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Nutrition Research (New York, N.Y.) Nov 2023Diabetic foot (DF) is one of the serious chronic complications of diabetes. Accurate prediction of the risk of DF may take timely intervention measures to prevent its...
Diabetic foot (DF) is one of the serious chronic complications of diabetes. Accurate prediction of the risk of DF may take timely intervention measures to prevent its occurrence. The understanding of metabolomic changes in the progression of diabetes to DF may reveal new targets for interventions. We hypothesized that changes in metabolic pathways during DF would lead to changes in the metabolic profile, which could be predictive signature specific to it. In the present study, 43 participants with type 2 diabetes mellitus (T2DM), 32 T2DM participants with DF (T2DM-F), and 36 healthy subjects were enrolled and their serum samples were used for targeted and nonpolar metabolic analysis with liquid chromatography-tandem mass spectrometry. Differential metabolites related to T2DM-F were discovered in metabolomic analysis. Lasso machine learning regression model, random forest algorithm, causal mediation analysis, disease risk assessment, and clinical decision model were carried out. T2DM and T2DM-F groups could be distinguished with the healthy control group. The differential metabolites were all enriched in alpha-linolenic acid and linoleic acid metabolic pathways including arachidonic acid, docosapentaenoic-acid 22N-6, and docosahexaenoic-acid, which were significantly lower in the T2DM and T2DM-F groups compared with the healthy control group. The differential metabolites in T2DM-F vs T2DM groups were enriched to branched-chain amino acid (BCAA) catabolic pathways involving in methylmalonic acid, succinic acid, 3-methyl-2-oxovaleric acid, and ketoleucine, which were the BCAA catabolic intermediates and significantly lower in the T2DM-F compared with the T2DM group except for succinic acid. We reveal a new set of predictive signatures and associate the lower BCAA catabolic intermediates with the progression from T2DM to T2DM-F.
Topics: Humans; Diabetes Mellitus, Type 2; Diabetic Foot; Succinic Acid; Amino Acids, Branched-Chain; Metabolomics
PubMed: 37716292
DOI: 10.1016/j.nutres.2023.08.009 -
Nutrients Apr 2024Colorectal cancer (CRC), a major global health concern, may be influenced by dietary protein digestibility impacting gut microbiota and metabolites, which is crucial for...
Colorectal cancer (CRC), a major global health concern, may be influenced by dietary protein digestibility impacting gut microbiota and metabolites, which is crucial for cancer therapy effectiveness. This study explored the effects of a casein protein diet (CTL) versus a free amino acid (FAA)-based diet on CRC progression, gut microbiota, and metabolites using carcinogen-induced (AOM/DSS) and spontaneous genetically induced ( mice) CRC mouse models. Comprehensive approaches including 16s rRNA gene sequencing, transcriptomics, metabolomics, and immunohistochemistry were utilized. We found that the FAA significantly attenuated CRC progression, evidenced by reduced colonic shortening and histopathological alterations compared to the CTL diet. Notably, the FAA enriched beneficial gut bacteria like and and reversed CRC-associated dysbiosis. Metabolomic analysis highlighted an increase in ornithine cycle metabolites and specific fatty acids, such as Docosapentaenoic acid (DPA), in FAA-fed mice. Transcriptomic analysis revealed that FAA up-regulated Egl-9 family hypoxia inducible factor 3 (Egln 3) and downregulated several cancer-associated pathways including Hippo, mTOR, and Wnt signaling. Additionally, DPA was found to significantly induce EGLN 3 expression in CRC cell lines. These results suggest that FAA modulate gut microbial composition, enhance protective metabolites, improve gut barrier functions, and inhibit carcinogenic pathways.
Topics: Animals; Mice; Gastrointestinal Microbiome; RNA, Ribosomal, 16S; Carcinogenesis; Cell Transformation, Neoplastic; Carcinogens; Amino Acids; Colorectal Neoplasms
PubMed: 38613073
DOI: 10.3390/nu16071040 -
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 -
The Ocular Surface Jul 2024Polyunsaturated fatty acids (PUFA) are a source of bioactive lipids regulating inflammation and its resolution.
PURPOSE
Polyunsaturated fatty acids (PUFA) are a source of bioactive lipids regulating inflammation and its resolution.
METHODS
Changes in PUFA metabolism were compared between lacrimal glands (LGs) from young and aged C57BL/6 J mice using a targeted lipidomics assay, as was the gene expression of enzymes involved in the metabolism of these lipids.
RESULTS
Global reduction in PUFAs and their metabolites was observed in aged LGs compared to young controls, averaging between 25 and 66 % across all analytes. ꞷ-6 arachidonic acid (AA) metabolites were all reduced in aged LGs, where the changes in prostaglandin E2 (PGE2) and lipoxin A4 (LXA4) were statistically significant. Several other 5-lipoxygenase (5-LOX) mediated metabolites were significantly reduced in the aged LGs, including D-series resolvins (e.g., RvD4, RvD5, and RvD6). Along with the RvDs, several ꞷ-3 docosahexaenoic acid (DHA) metabolites such as 14-HDHA, neuroprotectin D1 (NPD1), Maresin 2 (MaR2), and MaR 1 metabolite (22-COOH-MaR1) were significantly reduced in aged LGs. Similarly, ꞷ-3 eicosapentaenoic acid (EPA) and its metabolites were significantly reduced in aged LGs, where the most significantly reduced was 18-HEPE. Using metabolite ratios (product:precursor) for specific metabolic conversions as surrogate enzymatic measures, reduced 12-LOX activity was identified in aged LGs.
CONCLUSION
In this study, global reduction of PUFAs and their metabolites was found in the LGs of aged female C57BL/6 J compared to young controls. A consistent reduction was observed across all detected lipid analytes except for ꞷ-3 docosapentaenoic acid (DPA) and its special pro-resolving mediator (SPM) metabolites in aged mice, suggesting an increased risk for LG inflammation.
Topics: Animals; Mice, Inbred C57BL; Mice; Fatty Acids, Unsaturated; Aging; Lacrimal Apparatus; Lipid Metabolism; Female; Lipidomics
PubMed: 38705236
DOI: 10.1016/j.jtos.2024.04.008 -
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 -
The British Journal of Nutrition Oct 2023Circulating -3 PUFA, which integrate endogenous and exogenous -3 PUFA, can be better used to investigate the relationship between -3 PUFA and disease. However, studies...
Circulating -3 PUFA, which integrate endogenous and exogenous -3 PUFA, can be better used to investigate the relationship between -3 PUFA and disease. However, studies examining the associations between circulating -3 PUFA and colorectal cancer (CRC) risk were limited, and the results remained inconclusive. This case–control study aimed to examine the association between serum -3 PUFA and CRC risk in Chinese population. A total of 680 CRC cases and 680 sex- and age-matched (5-year interval) controls were included. Fatty acids were assayed by GC. OR and 95 % CI were calculated using multivariable logistic regression after adjustment for potential confounders. Higher level of serum α-linolenic acid (ALA), docosapentaenoic acid (DPA), DHA, long-chain -3 PUFA and total -3 PUFA were associated with lower odds of CRC. The adjusted OR and 95 % CI were 0·34 (0·24, 0·49, < 0·001) for ALA, 0·57 (0·40, 0·80, < 0·001) for DPA, 0·48 (0·34, 0·68, < 0·001) for DHA, 0·39 (0·27, 0·56, < 0·001) for long-chain -3 PUFA and 0·31 (0·22, 0·45, < 0·001) for total -3 PUFA comparing the highest with the lowest quartile. However, there was no statistically significant association between EPA and odds of CRC. Analysis stratified by sex showed that ALA, DHA, long-chain -3 PUFA and total -3 PUFA were inversely associated with odds of CRC in both sexes. This study indicated that serum ALA, DPA, DHA, long-chain -3 PUFA and total -3 PUFA were inversely associated with odds of having CRC in Chinese population.
Topics: Female; Humans; Male; Case-Control Studies; Colorectal Neoplasms; East Asian People; Fatty Acids; Fatty Acids, Omega-3
PubMed: 36746393
DOI: 10.1017/S0007114523000351 -
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 -
Biotechnology Letters Jun 2024Currently, there is lack of a consistent and highly enriched source for docosapentaenoic acid (n-3 DPA, C22:5), and this work report the isolation of microorganism that...
OBJECTIVE
Currently, there is lack of a consistent and highly enriched source for docosapentaenoic acid (n-3 DPA, C22:5), and this work report the isolation of microorganism that naturally produces n-3 DPA.
RESULTS
In this work, we screened microorganisms in our culture collections with the goal to isolate a strain with high levels of n-3 DPA. We isolated a strain of Sphaeroforma arctica that produces up to 11% n-3 DPA in total fatty acid and has a high n-3 DPA to DHA/EPA ratio. The cell growth of the isolated strain was characterized using microscopy imaging and flow cytometer technologies to confirm the coenocytic pattern of cell divisions previously described in S. arctica. Our novel isolate of S. arctica grew more robustly and produced significantly more n-3 DPA compared to previously isolated and described strains indicating the uniqueness of the discovered strain.
CONCLUSION
Overall, this work reports a first isolate n-3 DPA producing microorganism and establishes the foundation for future strain improvement and elucidation of the physiological function of this LC-PUFA for human nutrition and health.
Topics: Fatty Acids, Unsaturated; Stramenopiles
PubMed: 38493279
DOI: 10.1007/s10529-024-03472-5 -
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