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International Journal of Molecular... Feb 2024Retinitis pigmentosa (RP) is a retinal degenerative disease associated with a diversity of genetic mutations. In a natural progression study (NPS) evaluating the...
Retinitis pigmentosa (RP) is a retinal degenerative disease associated with a diversity of genetic mutations. In a natural progression study (NPS) evaluating the molecular changes in Royal College of Surgeons (RCS) rats using lipidomic profiling, RNA sequencing, and gene expression analyses, changes associated with retinal degeneration from p21 to p60 were evaluated, where reductions in retinal expression corresponded with disease progression. This important enzyme catalyzes the formation of specialized pro-resolving mediators (SPMs) such as lipoxins (LXs), resolvins (RvDs), and docosapentaenoic acid resolvins (DPA RvDs), where reduced corresponded with reduced SPMs. Retinal DPA RvD2 levels were found to correlate with retinal structural and functional decline. Retinal RNA sequencing comparing p21 with p60 showed an upregulation of microglial inflammatory pathways accompanied by impaired damage-associated molecular pattern (DAMP) clearance pathways. This analysis suggests that ALXR/FPR2 activation can ameliorate disease progression, which was supported by treatment with an LXA4 analog, NAP1051, which was able to promote the upregulation of and . This study showed that retinal inflammation from activated microglia and dysregulation of lipid metabolism were central to the pathogenesis of retinal degeneration in RP, where ALXR/FPR2 activation was able to preserve retinal structure and function.
Topics: Animals; Humans; Rats; Arachidonate 15-Lipoxygenase; Disease Models, Animal; Disease Progression; Retina; Retinal Degeneration; Retinitis Pigmentosa
PubMed: 38396985
DOI: 10.3390/ijms25042309 -
Ecotoxicology and Environmental Safety Jan 2024Nickel oxide nanoparticles (NiONPs) are toxic heavy metal compounds that induce liver fibrosis and metabolic disorders. Current research shows that the intestinal...
Nickel oxide nanoparticles (NiONPs) are toxic heavy metal compounds that induce liver fibrosis and metabolic disorders. Current research shows that the intestinal microbiota regulates liver metabolism through the gut-liver axis. However, it is unclear whether NiONPs affect the intestinal microbiota and the relationship between microbiota and liver metabolic disorders. Therefore, in this study, we established liver fibrosis model by administering 0.015, 0.06 and 0.24 mg/mL NiONPs through tracheal instillation twice a week for 9 weeks in rats, then we collected serum and fecal sample for whole metabolomics and metagenomic sequencing. As the result of sequencing, we screened out seven metabolites (beta-D-glucuronide, methylmalonic acid, linoleic acid, phosphotidylcholine, lysophosphatidylinositol, docosapentaenoic acid and progesterone) that related to functional alterations (p < 0.05), and obtained a decrease of probiotics abundances (p < 0.05) as well as a variation of the microbiota enzyme activity (p < 0.05), indicating that NiONPs inhibited the proliferation of probiotics. As the result of correlation analysis, we found a positive correlation between differential metabolites and probiotics, such as lysophosphatidylinositol was positively correlated with Desulfuribacillus, Jeotgallibacillus and Rummeliibacillus (p < 0.05). We also found that differential metabolites had correlations with differential proteins and enzymes of intestinal microbiota, such as glucarate dehydratase, dihydroorotate dehydrogenase and acetyl-CoA carboxylase (p < 0.05). Finally, we screened six metabolic pathways with both differential intestinal microbiota enzymes and metabolites were involved, such as pentose and glucuronate interconversions, and linoleic acid metabolism. In vitro experiments showed that NiONPs increased the transcriptional expression of Col1A1 in LX-2 cells, while reducing the mRNA expression of serine/threonine activators, acetyl coenzyme carboxylase, and lysophosphatidylinositol synthase, and short chain fatty acid sodium butyrate can alleviate these variation trends. The results proved that the intestinal microbiota enzyme systems were associated with serum metabolites, suggesting that the disturbance of intestinal microbiota and reduction of probiotics promoted the occurrence and development of NiONPs-induced liver fibrosis by affecting metabolic pathways.
Topics: Rats; Animals; Gastrointestinal Microbiome; Linoleic Acid; Liver Cirrhosis; Acetyl-CoA Carboxylase; Metabolic Diseases
PubMed: 38194811
DOI: 10.1016/j.ecoenv.2024.115943 -
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 -
Animals : An Open Access Journal From... Dec 2023The purpose of our study was to investigate the effect of 0.35 mg Se/kg basal diet (BD) (Se as sodium selenate (Se) and yeast rich in seleno-methionine (Se)) and 0.1%...
The purpose of our study was to investigate the effect of 0.35 mg Se/kg basal diet (BD) (Se as sodium selenate (Se) and yeast rich in seleno-methionine (Se)) and 0.1% carnosic acid (CA) supplementation to the diet containing 1% fish oil (F-O) and 2% rapeseed oil (R-O) on the contents of fatty acids (FA), malondialdehyde (MDA), tocopherols (Ts), and total cholesterol (TCh) in lambs' spleens. A total of 24 male lambs (4 groups per 6 animals) have been fed: the control diet-the basal diet (BD) enriched in F-O and R-O; the CA diet-BD enriched in F-O, R-O, and CA; the SeCA diet-BD enriched in F-O, R-O, CA, and Se; the SeCA diet-BD enriched in F-O, R-O, CA, and Se. Dietary modifications affected the profiles of saturated (SFA), monounsaturated (MUFA), and polyunsaturated (PUFA) fatty acids in spleens. The SeCA and SeCA diets increased the docosapentaenoic acid preference in Δ4-desaturase; hence, a higher content of docosahexaenoic acid was found in the spleens of Se- or Se-treated lambs than in spleens of animals receiving the CA and control diets. The SeCA and SeCA diets increased the concentration ratio of n-3long-chain PUFA (n-3LPUFA) to FA (n-3LPUFA/FA) in spleens compared to the control and CA diets. The content of n-3PUFA was higher in the spleens of Se treated lambs than in spleens of animals receiving the SeCA, CA, and control diets. The SeCA diet increased the content of c9t11CLA in the spleen compared to the control, CA, and SeCA diets. Experimental diets reduced the level of atherogenic FA, the content ratios of n-6PUFA/n-3PUFA and n-6LPUFA/n-3LPUFA, and improved the content ratio of MUFA/FA and the value of the hypocholesterolemic/hypercholesterolemic FA ratio in the spleen in comparison with the control diet. The experimental diets supplemented with Se or Se increased levels of TCh and Ts in spleens in comparison with the CA and control CA diets. The present studies documented that Se, Se, and CA influenced the metabolism of FA, Ts, and cholesterol in spleens.
PubMed: 38200864
DOI: 10.3390/ani14010133 -
NPJ Biofilms and Microbiomes Jan 2024Omega-3 (n-3) polyunsaturated fatty acids (PUFAs), particularly docosahexaenoic acid (DHA), are required for the structure and function of the retina. Several...
Omega-3 (n-3) polyunsaturated fatty acids (PUFAs), particularly docosahexaenoic acid (DHA), are required for the structure and function of the retina. Several observational studies indicate that consumption of a diet with relatively high levels of n-3 PUFAs, such as those provided by fish oils, has a protective effect against the development of age-related macular degeneration. Given the accumulating evidence showing the role of gut microbiota in regulating retinal physiology and host lipid metabolism, we evaluated the potential of long-term dietary supplementation with the Gram-positive bacterium Lactobacillus helveticus strain VEL12193 to modulate the retinal n-3 PUFA content. A set of complementary approaches was used to study the impact of such a supplementation on the gut microbiota and host lipid/fatty acid (FA) metabolism. L. helveticus-supplementation was associated with a decrease in retinal saturated FAs (SFAs) and monounsaturated FAs (MUFAs) as well as an increase in retinal n-3 and omega-6 (n-6) PUFAs. Interestingly, supplementation with L. helveticus enriched the retina in C22:5n-3 (docosapentaenoic acid, DPA), C22:6n-3 (DHA), C18:2n-6 (linoleic acid, LA) and C20:3n-6 (dihomo gamma-linolenic acid, DGLA). Long-term consumption of L. helveticus also modulated gut microbiota composition and some changes in OTUs abundance correlated with the retinal FA content. This study provides a proof of concept that targeting the gut microbiota could be an effective strategy to modulate the retinal FA content, including that of protective n-3 PUFAs, thus opening paths for the design of novel preventive and/or therapeutical strategies for retinopathies.
Topics: Animals; Mice; Fatty Acids, Omega-3; Lactobacillus helveticus; Biological Availability; Diet; Retina
PubMed: 38238339
DOI: 10.1038/s41522-023-00474-5 -
MedRxiv : the Preprint Server For... Sep 2023Many questions remain unanswered regarding the implication of lipid metabolites in severe SARS-CoV-2 infections. By re-analyzed sequencing data from the nasopharynx of a...
BACKGROUND
Many questions remain unanswered regarding the implication of lipid metabolites in severe SARS-CoV-2 infections. By re-analyzed sequencing data from the nasopharynx of a previously published cohort, we found that genes, involved in eicosanoid synthesis, were up-regulated in high WHO score patients, especially in goblet cells. Herein, we aimed to further understand the roles played by eicosanoids during severe SARS-CoV-2 infection.
METHODS AND FINDINGS
We performed a total fatty acid panel on plasma and bulk RNA-seq analysis on peripheral blood mononuclear cells (PBMCs) collected from 10 infected and 10 uninfected patients. Univariate comparison of lipid metabolites revealed that lipid metabolites were increased in SARS-CoV-2 patients including the lipid mediators Arachidonic Acid (AA) and Eicosapentaenoic Acid (EPA). AA, EPA and the fatty acids Docosahexaenoic acid (DHA) and Docosapentaenoic acid (DPA), were positively correlated to WHO disease severity score. Transcriptomic analysis demonstrated that COVID-19 patients can be segregated based on WHO scores. Ontology, KEGG and Reactome analysis identified pathways enriched for genes related to innate immunity, interactions between lymphoid and nonlymphoid cells, interleukin signaling and, cell cycling pathways.
CONCLUSIONS
Our study offers an association between nasopharynx mucosa eicosanoid genes expression, specific serum inflammatory lipids and, subsequent DNA damage pathways activation in PBMCs to severity of COVID-19 infection.
PubMed: 37745424
DOI: 10.1101/2023.09.14.23295549 -
American Heart Journal Aug 2023Tissue levels of n-3 polyunsaturated fatty acids (PUFAs) have been inversely related with risk of myocardial infarction (MI). Whether ratios of n-3 to n-6 PUFAs,...
BACKGROUND
Tissue levels of n-3 polyunsaturated fatty acids (PUFAs) have been inversely related with risk of myocardial infarction (MI). Whether ratios of n-3 to n-6 PUFAs, reflecting both dietary intake of n-3 PUFAs and competing n-6 PUFAs, are better predictors of future MI than n-3 PUFA fractions is unclear. We aimed at investigating whether such ratios in adipose tissue better predict MI than n-3 PUFA fractions.
METHODS
Subcutaneous adipose tissue biopsies were obtained in a random sample (n = 3,500) of the Diet, Cancer and Health cohort (n = 57,053). Adipose tissue content of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), alpha-linolenic acid (ALA), arachidonic acid (AA) and linoleic acid was determined using gas chromatography. Fractions of selected n-3 PUFAs and n-3/n-6 PUFA ratios were correlated to the 15-year occurrence of MI in a case-cohort design.
RESULTS
A total of 2,406 participants experienced an MI during follow-up. Adipose tissue total marine n-3 PUFAs, EPA+DHA, EPA, EPA/AA, DHA/AA and (EPA + DPA + DHA)/AA were all inversely associated with risk of incident MI. Evaluating the predictive power (Harrel's C-index) of the selected metrics, fractions of marine n-3 PUFAs and ratios of EPA/AA, DHA/AA, (EPA + DHA)/AA and (EPA + DPA + DHA)/AA all refined risk prediction over age and sex alone. At multivariable analyses, however, the above ratios were the only metrics providing additional risk prediction. Differences in ratios were related to differences in food intake.
CONCLUSIONS
Both adipose tissue n-3 PUFAs fractions and ratios of n-3 PUFAs/AA were associated with a lower occurrence of MI, but ratios provided superior risk prediction. Dietary strategies affecting n-3/n-6 PUFA ratios should be further investigated for prediction of MI with dietary interventions at the population level and in intervention studies.
Topics: Humans; Fatty Acids, Omega-3; Fatty Acids; Eicosapentaenoic Acid; Fatty Acids, Omega-6; Arachidonic Acid; Myocardial Infarction; Adipose Tissue
PubMed: 37086938
DOI: 10.1016/j.ahj.2023.03.019 -
Immunity, Inflammation and Disease Nov 2023Immune dysfunction and oxidative stress caused by severe pneumonia can lead to multiple organ dysfunction and even death, causing a significant impact on health and the...
BACKGROUND
Immune dysfunction and oxidative stress caused by severe pneumonia can lead to multiple organ dysfunction and even death, causing a significant impact on health and the economy. Currently, great progress has been made in the diagnosis and treatment of this disease, but the mortality rate remains high (approximately 50%). Therefore, there is still potential for further exploration of the immune response mechanisms against severe pneumonia.
OBJECTIVE
This study analyzed the difference in serum metabolic profiles between patients with severe pneumonia and health individuals through metabolomics, aiming to uncover the correlation between the Tryptophan-Kynurenine pathway and the severity of severe pneumonia, as well as N-3/N-6 polyunsaturated fatty acids (PUFAs).
METHODS
In this study, 44 patients with severe pneumonia and 37 health controls were selected. According to the changes in the disease symptoms within the 7 days of admission, the patients were divided into aggravation (n = 22) and remission (n = 22) groups. Targeted metabolomics techniques were performed to quantify serum metabolites and analyze changes between groups.
RESULTS
Metabolomics analysis showed that serum kynurenine and kynurenine/tryptophan (K/T) were significantly increased and tryptophan was significantly decreased in patients with severe pneumonia; HETE and HEPE in lipids increased significantly, while eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), α-linolenic acid (linolenic acid, α-LNA), arachidonic acid (ARA), Dihomo-γ-linolenic acid (DGLA), and 13(s)-hydroperoxylinoleic acid (HPODE) decreased significantly. Additionally, the longitudinal comparison revealed that Linolenic acid, DPA, and Tryptophan increased significantly in the remission group, while and kynurenine and K/T decreased significantly. In the aggravation group, Kynurenine and K/T increased significantly, while ARA, 8(S)-hydroxyeicosatetraenoic acid (HETE), 11(S)-HETE, and Tryptophan decreased significantly. The correlation analysis matrix demonstrated that Tryptophan was positively correlated with DGLA, 12(S)-hydroxyeicosapentaenoic acid (HEPE), ARA, EPA, α-LNA, DHA, and DPA. Kynurenine was positively correlated with 8(S)-HETE and negatively correlated with DHA. Additionally, K/T was negatively correlated with DGLA, ARA, EPA, α-LNA, DHA, and DPA.
CONCLUSION
This study revealed that during severe pneumonia, the Tryptophan-Kynurenine pathway was activated and was positively correlated with the disease progression. On the other hand, the activation of the Tryptophan-Kynurenine pathway was negatively correlated with N-3/N-6 PUFAs.
Topics: Humans; Tryptophan; Kynurenine; Fatty Acids, Unsaturated; Fatty Acids, Omega-3; Inflammation; Arachidonic Acid; Pneumonia; Hydroxyeicosatetraenoic Acids; Linolenic Acids
PubMed: 38018595
DOI: 10.1002/iid3.1088 -
Journal of Oleo Science 2024In this study, the phospholipid species [i.e., phosphatidylethanolamine (PE), phosphatidylcholine (PC), and sphingomyelin (SM)] in human milk (HM) were compared...
In this study, the phospholipid species [i.e., phosphatidylethanolamine (PE), phosphatidylcholine (PC), and sphingomyelin (SM)] in human milk (HM) were compared according to their fatty acid (FA) composition. 34 HM samples were collected and classified into three groups (A < B < C) according to their fat content. Stearic acid (C18:0) was the main FA in PE, PC, and SM. The highest concentrations of arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosapentaenoic acid (DPA) were observed in PE, whereas docosahexaenoic acid (DHA) was predominant in SM. Although PC exhibited the highest total saturated FAs (SFAs) and PE contained the highest unsaturated FAs (UFAs), very long-chain SFAs and monounsaturated FAs (MUFAs) were preferentially distributed in SM. PC and SM had higher saturation compared to PE. Regarding the effect of the fat content of HM on the FA composition of the phospholipid species, a limited influence was observed on the composition of SFAs and MUFAs of PE, SM, and particularly PC. However, a more pronounced effect on the composition of polyunsaturated FAs (PUFAs) in phospholipids was observed, especially for linoleic acid (LA), α-linolenic acid (ALA), EPA, and DHA, indicating that the composition of FAs in the phospholipid species was probably affected by the maternal diet.
Topics: Humans; Fatty Acids; Phospholipids; Milk, Human; Linoleic Acid; Docosahexaenoic Acids; Eicosapentaenoic Acid; Phosphatidylcholines; Republic of Korea
PubMed: 38556280
DOI: 10.5650/jos.ess23185 -
Frontiers in Psychiatry 2023Abnormalities in membrane phospholipids are considered one of the pathophysiological backgrounds for schizophrenia. This study, explores the fatty acid composition of...
INTRODUCTION
Abnormalities in membrane phospholipids are considered one of the pathophysiological backgrounds for schizophrenia. This study, explores the fatty acid composition of erythrocyte membranes and its association with clinical characteristics in two groups: individuals with an at-risk mental state (ARMS) and patients experiencing their first-episode of schizophrenia (FES).
MATERIALS AND METHODS
This study measured erythrocyte membrane fatty acids in 72 antipsychotic-free individuals with ARMS, 18 antipsychotic-free patients with FES, and 39 healthy volunteers. Clinical symptoms and cognitive and social functions were assessed using the Positive and Negative Syndrome Scale (PANSS), Brief Assessment of Cognition in Schizophrenia (BACS), Schizophrenia Cognition Rating Scale (SCoRS), and Social and Occupational Functioning Assessment Scale (SOFAS).
RESULTS
Eicosapentaenoic and docosapentaenoic acid levels were lower in the ARMS and FES groups than in the healthy control group. In contrast, nervonic acid (NA) levels were markedly higher in the ARMS and FES groups than in the controls, while only the FES group showed higher levels of arachidonic acid. Oleic acid and NA levels were significantly associated with PANSS scores in both the FES and ARMS groups, particularly for the negative and general subscores. However, the patient groups had no significant associations between the fatty acid composition and the BACS, SCoRS, and SOFAS scores. Furthermore, the baseline fatty acid composition did not differ between the ARMS individuals who later developed psychosis ( = 6) and those who were followed for more than 2 years without developing psychosis onset ( = 30).
DISCUSSION
The findings suggest that abnormal fatty acid compositions may be shared in the early stages of schizophrenia and the clinical high-risk state for psychosis and may serve as vulnerability markers of psychopathology.
PubMed: 37564244
DOI: 10.3389/fpsyt.2023.1188452