-
Molecules (Basel, Switzerland) Jun 2024Research over the last 25 years related to structural elucidations and biological investigations of the specialized pro-resolving mediators has spurred great interest in... (Review)
Review
Research over the last 25 years related to structural elucidations and biological investigations of the specialized pro-resolving mediators has spurred great interest in targeting these endogenous products in total synthesis. These lipid mediators govern the resolution of inflammation as potent and stereoselective agonists toward individual G-protein-coupled receptors, resulting in potent anti-inflammatory activities demonstrated in many human disease models. Specialized pro-resolving mediators are oxygenated polyunsaturated products formed in stereoselective and distinct biosynthetic pathways initiated by various lipoxygenase and cyclooxygenase enzymes. In this review, the reported stereoselective total synthesis and biological activities of the specialized pro-resolving mediators biosynthesized from the polyunsaturated fatty acid n-3 docosapentaenoic acid are presented.
Topics: Humans; Fatty Acids, Unsaturated; Animals; Prostaglandin-Endoperoxide Synthases; Anti-Inflammatory Agents; Inflammation
PubMed: 38930898
DOI: 10.3390/molecules29122833 -
Nutrients May 2024Long-chain -3 polyunsaturated fatty acid (PUFA) supplementation has shown potential benefits in the prevention of coronary heart disease (CHD); however, the impact of... (Meta-Analysis)
Meta-Analysis
UNLABELLED
Long-chain -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 -3 PUFA levels and the risk of CHD, with particular reference to the subtypes of -3 PUFA.
METHODS
Prospective studies and retrospective case-control studies analyzing -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 -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 -3 PUFAs were measured. Higher levels of -3 PUFAs (ALA, EPA, DPA, DHA, EPA + DHA, total -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, < 0.05. CHD patients had significantly lower -3 PUFA levels compared to healthy controls ( < 0.05). In the subgroup analysis, a significant inverse trend was found for both fatal CHD and non-fatal CHD with -3 PUFA (EPA + DHA) levels. Also, the link between -3 PUFA levels in erythrocytes with total CHD was generally stronger than other lipid pools.
CONCLUSIONS
-3 PUFAs are significantly related to CHD risk, and these findings support the beneficial effects of -3 PUFAs on CHD.
Topics: Humans; Fatty Acids, Omega-3; Coronary Disease; Observational Studies as Topic; Female; Retrospective Studies; Male; Case-Control Studies; Middle Aged; Prospective Studies; Dietary Supplements; Aged; Risk Factors
PubMed: 38892543
DOI: 10.3390/nu16111610 -
The Journal of Nutritional Biochemistry Jun 2024Females have higher docosahexaenoic acid (DHA) levels than males, proposed to be a result of higher DHA synthesis rates from α-linolenic acid (ALA). However, DHA...
Females have higher docosahexaenoic acid (DHA) levels than males, proposed to be a result of higher DHA synthesis rates from α-linolenic acid (ALA). However, DHA synthesis rates are reported to be low, and have not been directly compared between sexes. Here, we apply a new compound specific isotope analysis model to determine n-3 PUFA synthesis rates in male and female mice and assess its potential translation to human populations. Male and female C57BL/6N mice were allocated to one of three 12-week dietary interventions with added ALA, eicosapentaenoic acid (EPA) or DHA. The diets included low carbon-13 (δC)-n-3 PUFA for 4 weeks, followed by high δC-n-3 PUFA for 8 weeks (n=4 per diet, time point, sex). Following the diet switch, blood and tissues were collected at multiple time points, and fatty acid levels and δC were determined and fit to one-phase exponential decay modeling. Hepatic DHA synthesis rates were not different (p>0.05) between sexes. However, n-3 docosapentaenoic acid (DPAn-3) synthesis from dietary EPA was 66% higher (p<0.05) in males compared to females, suggesting higher synthesis downstream of DPAn-3 of females. Estimates of percent conversion of dietary ALA to serum DHA was 0.2%, in line with previous rodent and human estimates, but severely underestimates percent dietary ALA conversion to whole body DHA of 9.5%. Taken together, our data indicates that reports of low human DHA synthesis rates may be inaccurate, with synthesis being much higher than previously believed. Future animal studies and translation of this model to humans are needed for greater understanding of n-3 PUFA synthesis and metabolism, and whether the higher-than-expected ALA-derived DHA can offset dietary DHA recommendations set by health agencies.
PubMed: 38876393
DOI: 10.1016/j.jnutbio.2024.109689 -
Lipids in Health and Disease Jun 2024Exposure to different concentration levels of fatty acids (FAs) may have an impact on depression. However, previous studies using individual FAs may not reflect the...
BACKGROUND
Exposure to different concentration levels of fatty acids (FAs) may have an impact on depression. However, previous studies using individual FAs may not reflect the performance of mixtures of various FAs, and the associations of FA patterns with depression remain unclear.
METHODS
We conducted the cross-sectional analysis in 792 adults aged 18 and older with available serum FAs and depression screening data in the National Health and Nutrition Examination Survey (NHANES) 2011-2012. The serum concentrations of thirty FAs were measured using gas chromatography-mass spectrometry and their percentage compositions were subsequently calculated. Depression was defined as the Patient Health Questionnaire-9 score ≥ 10. We employed principal component analysis to derive serum FA patterns. We examined the association between these patterns and depression in the overall population and various subgroups through survey-weighted logistic regression.
RESULTS
Four distinct patterns of serum FAs were identified: 'high eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA); low docosatetraenoic acid (DTA) and docosapentaenoic acid (DPA) n-6', 'high long-chain saturated FA and long chain FA', 'low median-chain saturated FA and myristoleic acid' and 'low capric acid and lauric acid; high gamma-linolenic acid (GLA) and stearidonic acid (SDA)' pattern. Individuals in the high tertile of 'high EPA and DHA; low DTA and DPA n-6' pattern score had 0.46 (95% CI: 0.22, 0.93) lower odds of developing depression compared to individuals in the lowest tertile after adjusting for confounders such as age, sex, physical activity and total energy intake, etc. The odds ratio (OR) of depression was increased in the population with the highest tertile of 'low capric acid and lauric acid; high GLA and SDA' pattern (OR: 2.45, 95% CI: 1.24, 4.83). In subgroup analyses, we observed that the association between 'high EPA and DHA; low DTA and DPA n-6' and depression persisted among specific demographic and lifestyle subgroups, including females, non-Mexican Americans, non-obese, those aged over 60 years, smokers and drinkers. Similarly, 'low capric acid and lauric acid; high GLA and SDA' showed stable associations in female, non-Mexican Americans and smokers.
CONCLUSIONS
Serum FA patterns are associated with depression, and their relationships vary across sex, race, BMI, age, smoking and drinking subgroups, highlighting the importance of considering specific FA patterns within these demographic and lifestyle categories. Utilization of combined FA administration may serve as a mitigation measure against depression in these specific populations.
Topics: Humans; Female; Male; Depression; Adult; Middle Aged; Fatty Acids; Nutrition Surveys; Cross-Sectional Studies; United States; Decanoic Acids; Eicosapentaenoic Acid; Aged; Fatty Acids, Unsaturated; Young Adult; Adolescent; Principal Component Analysis
PubMed: 38851716
DOI: 10.1186/s12944-024-02142-9 -
Scientific Reports May 2024Arachidonic acid (C20: 4n-6, AA) plays a fundamental role in fish physiology, influencing growth, survival and stress resistance. However, imbalances in dietary AA can...
Arachidonic acid (C20: 4n-6, AA) plays a fundamental role in fish physiology, influencing growth, survival and stress resistance. However, imbalances in dietary AA can have detrimental effects on fish health and performance. Optimal AA requirements for rainbow trout have not been established. This study aimed to elucidate the effects of varying dietary AA levels on survival, growth, long-chain polyunsaturated fatty acid (LC-PUFA) biosynthetic capacity, oxylipin profiles, lipid peroxidation, and stress resistance of rainbow trout fry. Over a period of eight weeks, 4000 female rainbow trout fry at the resorptive stage (0.12 g) from their first feeding were fed diets with varying levels of AA (0.6%, 1.1% or 2.5% of total fatty acids) while survival and growth metrics were closely monitored. The dietary trial was followed by an acute confinement stress test. Notably, while the fatty acid profiles of the fish reflected dietary intake, those fed an AA-0.6% diet showed increased expression of elongase5, highlighting their inherent ability to produce LC-PUFAs from C18 PUFAs and suggesting potential AA or docosapentaenoic acid (DPA) biosynthesis. However, even with this biosynthetic capacity, the trout fed reduced dietary AA had higher mortality rates. The diet had no effect on final weight (3.38 g on average for the three diets). Conversely, increased dietary AA enhanced eicosanoid production from AA, suggesting potential inflammatory and oxidative consequences. This was further evidenced by an increase in non-enzymatic lipid oxidation metabolites, particularly in the AA-2.5% diet group, which had higher levels of phytoprostanes and isoprostanes, markers of cellular oxidative damage. Importantly, the AA-1.1% diet proved to be particularly beneficial for stress resilience. This was evidenced by higher post-stress turnover rates of serotonin and dopamine, neurotransmitters central to the fish's stress response. In conclusion, a dietary AA intake of 1.1% of total fatty acids appears to promote overall resilience in rainbow trout fry.
Topics: Animals; Oncorhynchus mykiss; Oxylipins; Arachidonic Acid; Fatty Acids, Unsaturated; Stress, Physiological; Female; Animal Feed; Diet; Lipid Peroxidation; Oxidative Stress
PubMed: 38811794
DOI: 10.1038/s41598-024-63173-x -
Journal of Clinical Medicine May 2024: Lipid metabolism plays an important role in maternal health and fetal development. There is a gap in the knowledge of how lipid metabolism changes during pregnancy for...
: Lipid metabolism plays an important role in maternal health and fetal development. There is a gap in the knowledge of how lipid metabolism changes during pregnancy for Black women who are at a higher risk of adverse outcomes. We hypothesized that the comprehensive lipidome profiles would show variation across pregnancy indicative of requirements during gestation and fetal development. : Black women were recruited at prenatal clinics. Plasma samples were collected at 8-18 weeks (T), 22-29 weeks (T), and 30-36 weeks (T) of pregnancy. Samples from 64 women who had term births (≥37 weeks gestation) were subjected to "shotgun" Orbitrap mass spectrometry. Mixed-effects models were used to quantify systematic changes and dimensionality reduction models were used to visualize patterns and identify reliable lipid signatures. : Total lipids and major lipid classes showed significant increases with the progression of pregnancy. Phospholipids and glycerolipids exhibited a gradual increase from T to T to T, while sphingolipids and total sterol lipids displayed a more pronounced increase from T to T. Acylcarnitines, hydroxy acylcarnitines, and Lyso phospholipid levels significantly decreased from T to T. A deviation was that non-esterified fatty acids decreased from T to T and increased again from T to T, suggestive of a potential role for these lipids during the later stages of pregnancy. The fatty acids showing this trend included key fatty acids-non-esterified Linoleic acid, Arachidonic acid, Alpha-linolenic acid, Eicosapentaenoic acid, Docosapentaenoic acid, and Docosahexaenoic acid. : Mapping lipid patterns and identifying lipid signatures would help develop intervention strategies to reduce perinatal health disparities among pregnant Black women.
PubMed: 38792337
DOI: 10.3390/jcm13102795 -
International Journal of Molecular... May 2024Disordered eating behavior differs between the restricting subtype (AN-R) and the binging and purging subtype (AN-BP) of anorexia nervosa (AN). Yet, little is known...
Disordered eating behavior differs between the restricting subtype (AN-R) and the binging and purging subtype (AN-BP) of anorexia nervosa (AN). Yet, little is known about how these differences impact fatty acid (FA) dysregulation in AN. To address this question, we analyzed 26 FAs and 7 FA lipogenic enzymes (4 desaturases and 3 elongases) in 96 women: 25 AN-R, 25 AN-BP, and 46 healthy control women. Our goal was to assess subtype-specific patterns. Lauric acid was significantly higher in AN-BP than in AN-R at the fasting timepoint ( = 0.038) and displayed significantly different postprandial changes 2 h after eating. AN-R displayed significantly higher levels of n-3 alpha-linolenic acid, stearidonic acid, eicosapentaenoic acid (EPA), docosapentaenoic acid, and n-6 linoleic acid and gamma-linolenic acid compared to controls. AN-BP showed elevated EPA and saturated lauric acid compared to controls. Higher EPA was associated with elevated anxiety in AN-R ( = 0.035) but was linked to lower anxiety in AN-BP ( = 0.043). These findings suggest distinct disordered eating behaviors in AN subtypes contribute to lipid dysregulation and eating disorder comorbidities. A personalized dietary intervention may improve lipid dysregulation and enhance treatment effectiveness for AN.
Topics: Humans; Female; Anorexia Nervosa; Adult; Fatty Acids; Young Adult; Lipogenesis; Eicosapentaenoic Acid; Lauric Acids; Fatty Acid Elongases; Adolescent; Fatty Acid Desaturases; Case-Control Studies; Fatty Acids, Unsaturated
PubMed: 38791555
DOI: 10.3390/ijms25105516 -
International Journal of Molecular... May 2024Oxylipins, the metabolites of polyunsaturated fatty acids, are vital in regulating cell proliferation and inflammation. Among these oxylipins, specialized pro-resolving...
Oxylipins, the metabolites of polyunsaturated fatty acids, are vital in regulating cell proliferation and inflammation. Among these oxylipins, specialized pro-resolving mediators notably contribute to inflammation resolution. Previously, we showed that the specialized pro-resolving mediators isomer 11,17dihydroxy docosapentaenoic acid (11,17diHDoPE) can be synthesized in bacterial cells and exhibits anti-inflammatory effects in mammalian cells. This study investigates the in vivo impact of 11,17diHDoPE in mice exposed to particulate matter 10 (PM10). Our results indicate that 11,17diHDoPE significantly mitigates PM10-induced lung inflammation in mice, as evidenced by reduced pro-inflammatory cytokines and pulmonary inflammation-related gene expression. Metabolomic analysis reveals that 11,17diHDoPE modulates inflammation-related metabolites such as threonine, 2-keto gluconic acid, butanoic acid, and methyl oleate in lung tissues. In addition, 11,17diHDoPE upregulates the LA-derived oxylipin pathway and downregulates arachidonic acid- and docosahexaenoic acid-derived oxylipin pathways in serum. Correlation analyses between gene expression and metabolite changes suggest that 11,17diHDoPE alleviates inflammation by interfering with macrophage differentiation. These findings underscore the in vivo role of 11,17diHDoPE in reducing pulmonary inflammation, highlighting its potential as a therapeutic agent for respiratory diseases.
Topics: Animals; Mice; Metabolome; Pneumonia; Particulate Matter; Anti-Inflammatory Agents; Fatty Acids, Unsaturated; Male; Lung; Mice, Inbred C57BL; Oxylipins; Metabolomics; Cytokines; Gene Expression Regulation
PubMed: 38791399
DOI: 10.3390/ijms25105360 -
Kidney Diseases (Basel, Switzerland) Apr 2024Unsaturated fatty acids play an essential role in the progression of diabetic nephropathy (DN). However, previous studies were mainly focused on the role of individual...
INTRODUCTION
Unsaturated fatty acids play an essential role in the progression of diabetic nephropathy (DN). However, previous studies were mainly focused on the role of individual unsaturated fatty acid. The serum unsaturated fatty acid patterns (FAPs) in patients with DN remain to be determined.
METHODS
A total of 135 patients with DN (DN group) and 322 patients with type II diabetes without nephropathy (non-DN group) were included in this study. Clinical data, serum levels of unsaturated fatty acids, and other laboratory indicators were collected. Multivariate logistic regression was applied to identify risk factors for serum unsaturated fatty acid level in both groups. Serum unsaturated fatty acids were subjected to factor analysis to identify distinct FAPs. Multivariable logistic regression was employed to assess the risk of DN associated with different serum FAPs.
RESULTS
After adjusting for confounders, three types of unsaturated fatty acid including C20:5 (eicosapentaenoic acid [EPA]), C22:6 (docosahexaenoic acid [DHA]), and C22:5 -3 (docosapentaenoic acid -3) were significantly associated with DN in the population. The odds ratios (ORs) (95% confidence interval [CI]) of DN were 0.583 (0.374, 0.908), 0.826 (0.716, 0.954), and 0.513 (0.298, 0.883), respectively. Factor analysis revealed five major FAPs, among which FAP2 (enriched with EPA and DHA) exhibited a significant inverse association with DN. In the multivariate-adjusted model, the OR (95% CI) was 0.678 (0.493, 0.933). Additionally, a combination of DHA and EPA enriched in FAP2 further decreased extracellular matrix production induced by transforming growth factor beta 1 in podocytes and tubular cells.
CONCLUSIONS
Our findings suggest that FAP2 which is enriched with DHA and EPA is associated with a reduced risk of DN. This highlights the potential of targeting FAP2 for the patients with DN.
PubMed: 38751794
DOI: 10.1159/000536532 -
BMC Musculoskeletal Disorders May 2024Synovitis, characterized by inflammation of the synovial membrane, is commonly induced by meniscus tears. However, significant differences in inflammatory responses and...
BACKGROUND
Synovitis, characterized by inflammation of the synovial membrane, is commonly induced by meniscus tears. However, significant differences in inflammatory responses and the key inflammatory mediators of synovium induced by different types of meniscal tears remain unclear.
METHODS
Magnetic resonance imaging (MRI) was employed to identify the type of meniscus tear, and the quantification of synovial inflammation was assessed through H&E staining assay. Transcription and expression levels of IL-1β and IL-6 were evaluated using bioinformatics, ELISA, RT-qPCR, and IHC of CD68 staining assays. The therapeutic potential of Docosapentaenoic Acid (DPA) was determined through network pharmacology, ELISA, and RT-qPCR assays. The safety of DPA was assessed using colony formation and EdU staining assays.
RESULTS
The results indicate that both IL-1β and IL-6 play pivotal roles in synovitis pathogenesis, with distinct expression levels across various subtypes. Among tested meniscus tears, oblique tear and bucket handle tear induced the most severe inflammation, followed by radial tear and longitudinal tear, while horizontal tear resulted in the least inflammation. Furthermore, in synovial inflammation induced by specific meniscus tears, the anterior medial tissues exhibited significantly higher local inflammation than the anterior lateral and suprapatellar regions, highlighting the clinical relevance and practical guidance of anterior medial tissues' inflammatory levels. Additionally, we identified the essential omega-3 fatty acid DPA as a potential therapeutic agent for synovitis, demonstrating efficacy in blocking the transcription and expression of IL-1β and IL-6 with minimal side effects.
CONCLUSION
These findings provide valuable insights into the nuanced nature of synovial inflammation induced by various meniscal tear classifications and contribute to the development of new adjunctive therapeutic agents in the management of synovitis.
Topics: Tibial Meniscus Injuries; Synovitis; Magnetic Resonance Imaging; Synovial Membrane; Humans; Fatty Acids, Unsaturated; Male; Interleukin-1beta; Animals; Interleukin-6; Female; Menisci, Tibial; Mice; Disease Models, Animal
PubMed: 38734632
DOI: 10.1186/s12891-024-07491-1