Adrenic Acid-Derived Epoxy Fatty Acids Are Naturally Occurring Lipids and Their Methyl Ester Prodrug Reduces Endoplasmic Reticulum Stress and Inflammatory Pain

Singh, Nalin; Barnych, Bogdan; Wagner, Karen; Wan, Debin; Morisseau, Christophe; Hammock, Bruce D.

doi:10.1021/acsomega.1c00241

Cited by 23 publications

(14 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Adrenic acid, the immediate precursor derived from arachidonic acid, is necessary for neuronal development and enrichment of myelinic lipids ( 63 , 64 ). Adrenic acid is metabolized by cytochrome P450s to a group of epoxy fatty acids and epoxyeicosatrienoic acids, which are the vital lipid mediators playing key role in exerting analgesia and reducing endoplasmic reticulum stress ( 65 ). Furthermore, functional studies showed that adrenic acid potently inhibited the formation of the chemoattractant leukotriene B4 (LTB4), which has been proposed as a contributor for chronic neuroinflammatory effects ( 66 – 68 ).…”

Section: Discussionmentioning

confidence: 99%

Causal effects of fatty acids on depression: Mendelian randomization study

Zeng

Wang³

et al. 2022

Front. Nutr.

View full text Add to dashboard Cite

ObjectivesFatty acids (FA) are widely believed to play a role in the pathophysiology of depression. However, the causal relationships between FA and depression remain elusive and warrant further research. We aimed to investigate the potential causal relationship between FA [saturated fatty acids (SFA), mono-unsaturated fatty acids (MUFA), and polyunsaturated fatty acids (PUFA)] and the risk of depression using Mendelian randomization (MR) analysis.MethodsWe conducted a two-sample MR analysis using large-scale European-based genome-wide association studies (GWASs) summary data related to depression (n = 500,199 individuals) and FA [saturated fatty acids (SFA), mono-unsaturated fatty acids (MUFA), and polyunsaturated fatty acids (PUFA)] levels. MR analysis was performed using the Wald ratio and inverse variance-weighted (IVW) methods, and sensitivity analysis was conducted by the simple mode, weighted mode, weighted median method, and MR-Egger method.ResultsWe found the causal effects for the levels of oleic acid (OA; OR = 1.07, p = 5.72 × 10–4), adrenic acid (OR = 0.74, p = 1.01 × 10–3), α-linolenic acid (ALA; OR = 2.52, p = 1.01 × 10–3), eicosapentaenoic acid (EPA; OR = 0.84, p = 3.11 × 10–3) on depression risk, after Bonferroni correction. The sensitivity analyses indicated similar trends. No causal effect between the levels of SFA and depression risk was observed.ConclusionOur study suggests that adrenic acid and EPA are protective against the risk of depression, while OA and ALA are potential risk factors for depression. Nonetheless, the underlying mechanisms that mediate the association between these FAs and depression risk should be investigated in further experiments.

show abstract

Section: Discussionmentioning

confidence: 99%

Causal effects of fatty acids on depression: Mendelian randomization study

Zeng

Wang³

et al. 2022

Front. Nutr.

View full text Add to dashboard Cite

show abstract

“…Adrenic acid (ADA; 22:4 ω 6) is an ω-6 FA more concentrated in liver, vasculature, kidney, adrenal gland, and brain. It can be converted into arachidonic acid through β-oxidation, which play an important role in inflammatory responses 57 , 59 , 60 . The plasma ADA concentration increases in humans and mice affected by nonalcoholic fatty liver disease.…”

Section: Discussionmentioning

confidence: 99%

Changes in plasma fatty acids profile in hyperketonemic ewes during early lactation: a preliminary study

Lisuzzo

Fiore

Harvatine

et al. 2022

Sci Rep

View full text Add to dashboard Cite

The transition from late pregnancy to early lactation is characterized by marked changes in energy balance of dairy ruminants. The mobilization of adipose tissue led to an increase in plasma non-esterified fatty acids (NEFA) and β-hydroxybutyrate (BHB). The aim of this study was to analyze the total plasma fatty acids of healthy and hyperketonemic dairy ewes in early lactation through gas chromatography (GC) to evaluate metabolic alterations. An observational study was used with a cross-sectional experimental design. Forty-six Sarda dairy ewes were enrolled in the immediate post-partum (7 ± 3 days in milk) and divided into two groups according to serum BHB concentration: non-hyperketonemic group (n = 28; BHB < 0.86 mmol/L) and hyperketonemic group (n = 18; BHB ≥ 0.86 mmol/L). A two-way ANOVA included the effect of group and parity was used to evaluate differences in fatty acids (FA) concentrations. A total of 34 plasma FA was assessed using GC. 12 out of 34 FA showed a significant different between groups and 3 out of 34 were tended to significance. Only NEFA concentration and stearic acid were influenced by parity. The results may suggest possible links with lipid metabolism, inflammatory and immune responses in hyperketonemic group. In conclusion, GC represents a useful tool in the study of hyperketonemia and primiparous dairy ewes might show a greater risk to develop this condition.

show abstract

“…DiHODE is a degradation compound of epoxy-fatty acid 50 , which is positively associated with inflammation in other studies 51 . Since epoxide hydrolases can generate DiHODE from the corresponding epoxy-fatty acid 52 , this enzyme might be important in mediating the influences from lifestyle factors to cancer. DiHODE is also an oxylipin, which is influenced by a high fat diet 53 .…”

Section: Amn Identifies Inflammation Linking Lifestyle Factors To Bre...mentioning

confidence: 99%

Active molecular network discovery links lifestyle variables to breast cancer in the Long Island Breast Cancer Study Project

Dolios

et al. 2022

Preprint

View full text Add to dashboard Cite

Background/Aim: Healthy lifestyle has been associated with decreased risk of developing breast cancer. Using untargeted metabolomics profiling, which provides unbiased information regarding lifestyle choices such as diet and exercise, we aim to identify the molecular mechanisms connecting lifestyle and breast cancer through network analysis. Methods: A total of 100 post-menopausal women, 50 with breast cancer and 50 cancer-free controls were selected from the Long Island Breast Cancer Study Project (LIBCSP). We measured untargeted plasma metabolomics using liquid chromatography-high resolution mass spectrometry (LC-HRMS). Using the ‘enet’ package, we retained highly correlated metabolites representing active molecular network (AMN) clusters for analysis. A typical machine learning workflow (LASSO) was used to examine associations between cancer status and AMN metabolites and covariates such as BMI, age, and reproductive factors. LASSO was then repeated to examine associations between AMN metabolites and 10 lifestyle related variables including smoking, physical activity, alcohol consumption, meat consumption, fruit and vegetables consumption, and supplemental vitamin use. Results were displayed as a network to uncover biological pathways linking lifestyle factors to breast cancer status. Results: After filtering, there were 1797 metabolomics peaks in the plasma samples. Of these, 851 “active” metabolites were retained in 197 correlation AMN clusters. Using LASSO, breast cancer status was associated with 71 “active” metabolites. Several of these metabolites were associated with lifestyle variables including meat consumption, alcohol consumption, and supplemental β-carotene, B12 and folate use. No individual lifestyle factors were significantly associated with breast cancer status using LASSO, suggesting that metabolites may act as biological intermediaries between healthy lifestyle factors and breast cancer. In particular, DiHODE, a metabolite linked with inflammation, was associated with breast cancer status and connected to β-carotene supplement usage through an AMN. Conclusions: We found several plasma metabolites associated with lifestyle factors and breast cancer status. Future studies investigating the mechanistic role of inflammation in linking supplement usage to breast cancer status are warranted.

show abstract

Adrenic Acid-Derived Epoxy Fatty Acids Are Naturally Occurring Lipids and Their Methyl Ester Prodrug Reduces Endoplasmic Reticulum Stress and Inflammatory Pain

Cited by 23 publications

References 43 publications

Causal effects of fatty acids on depression: Mendelian randomization study

Causal effects of fatty acids on depression: Mendelian randomization study

Changes in plasma fatty acids profile in hyperketonemic ewes during early lactation: a preliminary study

Active molecular network discovery links lifestyle variables to breast cancer in the Long Island Breast Cancer Study Project

Contact Info

Product

Resources

About