Fatty Acid Metabolites Research Articles

Protein modification by short-chain fatty acid metabolites in sepsis: a comprehensive review.

Sepsis is a major life-threatening syndrome of organ dysfunction caused by a dysregulated host response due to infection. Dysregulated immunometabolism is fundamental to the onset of sepsis. Particularly, short-chain fatty acids (SCFAs) are gut microbes derived metabolites serving to drive the communication between gut microbes and the immune system, thereby exerting a profound influence on the pathophysiology of sepsis. Protein post-translational modifications (PTMs) have emerged as key players in shaping protein function, offering novel insights into the intricate connections between metabolism and phenotype regulation that characterize sepsis. Accumulating evidence from recent studies suggests that SCFAs can mediate various PTM-dependent mechanisms, modulating protein activity and influencing cellular signaling events in sepsis. This comprehensive review discusses the roles of SCFAs metabolism in sepsis associated inflammatory and immunosuppressive disorders while highlights recent advancements in SCFAs-mediated lysine acylation modifications, such as substrate supplement and enzyme regulation, which may provide new pharmacological targets for the treatment of sepsis.

High-fat ketogenic diets and ketone monoester supplements differentially affect substrate metabolism during aerobic exercise.

Chronically adhering to high-fat ketogenic diets or consuming ketone monoester supplements elicits ketosis. Resulting changes in substrate metabolism appear to be drastically different between ketogenic diets and ketone supplements. Consuming a ketogenic diet increases fatty acid oxidation with concomitant decreases in endogenous carbohydrate oxidation. Increased fat oxidation eventually results in an accumulation of circulating ketone bodies, which are metabolites of fatty acids that serve as an alternative source of fuel. Conversely, consuming ketone monoester supplements rapidly increases circulating ketone body concentrations that typically exceed those achieved by adhering to ketogenic diets. Rapid increases in ketone body concentrations with ketone monoester supplementation elicit a negative feedback inhibition that reduces fatty acid mobilization during aerobic exercise. Supplement-derived ketosis appears to have minimal impact on sparing of muscle glycogen or minimizing of carbohydrate oxidation during aerobic exercise. This review will discuss the substrate metabolic and associated aerobic performance responses to ketogenic diets and ketone supplements.

Serological short-chain fatty acid and trimethylamine N-oxide microbial metabolite imbalances in young adults with acute myocardial infarction

Acute myocardial infarction (AMI) is associated with systemic inflammatory processes and metabolic alterations. Microbial-derived metabolites, such as short-chain fatty acids and trimethylamine N-oxide (TMAO), have emerged in recent years as key players in the modulation of inflammation, with potential implications for cardiovascular diseases. We performed a prospective observational study that monitored the serological concentration of bacterial metabolites in 45 young patients (<55 years) without cardiovascular risk factors but with AMI, at hospital admission and at 3 months of follow-up, and compared them with a control group. TMAO and acetate levels were significantly higher in AMI, whereas butyrate and propionate were significantly lower. The acetate/propionate ratio showed the most discrimination between AMI and controls by receiver operating characteristic analysis (area under the curve 0.769, P < 0.0001). A multivariate logistic regression model revealed that this ratio was independently associated with AMI. Short-chain fatty acid concentrations, but not TMAO, exhibited significant correlations with inflammatory and coagulation parameters. Three months after the acute AMI event, all metabolite levels returned to those observed in healthy controls except butyrate. In conclusion, our study reveals disturbances of the serological concentration of microbiota-derived metabolites in AMI that are also related to inflammatory and coagulation parameters. These findings highlight an interesting field of study in the potential role of microbial metabolites from gut in cardiovascular disease.

Effects of ginseng on short-chain fatty acids and intestinal microbiota in rats with spleen-qi deficiency based on gas chromatography-mass spectrometry and 16s rRNA technology.

Spleen-qi deficiency syndrome, a common weakness syndrome in traditional Chinese medicine, results from insufficient spleen-qi levels. For centuries, ginseng has been relied upon as a traditional Chinese medicine to treat spleen-qi deficiency syndrome. Until now, the mechanism feature of ginseng in treating temper deficiency through intestinal bacteria and short-chain fatty acid (SCFA) metabolites has not been fully elucidated. This study established a rat model of spleen-qi deficiency via multi-factor compound modeling that involved fatigue injury and a controlled diet. The content of SCFAs between different treatment groups was determined by gas chromatography-mass spectrometry. And the 16s rRNA sequencing technology was applied to reveal the effects of ginseng on the intestinal microecological environment of the rats. It was found that the ginseng treatment group exhibited the most remarkable regulatory effect on propionic acid, surpassing all other administration groups. Ginseng increased the relative abundance of beneficial bacteria and decreased that of harmful bacteria at the genus level in rats with spleen-qi deficiency syndrome. And propionic acid is significantly positively correlated with Lactobacillus level and significantly negatively correlated with uncultured_bacterium_f_Muribaculaceae (p < 0.05). n-Butyric acid is negatively correlated with the Faecalibaculum level (p < 0.01). n-Valeric acid is significantly negatively correlated with the Romboutsia level (p < 0.01). The mechanism of ginseng treatment for spleen-qi deficiency is elucidated from the perspective of gut microbiota and its metabolite SCFAs. It provides a new way for further development and utilization of ginseng and a theoretical basis.

Strategy for characterization and quantification of fatty acids in plasma by parallel d0/d6-dansylhydrazine derivatization combined with UPLC–MS/MS

Fatty acids (FAs) play a vital physiological role in lipid metabolism, which is reported as potential diagnostic biomarker for various diseases. Thus, it is urgent to develop a credible method that can profile FA metabolism with a holistic view. Here, a targeted strategy to screen FAs was developed by parallel labeling with d0/d6-dansylhydrazine (d0/d6-DnsHz) and using ultra-high performance liquid chromatography coupled with high-resolution tandem mass spectrometry (UPLC–MS/MS) in data-dependent MS/MS (ddMS2) mode. The simple and mild derivatization procedure within 3 h allowed for a significant improvement in sensitivity. Additionally, the characteristic product ions introduced by the derivatization reagent assist to identify the unknown FA species. A quantitation method was established by multiple reaction monitoring (MRM) and the d6-DnsHz tagged standards for each analyte were used as internal standards to overcome the matrix effects. By applying the method to determine FA levels in plasma collected from the esophageal squamous cell carcinoma (ESCC) patients and healthy controls, 65 FA metabolites were characterized and six FAs were found to be altered by the invasion of tumors. The parallel derivatization strategy provides insights into the identification of unknown FAs and paves a new way for targeted metabolomics. Also, this novel method is a powerful tool for characterization and quantification of FAs in biological samples, which shows a great potential application in clinical diagnosis and investigation of disease mechanisms.

Association of Gut Flora and Short-Chain Fatty Acid Metabolite in Functional Constipation and Regulation of High-Fibre Diet on Them

Constipation is one of the most prevalent diseases in the world, and it has a significant impact on the quality of life of people. There are several critical factors associated with constipation, including short-chain fatty acid content and the composition of the gut microbiota. A disorder in any of these factors can cause an abnormal bowel movement and the symptoms of constipation. Diet regulates the gut microbiota and influences the immune system. Recent research suggests that high fibre foods promote the growth and stabilization of the intestinal nerves, as well as an increase in the number of useful bacteria found in the intestines. Fibre deficiency increases the risk of GI distress and contributes to poor gastrointestinal motility. Long-term treatment of constipation is dependent on developing a diet that provides sufficient fibre. A high fibre diet is probably not just essential to manage constipation, but also to lower the risk of developing other chronic illnesses associated with diet. In this paper, the relationship between high fibre diet and microbiota and short chain fatty acids in constipation patients is analyzed.

G protein-coupled receptor 55 activated by palmitoylethanolamide is associated with the development of nocturia associated with circadian rhythm disorders

AimsBladder function is regulated by clock genes and dysregulation of circadian bladder function can cause nocturia. The blood concentration of palmitoylethanolamide (PEA), a fatty acid metabolite, changes with circadian rhythm. Clock gene abnormalities demonstrate the highest PEA levels during the sleep phase. PEA is a GPR55 agonist that influences urination; therefore, increased PEA during the sleep phase may cause nocturia. Herein, we investigated the function of GPR55 to evaluate the relationship between GPR55 and nocturia that evoked higher PEA during the sleep phase in patients with circadian rhythm disorders. Main methodsMale C57BL/6 mice were used. GPR55 localization was evaluated by immunofluorescence staining, qRT-PCR, and western blotting. Variations in PEA-induced intracellular Ca2+ concentrations were measured in primary cultured mouse urothelial cells (UCs) using Ca2+ imaging. PEA-induced NGF and PGI2 release in UCs was measured by ELISA. The micturition reflex pathway after PEA administration was evaluated using immunofluorescence staining. Key findingsGPR55 was predominant in the UC layer. PEA induced release of Ca2+ from the endoplasmic reticulum into the UC cytoplasm. ELISA and immunofluorescence staining revealed that NGF and PGI2 were released from bladder UCs, stimulated the pontine micturition center in mice, and induced nocturia. SignificanceThe loss of regular circadian metabolizing rhythm in fatty acids causes higher blood PEA levels during the sleep phase. Binding of PEA to GPR55 in UC may activate the downstream processes of the micturition reflex, leading to nocturia. These findings suggest a new mechanism for nocturia and its potential as a therapeutic target.

A metabolomic investigation of serum perfluorooctane sulfonate and perfluorooctanoate

BackgroundExposures to perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA), environmentally persistent chemicals detectable in the blood of most Americans, have been associated with several health outcomes. To offer insight into their possible biologic effects, we evaluated the metabolomic correlates of circulating PFOS and PFOA among 3,647 participants in eight nested case-control serum metabolomic profiling studies from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. MethodsMetabolomic profiling was conducted by Metabolon Inc., using ultra high-performance liquid chromatography/tandem accurate mass spectrometry. We conducted study-specific multivariable linear regression analyses estimating the associations of metabolite levels with levels of PFOS or PFOA. For metabolites measured in at least 3 of 8 nested case-control studies, random effects meta-analysis was used to summarize study-specific results (1,038 metabolites in PFOS analyses and 1,100 in PFOA analyses). ResultsThe meta-analysis identified 51 and 38 metabolites associated with PFOS and PFOA, respectively, at a Bonferroni-corrected significance level (4.8x10-5 and 4.6x10-5, respectively). For both PFOS and PFOA, the most common types of associated metabolites were lipids (sphingolipids, fatty acid metabolites) and xenobiotics (xanthine metabolites, chemicals). Positive associations were commonly observed with lipid metabolites sphingomyelin (d18:1/18:0) (P = 2.0x10-10 and 2.0x10-8, respectively), 3-carboxy-4-methyl-5-pentyl-2-furanpropionate (P = 2.7x10-15, 1.1x10-17), and lignoceroylcarnitine (C24) (P = 2.6x10-8, 6.2x10-6). The strongest positive associations were observed for chemicals 3,5-dichloro-2,6-dihydroxybenzoic acid (P = 3.0x10-112 and 6.8x10-13, respectively) and 3-bromo-5-chloro-2,6-dihydroxybenzoic acid (P = 1.6x10-14, 2.3x10-6). Other metabolites positively associated with PFOS included D-glucose (carbohydrate), carotene diol (vitamin A metabolism), and L-alpha-aminobutyric acid (glutathione metabolism), while uric acid (purine metabolite) was positively associated with PFOA. PFOS associations were consistent even after adjusting for PFOA as a covariate, while PFOA associations were greatly attenuated with PFOS adjustment. ConclusionsIn this large metabolomic study, we observed robust positive associations with PFOS for several molecules. Further investigation of these metabolites may offer insight into PFOS-related biologic effects.

Bacteroides Fragilis in the gut microbiomes of Alzheimer’s disease activates microglia and triggers pathogenesis in neuronal C/EBPβ transgenic mice

Gut dysbiosis contributes to Alzheimer’s disease (AD) pathogenesis, and Bacteroides strains are selectively elevated in AD gut microbiota. However, it remains unknown which Bacteroides species and how their metabolites trigger AD pathologies. Here we show that Bacteroides fragilis and their metabolites 12-hydroxy-heptadecatrienoic acid (12-HHTrE) and Prostaglandin E2 (PGE2) activate microglia and induce AD pathogenesis in neuronal C/EBPβ transgenic mice. Recolonization of antibiotics cocktail-pretreated Thy1-C/EBPβ transgenic mice with AD patient fecal samples elicits AD pathologies, associated with C/EBPβ/Asparaginyl endopeptidase (AEP) pathway upregulation, microglia activation, and cognitive disorders compared to mice receiving healthy donors’ fecal microbiota transplantation (FMT). Microbial 16S rRNA sequencing analysis shows higher abundance of proinflammatory Bacteroides fragilis in AD-FMT mice. Active components characterization from the sera and brains of the transplanted mice revealed that both 12-HHTrE and PGE2 activate primary microglia, fitting with poly-unsaturated fatty acid (PUFA) metabolites enrichment identified by metabolomics. Strikingly, recolonization with live but not dead Bacteroides fragilis elicited AD pathologies in Thy1-C/EBPβ transgenic mice, so did 12-HHTrE or PGE2 treatment alone. Collectively, our findings support a causal role for Bacteroides fragilis and the PUFA metabolites in activating microglia and inducing AD pathologies in Thy1- C/EBPβ transgenic mice.

Impact of the lipase inhibitor orlistat on the human gut microbiota

Orlistat, an anti-obesity agent, inhibits the metabolism and absorption of dietary fat by inactivating pancreatic lipase in the gut. The effect of orlistat on the gut microbiota of Japanese individuals with obesity is unknown. This study aimed to explore the effects of orlistat on the gut microbiota and fatty acid metabolism of Japanese individuals with obesity. Fourteen subjects with visceral fat obesity (waist circumference ≥85 cm) took orlistat orally at a dose of 60 mg, 3 times a day for 8 weeks. Body weight; waist circumference; visceral fat area; levels of short-chain fatty acids, gut microbiota, fatty acid metabolites in the feces, and gastrointestinal hormones; and adverse events were evaluated. Body weight, waist circumference, and blood leptin concentrations were significantly lower after orlistat treatment (mean ± standard deviation, 77.8 ± 9.1 kg; 91.9 ± 8.7 cm; and 4546 ± 3211 pg/mL, respectively) compared with before treatment (79.4 ± 9.0 kg; 94.4 ± 8.0 cm; and 5881 ± 3526 pg/mL, respectively). Significant increases in fecal levels of fatty acid metabolites (10-hydroxy-cis-12-octadecenoic acid, 10-oxo-cis-12-octadecenoic acid, and 10-oxo-trans-11-octadecenoic acid) were detected. Meanwhile, no significant changes were found in abdominal computed tomography parameters, blood marker levels, or short-chain fatty acid levels in the feces. Gut microbiota analysis revealed that some study subjects had decreased abundance of Firmicutes, increased abundance of Bacteroidetes, and increased α-diversity indices (Chao1 and ACE) after 8 weeks of treatment. The levels of Lactobacillus genus and Lactobacillus gasseri were significantly higher after 8 weeks of treatment. None of the subjects discontinued treatment or experienced severe adverse events. This study suggested that orlistat might alter gut microbiota composition and affect the body through fatty acid metabolites produced by the modified gut bacteria.

Effect of cardiopulmonary bypass on plasma and erythrocytes oxylipins

BackgroundOxylipins, the oxidative metabolites of polyunsaturated fatty acids (PUFAs), serve as key mediators of oxidative stress, inflammatory responses, and vasoactive reactions in vivo. Our previous work has established that hemodialysis affects both long chain fatty acids (LCFAs) and oxylipins in plasma and erythrocytes to varying degrees, which may be responsible for excess cardiovascular complications in end-stage renal disease. In this study, we aimed to determine changes in blood oxylipins during cardiopulmonary bypass (CPB) in patients undergoing cardiac surgery to identify novel biomarkers and potential metabolites of CPB-related complications. We tested the hypothesis that CPB would differentially affect plasma oxylipins and erythrocytes oxylipins.MethodsWe conducted a prospective observational study of 12 patients undergoing elective cardiac surgery with expected CPB procedure. We collected venous and arterial blood samples before CPB, 15 and 45 min after the start of CPB, and 60 min after the end of CPB, respectively. Oxylipins profiling in plasma and erythrocytes was achieved using targeted HPLC‐MS mass spectrometry.ResultsOur results revealed that most venous plasma diols and hydroxy- oxylipins decreased after CPB initiation, with a continuous decline until the termination of CPB. Nevertheless, no statistically significant alterations were detected in erythrocytes oxylipins at all time points.ConclusionsCPB decreases numerous diols and hydroxy oxylipins in blood plasma, whereas no changes in erythrocytes oxylipins are observed during this procedure in patients undergoing cardiac surgery. As lipid mediators primarily responsive to CPB, plasma diols and hydroxy oxylipins may serve as potential key biomarkers for CPB-related complications.

Inulin Attenuates Blood-Brain Barrier Permeability and Alleviates Behavioral Disorders by Modulating the TLR4/MyD88/NF-κB Pathway in Mice with Chronic Stress.

Depression and vulnerability to chronic stress are associated with inflammatory responses and the loss of blood-brain barrier (BBB) integrity. Dietary fiber and its short-chain fatty acid (SCFAs) metabolites have been reported to affect neuropsychiatric disorders. Here, a 9-week treatment course of inulin (0.037 g of inulin/kcal) exhibited in chronic unpredictable mild stress (CUMS) mice led to antidepressant and anxiolytic effects, as well as improved neurogenesis and synaptic plasticity by enhancing CREB/BDNF signaling. Importantly, inulin inhibited CUMS-induced decreased BBB permeability, reduced lipopolysaccharide (LPS) brain penetration, and modulated TLR4/MyD88/NF-κB signaling to alleviate neuroinflammatory responses. Furthermore, inulin protected the gut barrier integrity and led to the increased formation of SCFAs. Enhanced SCFAs formation was strongly positively correlated with behavioral improvements, BBB integrity, and neuroinflammatory responses. We speculate that dietary fiber may be a promising nutritional intervention to reverse the effects of chronic stress by regulating metabolites and protecting the BBB integrity.

Short-communication: Study of fatty acid metabolites in microbial conjugated fatty acids-enrichment of milk and discovery of additional undescribed conjugated linolenic acid isomers

Microbially enriched food in conjugated linoleic (CLA) and conjugated linolenic (CLNA) acids is intensively studied nowadays. The conversion of linoleic (LA) and α-linolenic acids (α-LNA) into these compounds may involve different fatty acid (FA) intermediates. This research aimed to investigate potential FA byproducts in milk during microbial CLA/CLNA-enrichment using Bifidobacterium breve DSM 20091. Milk fermented with pure α-LNA showed a decrease in free myristic acid, while pure LA led to an increase in free stearic acid. No additional FA compounds were found alongside CLA/CLNA isomers. The strain produced several CLA isomers from LA, but only when administered alone. Nonetheless, when α-LNA was assayed, additional CLNA isomers, never reported before for bifidobacteria, were observed. In conclusion, except for stearic acid in the presence of LA, no side-FA metabolites were released during milk microbial CLA/CLNA-enrichment. Results suggest either CLA/CLNA production occurs in one single-step or intermediates biotransformation is very fast.

The link between obesity and insulin resistance among children: Effects of key metabolites.

Childhood obesity became a severe public health challenge, and insulin resistance (IR) was one of the common complications. Both obesity and IR were considered as the basis of metabolic disorders. However, it is unclear which common key metabolites are associated with childhood obesity and IR. The children were divided into normal weight and overweight/obese groups. Fasting blood glucose and fasting insulin were measured, and homeostasis model assessment of insulin resistance was calculated. Liquid chromatography-tandem mass spectrometry was applied for metabonomic analysis. Multiple linear regression analysis and correlation analysis explored the relationships between obesity, IR, and metabolites. Random forests were used to rank the importance of differential metabolites, and relative operating characteristic curves were used for prediction. A total of 88 normal-weight children and 171 obese/overweight children participated in the study. There was a significant difference between the two groups in 30 metabolites. Childhood obesity was significantly associated with 10 amino acid metabolites and 20 fatty acid metabolites. There were 12 metabolites significantly correlated with IR. The ranking of metabolites in random forest showed that glutamine, tyrosine, and alanine were important in amino acids, and pyruvic-ox-2, ethylmalonic-2, and phenyllactic-2 were important in fatty acids. The area under the curve of body mass index standard deviation score (BMI-SDS) combined with key amino acid metabolites and fatty acid metabolites for predicting IR was 80.0% and 76.6%, respectively. There are common key metabolites related to IR and obese children, and these key metabolites combined with BMI-SDS could effectively predict the risk of IR.

Intestinal acetic acid regulates the synthesis of sex pheromones in captive giant pandas.

As a typical solitary animal, adult giant pandas rely on chemical signals (sex pheromones) to transmit reproductive information during oestrous. Although researchers have confirmed that the gut microbiota is related to the emission and reception of sex pheromones, there is no clear correlation between the gut microbes and the synthesis of sex pheromone of giant pandas, that is, which gut microbes and microbial metabolites are participate in the synthesis of giant panda's sex pheromone. As a mirror of gut microbiota, fecal microbiota can reflect the composition of gut microbiota and its interaction with host to some extent. The purpose of this study is to explore how the gut microbes affect the synthesis of sex pheromones in captive giant pandas by combining analysis of the fecal microbiome and metabolomics. The results of correlation and microbial function analysis show that intestinal microorganisms such as Veillonellaceae and Lactobacillilaceae are associated with the synthesis of short chain fatty acid (acetic acid) and volatile ester metabolites, such as 1-butanol, 3-methyl, acetate, acetic acid, hexyl ester and 3-hexen-1-ol, acetate, (Z). In summary, based on this study, we believe that volatile metabolites such as fecal acetate participate in the process of mate preference of captive giant pandas and affect their expression of natural mating behavior. The possible mechanism is that the gut microbes can promote the synthesis of key chemical signaling substances in perianal glands through mediated intermediate fecal metabolites, thus affecting the normal information exchange between giant pandas individuals. The results of this study have greatly enriched our understanding of gut microbes regulating the synthesis of sex pheromones in giant pandas.

Characterization of bioactive fatty acid metabolites produced by the halophilic Idiomarina sp. OM679414.1 for their antimicrobial and anticancer activity

Characterization of bioactive fatty acid metabolites produced by the halophilic Idiomarina sp. OM679414.1 for their antimicrobial and anticancer activity

Microbial short-chain fatty acids regulate drug seeking and transcriptional control in a model of cocaine seeking.

Cocaine use disorder represents a public health crisis with no FDA-approved medications for its treatment. A growing body of research has detailed the important connections between the brain and the resident population of bacteria in the gut, the gut microbiome, in psychiatric disease models. Acute depletion of gut bacteria results in enhanced reward in a mouse cocaine place preference model, and repletion of bacterially-derived short-chain fatty acid (SCFA) metabolites reverses this effect. However, the role of the gut microbiome and its metabolites in modulating cocaine-seeking behavior after prolonged abstinence is unknown. Given that relapse prevention is the most clinically challenging issue in treating substance use disorders, studies examining the effects of microbiome manipulations in relapse-relevant models are critical. Here, male Sprague-Dawley rats received either untreated water or antibiotics to deplete the gut microbiome and its metabolites. Rats were trained to self-administer cocaine and subjected to either within-session threshold testing to evaluate motivation for cocaine or 21 days of abstinence followed by a cue-induced cocaine-seeking task to model relapse behavior. Microbiome depletion did not affect cocaine acquisition on an fixed-ratio 1 schedule. However, microbiome-depleted rats exhibited significantly enhanced motivation for low dose cocaine on a within-session threshold task. Similarly, microbiome depletion increased cue-induced cocaine-seeking following prolonged abstinenceand altered transcriptional regulation in the nucleus accumbens. In the absence of a normal microbiome, repletion of bacterially-derived SCFA metabolites reversed the behavioral and transcriptional changes associated with microbiome depletion. These findings suggest that gut bacteria, via their metabolites, are key regulators of drug-seeking behaviors, positioning the microbiome as a potential translational research target.

Furan fatty acid metabolite CMPF is associated with lower risk of type 2 diabetes, but not chronic kidney disease: a longitudinal population-based cohort study

BackgroundFuran fatty acid metabolite 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) is a strong biomarker of fish and n-3 polyunsaturated fatty acid (PUFA) intake. The relationship of CMPF with human health has been controversial, especially for type 2 diabetes and chronic kidney disease. ObjectiveWe performed a prospective cohort study to examine the association of serum CMPF with incident type 2 diabetes and chronic kidney disease. MethodsIn the Guangzhou Nutrition and Health Study, during a median follow-up of 8.8 y, we used a multivariable-adjusted Poisson regression model to investigate the association of baseline serum CMPF with the incidence of type 2 diabetes (1470 participants and 170 incident cases) and chronic kidney disease (1436 participants and 112 incident cases). We also examined the association of serial measures of serum CMPF with glycemic and renal function biomarkers. Mediation analysis was also performed to examine the contribution of CMPF in the association between marine n-3 PUFAs and risk of type 2 diabetes or chronic kidney disease. ResultsEach standard deviation increase in baseline serum CMPF was associated with an 18% lower risk of type 2 diabetes (relative risk: 0.82, 95% confidence interval [CI]: 0.68, 0.99) but was not associated with chronic kidney disease (relative risk: 0.95; 95% CI: 0.77-1.16). Correlation analyses of CMPF with glycemic and renal function biomarkers showed similar results. Mediation analysis suggested that serum CMPF contributed to the inverse association between erythrocyte marine n-3 PUFAs and incident type 2 diabetes (proportion mediated 37%, P-mediation = 0.022). ConclusionsOur findings suggest that serum CMPF was associated with a lower risk of type 2 diabetes but not chronic kidney disease. This study also suggests that CMPF may be a functional metabolite underlying the protective relationship between marine n-3 PUFA intake and type 2 diabetes.

Comprehensive Changes in Nutrient Constituents and Antioxidant Activity during Food Processing of Isoflavone-Enriched Soybean Leaf by Mycelia of Tricholoma matsutake

We studied the changes induced in pH, acidity, brix, reducing sugar, soluble protein, nutritional components, primary metabolites, and antioxidant activities of isoflavone-enriched soybean leaf during the different stages involved in Tricholoma matsutake mycelia fermenting. We found that total fatty acid contents increased sequentially in dried soybean leaf, sterilized soybean leaf, and fermented soybean leaf (413.8, 420.3, and 909.4 mg/100 g, respectively). Particularly, linoleic acid content was 5-fold higher in the fermented soybean leaf than in the previous stages. The total free amino acid contents were decreased with progressing processing stages (2389.71, 1860.90, and 1434.25 mg/100 g). However, glutamic acid and lysine contents were highest in fermented soybean leaves. Total mineral contents increased with progressing processing stages (40.30, 41.72, and 55.32 mg/100 g). Water-soluble vitamins, riboflavin, and niacin were about 26-fold and 2.6-fold higher, respectively, in fermented soybean leaf. Comprehensive data analysis of primary metabolites detected changes in a total of 28 metabolites, including, amino acids, organic acids, carbohydrates, and fatty acid metabolites. Antioxidant activities were measured by 2,2-diphenyl-1-picrylhydrazyl, 2,2-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid), and hydroxyl radical scavenging activities and ferric-reducing antioxidant power. Overall, the antioxidant activities increased with progressing processing stages. Thus, we show that T. matsutake mycelia fermented isoflavone-enriched soybean leaf products have excellent nutritional value.

Ancestry-driven metabolite variation provides insights into disease states in admixed populations

BackgroundMetabolic pathways are related to physiological functions and disease states and are influenced by genetic variation and environmental factors. Hispanics/Latino individuals have ancestry-derived genomic regions (local ancestry) from their recent admixture that have been less characterized for associations with metabolite abundance and disease risk.MethodsWe performed admixture mapping of 640 circulating metabolites in 3887 Hispanic/Latino individuals from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Metabolites were quantified in fasting serum through non-targeted mass spectrometry (MS) analysis using ultra-performance liquid chromatography-MS/MS. Replication was performed in 1856 nonoverlapping HCHS/SOL participants with metabolomic data.ResultsBy leveraging local ancestry, this study identified significant ancestry-enriched associations for 78 circulating metabolites at 484 independent regions, including 116 novel metabolite-genomic region associations that replicated in an independent sample. Among the main findings, we identified Native American enriched genomic regions at chromosomes 11 and 15, mapping to FADS1/FADS2 and LIPC, respectively, associated with reduced long-chain polyunsaturated fatty acid metabolites implicated in metabolic and inflammatory pathways. An African-derived genomic region at chromosome 2 was associated with N-acetylated amino acid metabolites. This region, mapped to ALMS1, is associated with chronic kidney disease, a disease that disproportionately burdens individuals of African descent.ConclusionsOur findings provide important insights into differences in metabolite quantities related to ancestry in admixed populations including metabolites related to regulation of lipid polyunsaturated fatty acids and N-acetylated amino acids, which may have implications for common diseases in populations.