The seeds of
(horseradish tree) contain about 40% of one of the most stable vegetable oils (Moringa seed oil). Therefore, the effects of Moringa seed oil on human SZ95 sebocytes were investigated and ...were compared with other vegetable oils. Immortalized human SZ95 sebocytes were treated with Moringa seed oil, olive oil, sunflower oil, linoleic acid and oleic acid. Lipid droplets were visualized by Nile Red fluorescence, cytokine secretion via cytokine antibody array, cell viability with calcein-AM fluorescence, cell proliferation by real-time cell analysis, and fatty acids were determined by gas chromatography. Statistical analysis was performed by the Wilcoxon matched-pairs signed-rank test, the Kruskal-Wallis test and Dunn's multiple comparison test. The vegetable oils tested stimulated sebaceous lipogenesis in a concentration-dependent manner. The pattern of lipogenesis induced by Moringa seed oil and olive oil was comparable to lipogenesis stimulated by oleic acid with also similar fatty acid secretion and cell proliferation patterns. Sunflower oil induced the strongest lipogenesis among the tested oils and fatty acids. There were also differences in cytokine secretion, induced by treatment with different oils. Moringa seed oil and olive oil, but not sunflower oil, reduced the secretion of pro-inflammatory cytokines, in comparison to untreated cells, and exhibited a low n-6/n-3 index. The anti-inflammatory oleic acid detected in Moringa seed oil probably contributed to its low levels of pro-inflammatory cytokine secretion and induction of cell death. In conclusion, Moringa seed oil seems to concentrate several desired oil properties on sebocytes, such as high content level of the anti-inflammatory fatty acid oleic acid, induction of similar cell proliferation and lipogenesis patterns compared with oleic acid, lipogenesis with a low n-6/n-3 index and inhibition of secretion of pro-inflammatory cytokines. These properties characterize Moringa seed oil as an interesting nutrient and a promising ingredient in skin care products.
Long-chain n-3 polyunsaturated fatty acid (PUFA) supplementation has shown potential benefits in the prevention of coronary heart disease (CHD); however, the impact of omega-3 fatty acid levels on ...CHD risk remains a subject of debate. Here, we aimed to investigate the association between n-3 PUFA levels and the risk of CHD, with particular reference to the subtypes of n-3 PUFA. Methods: Prospective studies and retrospective case-control studies analyzing n-3 PUFA levels in CHD, published up to 30 July 2022, were selected. A random effects meta-analysis was used for pooled assessment, with relative risks (RRs) expressed as 95% confidence intervals (CIs) and standardized mean differences expressed as weight mean differences (WMDs). Subgroup and meta-regression analyses were conducted to assess the impact of n-3 PUFA exposure interval on the CHD subtype variables of the study. Results: We included 20 prospective studies (cohort and nested case-control) and 16 retrospective case-control studies, in which n-3 PUFAs were measured. Higher levels of n-3 PUFAs (ALA, EPA, DPA, DHA, EPA + DHA, total n-3 PUFAs) were associated with a reduced risk of CHD, with RRs (95% CI) of 0.89 (0.81, 0.98), 0.83 (0.72, 0.96); 0.80 (0.67,0.95), 0.75 (0.64, 0.87), 0.83 (0.73, 0.95), and 0.80 (0.70, 0.93), respectively, p < 0.05. CHD patients had significantly lower n-3 PUFA levels compared to healthy controls (p < 0.05). In the subgroup analysis, a significant inverse trend was found for both fatal CHD and non-fatal CHD with n-3 PUFA (EPA + DHA) levels. Also, the link between n-3 PUFA levels in erythrocytes with total CHD was generally stronger than other lipid pools. Conclusions: n-3 PUFAs are significantly related to CHD risk, and these findings support the beneficial effects of n-3 PUFAs on CHD.
Colorectal cancer (CRC) is one of the most prevalent cancers worldwide, ranking as the third most malignant. The incidence of CRC has been increasing with time, and it is reported that Westernized ...diet and lifestyle play a significant role in its higher incidence and rapid progression. The intake of high amounts of omega-6 (
- 6) PUFAs and low levels of omega-3 (
- 3) PUFAs has an important role in chronic inflammation and cancer progression, which could be associated with the increase in CRC prevalence. Oxylipins generated from PUFAs are bioactive lipid mediators and have various functions, especially in inflammation and proliferation. Carcinogenesis is often a consequence of chronic inflammation, and evidence has shown the particular involvement of
- 6 PUFA arachidonic acid-derived oxylipins in CRC, which is further described in this review. A deeper understanding of the role and metabolism of PUFAs by their modifying enzymes, their pathways, and the corresponding oxylipins may allow us to identify new approaches to employ oxylipin-associated immunomodulation to enhance immunotherapy in cancer. This paper summarizes oxylipins identified in the context of the initiation, development, and metastasis of CRC. We further explore CRC chemo-prevention strategies that involve oxylipins as potential therapeutics.
Objective
Dyslipidemia, in particular elevated triglycerides (TGs) contribute to increased cardiovascular risk in type 2 diabetes mellitus (T2DM). In this pilot study we aimed to assess how increased ...TGs affect hepatic fat as well as polyunsaturated fatty acid (PUFA) metabolism and oxylipin formation in T2DM patients.
Methods
40 patients with T2DM were characterized analyzing routine lipid blood parameters, as well as medical history and clinical characteristics. Patients were divided into a hypertriglyceridemia (HTG) group (TG ≥ 1.7mmol/l) and a normal TG group with TGs within the reference range (TG < 1.7mmol/l). Profiles of PUFAs and their oxylipins in plasma were measured by gas chromatography and liquid chromatography/tandem mass spectrometry. Transient elastography (TE) was used to assess hepatic fat content measured as controlled attenuation parameter (CAP) (in dB/m) and the degree of liver fibrosis measured as stiffness (in kPa).
Results
Mean value of hepatic fat content measured as CAP as well as body mass index (BMI) were significantly higher in patients with high TGs as compared to those with normal TGs, and correlation analysis showed higher concentrations of TGs with increasing CAP and BMI scores in patients with T2DM. There were profound differences in plasma oxylipin levels between these two groups. Cytochrome P450 (CYP) and lipoxygenase (LOX) metabolites were generally more abundant in the HTG group, especially those derived from arachidonic acid (AA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), γ-linolenic acid (γ-LA), and α-linolenic acid (α-LA), and a strong correlation between TG levels and plasma metabolites from different pathways was observed.
Conclusions
In adult patients with T2DM, elevated TGs were associated with increased liver fat and BMI. Furthermore, these patients also had significantly higher plasma levels of CYP- and LOX- oxylipins, which could be a novel indicator of increased inflammatory pathway activity, as well as a novel target to dampen this activity.
Coronary artery disease (CAD) is the leading cause of death worldwide. Statins reduce morbidity and mortality of CAD. Intake of n-3 polyunsaturated fatty acid (n-3 PUFAs), particularly ...eicosapentaenoic acid (EPA), is associated with reduced morbidity and mortality in patients with CAD. Previous data indicate that a higher conversion of precursor fatty acids (FAs) to arachidonic acid (AA) is associated with increased CAD prevalence. Our study explored the FA composition in blood to assess n-3 PUFA levels from patients with and without CAD. We analyzed blood samples from 273 patients undergoing cardiac catheterization. Patients were stratified according to clinically relevant CAD (
= 192) and those without (
= 81). FA analysis in full blood was performed by gas chromatography. Indicating increased formation of AA from precursors, the ratio of dihomo-gamma-linolenic acid (DGLA) to AA, the delta-5 desaturase index (D5D index) was higher in CAD patients. CAD patients had significantly lower levels of omega-6 polyunsaturated FAs (n-6 PUFA) and n-3 PUFA, particularly EPA, in the blood. Thus, our study supports a role of increased EPA levels for cardioprotection.
In spite of therapeutic improvements in the treatment of different hematologic malignancies, the prognosis of acute myeloid leukemia (AML) treated solely with conventional induction and consolidation ...chemotherapy remains poor, especially in association with high risk chromosomal or molecular aberrations. Recent discoveries describe the complex interaction of immune effector cells, as well as the role of the bone marrow microenvironment in the development, maintenance and progression of AML. Lipids, and in particular omega-3 as well as omega-6 polyunsaturated fatty acids (PUFAs) have been shown to play a vital role as signaling molecules of immune processes in numerous benign and malignant conditions. While the majority of research in cancer has been focused on the role of lipid mediators in solid tumors, some data are showing their involvement also in hematologic malignancies. There is a considerable amount of evidence that AML cells are targetable by innate and adaptive immune mechanisms, paving the way for immune therapy approaches in AML. In this article we review the current data showing the lipid mediator and lipidome patterns in AML and their potential links to immune mechanisms.
Hepatocellular carcinoma (HCC) is a leading cause of cancer death. The multikinase inhibitor sorafenib is widely used for systemic therapy in advanced HCC. Sorafenib might affect epoxyeicosanoids, as ...it is also a potent inhibitor of the soluble epoxide hydrolase (sEH), which catalyzes the conversion of epoxides derived from long-chain polyunsaturated fatty acids (PUFAs), such as arachidonic acid (AA) and omega-3 docosahexaenoic acid (DHA), into their corresponding diols. Experimental studies with AA-derived epoxyeicosatrienoic acids (EETs) showed that they can promote tumor growth and metastasis, while DHA-derived 19,20-epoxydocosapentaenoic acid (19,20-EDP) was shown to have anti-tumor activity in mice. In this pilot study, we assessed the effect of sorafenib treatment on the presence of lipid mediators, such as EETs, in blood of the patients with HCC using the lipidomics technology. We found a significant increase in 11,12-EET and 14,15-EET levels in HCC patients treated with sorafenib. Furthermore, while not significant in this small sample set, the data presented indicate that sorafenib can also increase the level of omega-3 DHA-derived 19,20-EDP. While the effect on EETs might hamper the anti-tumor effect of sorafenib, we hypothesize that supplementation of DHA in sorafenib-treated HCC patients could increase the level of 19,20-EDP and thereby enhance its anti-tumor effect.
Inflammatory bowel disease (IBD) is an immune-mediated gut dysfunction, which might also be associated with an inflammatory phenotype in the liver. It is known that the nutritional intake of omega-3 ...polyunsaturated fatty acids (n-3 PUFA) is inversely correlated to the severity and occurrence of IBD. In order to investigate whether n-3 PUFA can also reduce liver inflammation and oxidative liver damage due to colon inflammation, we explored the dextran sulfate sodium (DSS)-induced colitis model in wild-type and fat-1 mice with endogenously increased n-3 PUFA tissue content. Besides confirming previous data of alleviated DSS-induced colitis in the fat-1 mouse model, the increase of n-3 PUFA also resulted in a significant reduction of liver inflammation and oxidative damage in colitis-affected fat-1 mice as compared to wild-type littermates. This was accompanied by a remarkable increase of established inflammation-dampening n-3 PUFA oxylipins, namely docosahexaenoic acid-derived 19,20-epoxydocosapentaenoic acid and eicosapentaenoic acid-derived 15-hydroxyeicosapentaenoic acid and 17,18-epoxyeicosatetraenoic acid. Taken together, these observations demonstrate a strong inverse correlation between the anti-inflammatory lipidome derived from n-3 PUFA and the colitis-triggered inflammatory changes in the liver by reducing oxidative liver stress.
Hepatocellular carcinoma (HCC) is a leading cause of cancer death, and medical treatment options are limited. The multikinase inhibitor sorafenib was the first approved drug widely used for systemic ...therapy in advanced HCC. Sorafenib might affect polyunsaturated fatty acids (PUFA)-derived epoxygenated metabolite levels, as it is also a potent inhibitor of the soluble epoxide hydrolase (sEH), which catalyzes the conversion of cytochrome-P450 (CYP)-derived epoxide metabolites derived from PUFA, such as omega-6 arachidonic acid (AA) and omega-3 docosahexaenoic acid (DHA), into their corresponding dihydroxy metabolites. Experimental studies with AA-derived epoxyeicosatrienoic acids (EETs) have shown that they can promote tumor growth and metastasis, while DHA-derived 19,20-epoxydocosapentaenoic acid (19,20-EDP) was shown to have anti-tumor activity in mice. In this study, we found a significant increase in EET levels in 43 HCC patients treated with sorafenib and a trend towards increased levels of DHA-derived 19,20-EDP. We demonstrate that the effect of sorafenib on CYP- metabolites led to an increase of 19,20-EDP and its dihydroxy metabolite, whereas DHA plasma levels decreased under sorafenib treatment. These data indicate that specific supplementation with DHA could be used to increase levels of the epoxy compound 19,20-EDP with potential anti-tumor activity in HCC patients receiving sorafenib therapy.
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