2 diabetes.

Results

: 46 RCTs involving 4991 patients with type 2 diabetes were identified for further analysis. Analysis of results showed that n-3 PUFAs interventions significantly improved total cholesterol (TC, WMD = -0.22; 95% CI: -0.32∼ -0.11), triglyceride (TG,WMD = -0.36; 95% CI: -0.48∼-0.25), high-density lipoprotein cholesterol (HDL-C,WMD = 0.05; 95% CI: 0.02∼ 0.08), hemoglobin A1c (HbA1c, WMD = -0.19; 95% CI: -0.31∼-0.06) and C-reactive protein (CRP,WMD = -0.40; 95% CI: -0.74∼-0.07) levels compared to controls (p < 0.05). There was no significant effect on renal function, fasting blood sugar (FBS), insulin resistance (HOMA-IR), low-density lipoprotein cholesterol (LDL-C), adiponectin and leptin (p > 0.05).

Conclusions

: The results of this systematic review suggest that n-3 PUFAs can improve cardiovascular risk factors in type 2 diabetes.

Bone remodeling is precisely regulated mainly by osteoblasts and osteoclasts. Although some G-protein coupled receptors (GPCRs) were reported to play roles in osteoblast function, little is known about the roles in osteoclasts. In this study, we found, for the first time, that the expression of GPR110 increased during osteoclastogenesis. GPR110 belongs to adhesion GPCR and was the functional receptor of N-docosahexaenoyl ethanolamine (also called synaptamide). Synaptamide suppressed osteoclastogenesis induced by receptor activator of nuclear factor-kappa B ligand. Considering that synaptamide is the endogenous metabolite of DHA, we hypothesized that DHA may inhibit osteoclastogenesis by affecting synaptamide/GPR110 signaling. But GPR110 knockout and subsequent rescue experiments revealed a pivotal role of GPR110 in the attenuation of osteoclastogenesis by synaptamide but not by DHA. These results suggest that synaptamide/GPR110 signaling negatively regulates osteoclastogenesis. Our study suggested that ligands of GPR110, such as synaptamide, might be a useful drug for osteoporotic patients.

Prostanoids are potent inflammatory mediators that play a regulatory role in the innate immune activation of the adaptive immune response to determine the duration of protection against infection. We aim to quantify the modulation of prostanoids profiles in lipopolysaccharide (LPS)–stimulated THP-1 cells treated with the novel pertussis antigen BscF. We compared the effect with pertussis antigens present in the current Tdap vaccine to understand the immunomodulatory effect that might contribute to the diminished Tdap vaccine effectiveness. The inflammatory challenge with LPS induced a robust elevation of most prostanoid family members compared to the control treatment. Treatment with BscF and Tdap significantly reduced the LPS-stimulated elevation of prostaglandins (PGs) D2, E2, and F2α, as well as thromboxane (TX) A2 levels. An opposite trend was observed for PGI2, as both antigens accelerated the LPS-stimulated upregulation. Further, we quantified cyclooxygenases (COXs) that catalyze the biosynthesis of prostanoids and found that both antigens significantly reduced LPS-stimulated COX-1 and COX-2, demonstrating that the waning of acellular pertussis vaccines’ protective immunity may be due to other downstream enzymes not related to COXs. Our present study validates the potential role of BscF as an adjuvant, resulting in the next-generation pertussis vaccine discovery.

The omega-3 fatty acids (n3-FAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) rapidly incorporate into cell membranes where they modulate signal transduction pathways, lipid raft formation, and cholesterol distribution. Membrane n3-FAs also form specialized pro-resolving mediators and other intracellular oxylipins that modulate inflammatory pathways, including T-cell differentiation and gene expression. Cardiovascular (CV) trials have shown that EPA, administered as icosapent ethyl (IPE), reduces composite CV events, along with plaque volume, in statin-treated, high-risk patients. Mixed EPA/DHA regimens have not shown these benefits, perhaps as the result of differences in formulation, dosage, or potential counter-regulatory actions of DHA. Indeed, EPA and DHA have distinct, tissue-specific effects on membrane structural organization and cell function. This review summarizes: (1) results of clinical outcome and imaging trials using n3-FA formulations; (2) membrane interactions of n3-FAs; (3) effects of n3-FAs on membrane oxidative stress and cholesterol crystalline domain formation during hyperglycemia; (4) n3-FA effects on endothelial function; (5) role of n3-FA-generated metabolites in inflammation; and (6) ongoing and future clinical investigations exploring treatment targets for n3-FAs, including COVID-19.

Polyunsaturated fatty acids (PUFA) play essential roles in cell membrane structure and physiological processes including signal transduction, cellular metabolism and tissue homeostasis to combat diseases. PUFA are either consumed from food or synthesized by enzymatic desaturation, elongation and peroxisomal β-oxidation. The nutritionally essential precursors α-linolenic acid (C18:3n-3; ALA) and linoleic acid (C18:2n-6; LA) are subjected to desaturation by Δ6D/Δ5D desaturases and elongation by elongases 2/5, enzymes that are induced by insulin and repressed by PUFA. Maintaining an optimally low n-6/n-3 PUFA ratio is linked to prevention of the development of several diseases, including nonalcoholic fatty liver disease (NAFLD) that is characterized by depletion of PUFA promoting hepatic steatosis and inflammation. In this context, supplementation with n-3 PUFA revealed significant lowering of hepatic steatosis in obese patients, whereas prevention of fatty liver by high-fat diet in mice is observed in n-3 PUFA and hydroxytyrosol co-administration. The aim of this work is to review the role of nutritional status and nutrient availability on markers of PUFA biosynthesis. In addition, the impact of oxidative stress developed as a result of NAFLD, a redox imbalance that may alter the expression and activity of the enzymes involved, and diminished n-3 PUFA levels by free-radical dependent peroxidation processes will be discussed.

Evidence suggests antioxidant and anti-inflammatory properties of omega-3 polyunsaturated fatty acids (n-3 PUFA). However, the effect of supplementation of this fatty acid profile on the telomere length and the telomerase enzyme activity was not revised yet. The PubMed and Embase® databases were used to search for clinical trials. A total of six clinical trials were revised. Omega-3 PUFA supplementation did not statistically affect telomere length in three out of three studies but affected telomerase activity in two out of four studies. The supplementation increased telomerase enzyme activity in subjects with first-episode schizophrenia. Besides, it decreased telomerase enzyme activity without modulating the effects of Pro12Ala polymorphism on the PPARγ gene in type 2 diabetes subjects. The methodological differences between the studies and the limited number of studies on the theme suggest that further studies are needed to elucidate the effects of n-3 PUFA supplementation on telomere length and telomerase enzyme activity in humans.