Altered Fatty Acid Research Articles

Short-Term Metformin Protects Against Glucocorticoid-Induced Toxicity in Healthy Subjects: A Randomized, Double-Blind, Placebo-Controlled Trial.

Glucocorticoids (GCs) are potent anti-inflammatory drugs, but strategies to prevent side effects are lacking. We investigated whether metformin could prevent GC-related toxicity and explored the underlying mechanisms. This single-center, randomized, placebo-controlled, double-blind, crossover trial compared metformin with placebo during high-dose GC treatment in 18 lean, healthy, male study participants. The trial was conducted at the University Hospital Basel, Switzerland. Participants received prednisone 30 mg/d in combination with metformin or placebo for two 7-day periods (1:1 randomization). The primary outcome, change in insulin sensitivity, was assessed using a two-sided paired t test. Before and after each study period, we conducted a mixed-meal tolerance test, blood metabolomics, and RNA sequencing of subcutaneous adipose tissue biopsy specimens. Metformin improved insulin sensitivity as assessed by the Matsuda index (n = 17; mean change: -2.73 ± 3.55 SD for placebo, 2.21 ± 3.95 for metformin; mean difference of change -4.94 [95% CI, -7.24, -2.65)]; P < 0.001). Metabolomic and transcriptomic analyses revealed that metformin altered fatty acid flux in the blood and downregulated genes involved in fatty acid synthesis in adipose tissue. Metformin reduced markers of protein breakdown and bone resorption. Furthermore, metformin downregulated genes responsible for AMPK inhibition and affected GLP1 and bile acid metabolism. Metformin prevents GC-induced insulin resistance and reduces markers of dyslipidemia, myopathy, and, possibly, bone resorption through AMPK-dependent and -independent pathways.

Microbiota and immune dynamics in rheumatoid arthritis: Mechanisms and therapeutic potential.

Rheumatoid arthritis (RA) is a complex autoimmune disease with growing evidence implicating the microbiota as a critical contributor to its pathogenesis. This review explores the multifaceted roles of microbial dysbiosis in RA, emphasizing its impact on immune cell modulation, autoantibody production, gut barrier integrity, and joint inflammation. Animal models reveal how genetic predisposition and environmental factors interact with specific microbial taxa to influence disease susceptibility. Dysbiosis-driven metabolic disruptions, including alterations in short-chain fatty acids and bile acids, further exacerbate immune dysregulation and systemic inflammation. Emerging therapeutic strategies-probiotics, microbial metabolites, fecal microbiota transplantation, and antibiotics-offer innovative avenues for restoring microbial balance and mitigating disease progression. By integrating microbiota-targeted approaches with existing treatments, this review highlights the potential to revolutionize RA management through precision medicine and underscores the need for further research to harness the microbiota's therapeutic potential.

Impact of psychostimulants on microbiota and short-chain fatty acids alterations in children with attention-deficit/hyperactivity disorder

Attention-deficit/hyperactivity disorder (ADHD), a common neurodevelopmental disorder in children, is associated with alterations in gut microbiota and short-chain fatty acids (SCFAs), which are metabolites influencing the gut-brain axis. Evidence suggests that psychostimulant medications, widely used to manage ADHD symptoms, may also impact gut microbiota composition and SCFA levels. This study explores these potential effects by examining gut microbiota profiles and SCFA concentrations in unmedicated and medicated children with ADHD, compared to healthy controls. Fecal samples from 30 children aged 6–12 years (10 unmedicated ADHD, 10 medicated ADHD, and 10 healthy controls) were analyzed using 16 S rRNA sequencing and targeted metabolomics. Unmedicated ADHD children show distinct gut microbiota profiles, with lower level of Tyzzerella, Prevotellaceae, and Coriobacteriaceae, compared to controls. Notably, propionic acid levels were negatively associated with ADHD symptom severity, suggesting a potential biomarker role. Medicated ADHD children showed lower gut microbial diversity, unique taxa, and lower SCFA levels, compared to unmedicated children with ADHD. These findings suggest that gut microbiota and SCFAs may be linked to ADHD symptomatology, underscoring the importance of gut-brain interactions in ADHD. This study highlights the potential of gut health monitoring as part of future ADHD management strategies.

Phase I trial comparing bile acid and short-chain fatty acid alterations in stool collected from human subjects treated with omadacycline or vancomycin.

The purpose of this study was to assess bile acid and SCFA changes in stool samples obtained from healthy volunteers given omadacycline or vancomycin. Stool samples were collected daily from 16 healthy volunteers given a 10-day oral course of omadacycline or vancomycin. Vancomycin caused a larger change in the primary bile acids and SCFA concentrations compared with omadacycline. The metabolic findings help further our understanding of the mechanistic basis for the lower-risk properties of omadacycline causing CDI and warrant phase 2 investigations using omadacycline as a CDI antibiotic. This study is registered with ClinicalTrials.gov as NCT06030219.

A machine learning model accurately identifies glycogen storage disease Ia patients based on plasma acylcarnitine profiles

BackgroundGlycogen storage disease (GSD) Ia is an ultra-rare inherited disorder of carbohydrate metabolism. Patients often present in the first months of life with fasting hypoketotic hypoglycemia and hepatomegaly. The diagnosis of GSD Ia relies on a combination of different biomarkers, mostly routine clinical chemical markers and subsequent genetic confirmation. However, a specific and reliable biomarker is lacking. As GSD Ia patients demonstrate altered lipid metabolism and mitochondrial fatty acid oxidation, we built a machine learning model to identify GSD Ia patients based on plasma acylcarnitine profiles.MethodsWe collected plasma acylcarnitine profiles from 3958 patients, of whom 31 have GSD Ia. Synthetic samples were generated to address the problem of class imbalance in the dataset. We built several machine learning models based on gradient-boosted trees. Our approach included hyperparameter tuning and feature selection and generalization was checked using both nested cross-validation and a held-out test set.ResultsThe binary classifier was able to correctly identify 5/6 GSD Ia patients in a held-out test set without generating significant amounts of false positive results. The best model showed excellent performance with a mean received operator curve (ROC) AUC of 0.955 and precision-recall (PR) curve AUC of 0.674 in nested CV.ConclusionsThis study demonstrates an innovative approach to applying machine learning to ultra-rare diseases by accurately identifying GSD Ia patients based on plasma free carnitine and acylcarnitine concentrations, leveraging subtle acylcarnitine abnormalities. Acylcarnitine features that were strong predictors for GSD Ia include C16-carnitine, C14OH-carnitine, total carnitine and acetylcarnitine. The model demonstrated high sensitivity and specificity, with selected parameters that were not only robust but also highly interpretable. Our approach offers potential prospect for the inclusion of GSD Ia in newborn screening. Rare diseases are underrepresented in machine learning studies and this work highlights the potential for these techniques, even in ultra-rare diseases such as GSD Ia.

The Gut Microbiome Regulates the Psychomotor Effects and Context-Dependent Rewarding Responses to Cocaine in Germ-Free and Antibiotic-Treated Animal Models.

Cocaine use disorder remains a major global health concern, with growing evidence that the gut microbiome modulates drug-related behaviors. This study examines the microbiome's role in cocaine-induced psychomotor activation and context-dependent reward responses using germ-free (GF) and antibiotic-treated (ABX) models. In GF mice, the absence of a microbiome blunted cocaine-induced psychomotor activation (p = 0.013), which was restored after conventionalization. GF mice also showed reduced cocaine-conditioned place preference (CPP) (p = 0.002), which normalized after conventionalization. Dopaminergic function, critical for psychomotor responses and reward, was microbiome-dependent, with increased dopamine levels (p = 0.009) and normalized turnover ratios after conventionalization. In the ABX model, microbiome depletion reduced both cocaine-induced locomotion and CPP responses (p ≤ 0.009), further supporting the role of gut microbes in modulating psychomotor and reward behaviors. ABX-treated mice also showed significant declines in microbial diversity, shifts in bacterial structure, and dysregulation in metabolic, immune, and neurotransmitter pathways (p ≤ 0.0001), including alterations in short-chain fatty acids and gamma-aminobutyric acid metabolism. These findings highlight the gut microbiome's critical role in regulating cocaine's psychomotor and rewarding effects, offering insights into potential therapeutic strategies for cocaine use disorder.

Linoleic acid alleviates aluminum toxicity by modulating fatty acid composition and redox homeostasis in wheat (Triticum aestivum) seedlings.

Lipids, as key components of biological membranes, play vital roles in sensing and initiating plant responses to various abiotic stresses. Here, the alteration of membrane fatty acids in wheat roots under Al stress was investigated using two genotypes differing in Al tolerance, and the role of linoleic acid in Al tolerance was comprehensively explored. Significant differences in the fatty acid profiles were observed, with increased linoleic acid accumulation in the Al-tolerant genotype. Supplementation with linoleic acid enhanced fatty acid synthesis, reduced membrane lipid saturation, improved membrane fluidity, and alleviated root growth inhibition. Wheat seedlings treated with linoleic acid exhibited a reduction in lipid peroxidation, as evidenced by decreased levels of malondialdehyde and lipid hydroperoxides. Furthermore, the application of linoleic acid increased the total contents and reduced forms of ascorbic acid (AsA) and glutathione (GSH), thereby restoring the cellular redox balance in wheat roots under Al stress. The elevated levels of AsA and GSH maintained by linoleic acid, can be attributed to the high efficiency of the AsA-GSH cycle, as linoleic acid enhanced the activities of the antioxidant enzymes involved. These results suggest that linoleic acid enhances wheat Al tolerance by maintaining both fatty acid synthesis and the levels of unsaturated fatty acids, as well as protecting membrane lipids from peroxidation by reactive oxygen species through the regulation of the AsA-GSH cycle.

Metabolic profiling reveals altered amino acid and fatty acid metabolism in children with Williams Syndrome

Williams Syndrome (WS) is a rare neurodevelopmental disorder with a prevalence of 1 in 7500 to 1 in 20,000 individuals, caused by a microdeletion in chromosome 7q11.23. Despite its distinctive clinical features, the underlying metabolic alterations remain largely unexplored. This study employs targeted metabolomics to investigate the metabolic characteristics of children with WS. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we identified significant dysregulation of 15 metabolites, with 11 upregulated and 4 downregulated. Notably, amino acids such as alanine, proline, and arginine were significantly elevated. Fatty acid metabolism showed pronounced upregulation of long-chain saturated fatty acids (C18:0, C20:0, C22:0, C24:0, C26:0, and C28:0) and downregulation of long-chain unsaturated fatty acids (C18:2 LA, C22:6 DHA, C16:1 PLA, and t-C18:1 EA), except for upregulated nervonic acid (C24:1) and arachidonic acid (C20:4). Metabolic pathway analysis highlighted disruptions in arginine synthesis, arginine/proline metabolism, alanine, aspartate and glutamate metabolism, biosynthesis of unsaturated fatty acids, linoleic acid metabolism, and arachidonic acid metabolism. This study provides the first comprehensive analysis of amino acid and fatty acid metabolism in children with WS, offering insights into the disorder’s complex metabolic landscape. Further validation in larger cohorts is essential to confirm these findings and their potential as biomarkers and therapeutic targets.

Proteomics, Metabolomics and Docking Analyses Provide Insights into Adaptation Strategies ofStaphylococcus warneri CPD1 to Osmotic Stress and Its Influence on Wheat Growth.

Staphylococcus warneri is a gram-positive mesophilic bacterium, resilient to extreme environmental conditions. To unravel its Osmotic Tolerance Response (OTR), we conducted proteomic and metabolomic analyses under drought (PEG) and salt (NaCl) stresses. Our findings revealed 1340 differentially expressed proteins (DEPs) across all treatments. Interestingly, majority of these DEPs were part of common pathways activated by S. warneri. CPD1 in response to osmotic stress. Notably, the bacterial isolate exhibited increased expression of lysophospholipases associated with biofilm formation and protection from environmental stresses, transglycosylases involved in peptidoglycan biosynthesis, and acetoin reductase linked to acetoin metabolism. The upregulation of global ion transporters, including ABC transporters, potassium ion transport, and glutamate transport, indicated the bacterium's ability to maintain ionic balance under stress conditions. Protein-protein docking analysis revealed highest interactions with thioredoxin and alpha-acetolactate decarboxylase, highlighting their crucial roles in the mechanisms of osmotic stress tolerance in S. warneri CPD1. Metabolomic results demonstrated significant alterations in fatty acids and amino acids. In the greenhouse experiment, the bacterial isolate significantly enhanced wheat biomass, nutrient content, photosynthesis, and proline levels under stress conditions, making it a promising bacterial inoculant and biostimulant for improving crop productivity in challenging environments.

Phase separation of MYB73 regulates seed oil biosynthesis in Arabidopsis.

MYB family transcription factors (TFs) play crucial roles in plant development, metabolism, and responses to various stresses. However, whether MYB TFs are involved in regulating fatty acid biosynthesis in seeds remains largely elusive. Here, we demonstrated that transgenic Arabidopsis (Arabidopsis thaliana) plants overexpressing MYB73 exhibit altered FATTY ACID ELONGATION1 (FAE1) expression, seed oil content, and seed fatty acid composition. Electrophoretic mobility shift assays (EMSAs) showed that FAE1 is a direct target of MYB73, and functional assays revealed that MYB73 represses FAE1 promoter activity. Transcriptomic analysis of the MYB73-overexpressing plants detected significant changes in the expression of genes involved in fatty acid biosynthesis and triacylglycerol assembly. Furthermore, MYB73 expression was responsive to abscisic acid (ABA), and ABA responsive element binding factor 2 (ABF2) directly bound to the ABA-responsive element (ABRE) in the MYB73 promoter to activate its expression. Additionally, we determined that MYB73 exhibits the hallmarks of an intrinsically disordered protein and forms phase-separated condensates with liquid-like characteristics, which are important in regulating target gene expression. Together, our findings suggest that MYB73 condensate formation likely fine-tunes seed oil biosynthesis.

Transcriptional and Metabolic Changes Following Repeated Fasting and Refeeding of Adipose Stem Cells Highlight Adipose Tissue Resilience.

Obesity and related metabolic disorders have reached epidemic levels, calling for diverse therapeutic strategies. Altering nutrient intake, timing and quantity by intermittent fasting seems to elicit beneficial health effects by modulating endocrine and cell signaling networks. This study explores the impact of cyclic nutrient availability in the form of every-other-day fasting (EODF) on human adipose stem cells (ASCs). We subjected ASCs to repeated fasting/refeeding (F/R) cycles, mimicking low glucose/high fatty acid (LGHF) conditions, and assessed phenotypic and transcriptomic changes, lipid storage capacity, insulin sensitivity, and differentiation potential. Four consecutive F/R cycles induced significant changes in adipogenic gene expression, with upregulation of FABP4 and PLIN1 during fasting, and increased lipid storage in the ASCs. Upon differentiation, ASCs exposed to LGHF conditions retained a transient increase in lipid droplet size and altered fatty acid metabolism gene expression until day 9. However, these changes dissipated by day 15 of differentiation, suggesting a limited duration of fasting-induced transcriptional and adipogenic memory. Despite initial effects, ASCs showed resilience, returning to a physiological trajectory during differentiation, with respect to gene expression and lipid metabolism. These findings suggest that the long-term effects of EODF on the ASC niche may be transient, emphasizing the ability of the adipose tissue to adapt and restore homeostasis.

A Comprehensive Analysis of Liver Lipidomics Signature in Adults with Metabolic Dysfunction-Associated Steatohepatitis-A Pilot Study.

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is the most common chronic liver disorder in Western countries, encompassing a range of conditions from steatosis to Metabolic Dysfunction-Associated Steatohepatitis (MASH), which can potentially progress to cirrhosis. Lipidomics approaches have revealed significant alterations in the hepatic lipidome associated with both steatosis and steatohepatitis, with these changes correlating with disease manifestation. While the transition from steatosis to MASH remains poorly understood, recent research indicates that both the quantity and quality of deposited lipids play a pivotal role in MASLD progression. In our study, we utilized untargeted and targeted analyses to identify intact lipids and fatty acids in liver biopsies from healthy controls and MASLD patients, categorized based on their histological findings. In total, 447 lipid species were identified, with 215 subjected to further statistical analysis. Univariate and multivariate analyses revealed alterations in triglyceride species and fatty acids, including FA 16:0, FA 16:1, FA 18:3 n6, the sum of MUFA, and the Δ9-desaturase activity ratio. This research provides insights into the connection between dysregulated lipid metabolism in the progression of MASLD, supporting previous findings. Further studies on lipid metabolism could improve risk assessment methods, particularly given the current limited understanding of the transition from steatosis to MASH.

Lipid Imbalance and Inflammatory Oxylipin Cascade at the Maternal-Fetal Interface in Recurrent Spontaneous Abortion

BackgroundRecurrent spontaneous abortion (RSA) is intricately linked to metabolic dysregulation at the maternal-fetal interface during early gestation. Abnormal levels of essential fatty acids and downstream oxylipins in decidua and chorionic villi have been identified as potential risk factors for RSA. Oxylipins have been linked to excessive inflammation, which might disrupt maternal-fetal immune tolerance, potentially contributing to RSA. Nonetheless, the exact fatty acid-oxylipin metabolic pathway at the matrernal-fetal interface in RSA occurrence remains unknown. Therefore, this research aimed to explore the effect of essential fatty acids, their transport, and downstream oxylipins at the maternal-fetal interface on RSA pathogenesis. MethodsPlasma, chorionic villus, and decidual tissue samples from the first trimester were collected from healthy pregnant women undergoing elective pregnancy terminations, as well as from patients experiencing spontaneous abortion. The concentrations of essential fatty acids and their downstream oxylipins in the villi and decidua were quantified using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS). The expression of enzymes related to metabolic pathways was investigated by q-PCR. The ratios of M1/M2 macrophages were assessed by flow cytometry (FCM). ResultsThis study found elevated concentrations of omega-6 fatty acids, encompassing arachidonic acid (AA), linoleic acid (LA), and dihomo-gamma-linolenic acid (DGLA) in maternal plasma and chorionic villi, whereas lower concentrations were observed in the decidua, than in samples from normal pregnancies. Further analysis revealed that the transport of these fatty acids was dysregulated at the maternal-fetal interface in RSA women, possibly due to the aberrant expression of the fatty acid translocase (FAT/CD36). In addition, this study revealed that RSA patients displayed higher levels of downstream oxylipins, such as prostaglandin F2a (PGF2a), prostaglandin E2 (PGE2), and leukotriene B4 (LTB4) in chorionic villi and decidua. These compounds may contribute to M1 inflammatory macrophage polarization in RSA, thereby forming a highly inflammatory environment and influencing immunomodulation at the maternal-fetal interface. ConclusionThe study revealed alterations in omega-6 fatty acids, CD36 transport, and AA downstream oxylipins in RSA, which in turn promote M1 macrophage polarization. Thus, this research has established a foundation for identifying potential biomarkers for, and providing novel insights into, the diagnosis and pathophysiology of RSA.

Associations of per- and polyfluoroalkyl substances with human milk metabolomic profiles in a rural North American cohort.

Per- and polyfluoroalkyl substances (PFAS) are a class of persistent synthetic chemicals that are found in human milk and are associated with negative health effects. Research suggests that PFAS affect both lactation and the human metabolome. We measured perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) in the milk of 425 participants from the New Hampshire Birth Cohort Study using liquid chromatography-tandem mass spectrometry (LC-MS/MS). A nontargeted metabolomics assay was performed using LC with high-resolution MS, and metabolites were identified based on in-house database matching. We observed six metabolic profiles among our milk samples using self-organizing maps, and multinomial logistic regression was used to identify sociodemographic and perinatal predictors of these profiles, including infant sex, parity, participant body mass index, participant age, education, race, smoking status, gestational weight gain, and infant age at time of milk collection. Elevated PFOA was associated with profiles containing higher amounts of triglyceride fatty acids, glycerophospholipids and sphingolipids, and carnitine metabolites, as well as lower amounts of lactose and creatine phosphate. Lower concentrations of milk PFOS were associated with lower levels of fatty acids. Our findings suggest that elevated PFOA in human milk is related to metabolomic profiles consistent with enlarged milk fat globule membranes and altered fatty acid metabolism. Further, our study supports the theory that PFAS share mammary epithelial membrane transport mechanisms with fatty acids and associate with metabolic markers of reduced milk production.

Palmitic acid and eicosapentaenoic acid supplementation in 3T3 adipocytes: impact on lipid storage and oxidative stress

ABSTRACT Objectives Obesity is a worldwide public health problem, predisposing individuals to serious cardiovascular and metabolic complications such as type 2 diabetes mellitus. White adipose tissue serves as an important regulator of energy balance, and its expansion in obesity can trigger inflammatory reactions and oxidative stress, which can also lead to insulin resistance. Adipocytes, with a key role in regulating metabolic homeostasis, respond to increased calorie intake and altered fatty acid composition with hypertrophy or hyperplasia. Of particular interest are saturated fatty acids such as palmitic acid and omega-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA), which have differential effects on adipocyte function and inflammation. Methods Using 3T3-L1 cells as a model for adipocytes, we evaluated the effects of PA and EPA on lipid accumulation, droplet size, and oxidative stress markers. Results We were able to show that EPA supplementation in 3T3 adipocytes does not lead to excessive lipid accumulation, but rather reduces the size of lipid droplets and also induces redox changes due to the unsaturated nature of EPA. Discussion These results emphasize the contrasting roles of PA and EPA and the importance of fatty acid composition in the regulation of adipocyte function.

Global deletion of the immune cell transcription factor, T-bet, alters gut microbiota and insulin sensitivity in mice.

The gut microbiota plays a role in energy homeostasis: its composition differs in lean and obese mice and may impact insulin sensitivity. The immune system has co-evolved with the gut microbiota, but direct regulation of microbial communities by the immune system and its metabolic impact is unclear. Mice lacking the immune cell specific transcription factor T-bet (Tbx21) are insulin sensitive. Compared with wild-type mice, T-bet deficient mice were found to have a higher proportion of colonic regulatory T cells despite significantly fewer colonic T cells, B cells and NK cells. Microbiota deletion by administration of antibiotics, increased colonic immune cell numbers. Furthermore, we report that T-bet -/- mice have an altered gut microbial composition and fecal short-chain fatty acid content, with an increase in butyrate production, compared with wild-type mice. Finally, in a proof-of concept study, we show that the enhanced insulin sensitivity observed in T-bet -/- mice is temporarily transmissible to antibiotic-treated wild-type mice through fecal transfer. Immune regulation of the gut microbiota by T-bet may be a novel pathway modulating insulin sensitivity.

Diet Biofunctionality in Modulating Cardiovascular Parameters in Obese Patients After Bioenteric Intragastric Balloon Bariatric Surgery.

Adiposopathy is the cause of many secondary disorders in the function and structure of many organs and systems in the body. In the progression of obesity and the increasing dysfunction of anti-inflammatory me-diators, chronic inflammation occurs. This may be accompanied by the development of metabolic complications. A diet with highly bioactive properties was formulated, and an element of diet therapy was introduced as a key component to support treatment in obese patients following bariatric surgery. Patients underwent a BIB (Bioenteric Intragastric Balloon) procedure. As obesity is a risk factor for cardiovascular diseases, this study aimed to regulate cardiovascular factors in adiposopathy. Anti-inflammatory dietary components with modulating properties were included, with increased bioflavonoids, vitamins A, E, C, folic acid, and synbiotics, and altered fatty acid composition. The results showed satisfactory effects on fat reduction and the regulation of isoprostanes, plasminogen, angiotensin, prostacyclin, triglycerides, blood pressure, and blood rheology parameters. Cardiovascular co-morbidities are common in obesity. This is due to the endocrine function of adipocytes. As such, we decided to investigate the possibility of using bioactive dietary components as an adjunct to the safety of reducing prothrombotic parameters in obese patients after BIB surgery. This study hypothesised that the enrichment of the recommended diet after bariatric surgery with the addition of n-3 EFAs, bioflavonoids, vitamins, and synbiotics might result in comparable or greater fat mass loss in the subjects. In addition, the use of a functional diet might show a beneficial modifying effect on antihyperglycemic parameter values. We then compared the results to those obtained among patients fed a reducing, standard diet. Using a functional diet, a significant reduction in visceral fat was achieved. A decrease in VFA was shown to reduce whole-blood viscosity. Furthermore, this study showed a significant effect of bioactive components on pro-thrombotic parameters in obese patients.

Characterization of pecan PEBP family genes and the potential regulation role of CiPEBP-like1 in fatty acid synthesis

Phosphatidyl ethanolamine-binding protein (PEBP) plays important roles in plant growth and development. However, few studies have investigated the PEBP gene family in pecan (Carya illinoinensis), particularly the function of the PEBP-like subfamily. In this study, we identified 12 PEBP genes from the pecan genome and classified them into four subfamilies: MFT-like, FT-like, TFL1-like and PEBP-like. Multiple sequence alignment, gene structure, and conserved motif analyses indicated that pecan PEBP subfamily genes were highly conserved. Cis-element analysis revealed that many light responsive elements and plant hormone-responsive elements are found in CiPEBPs promoters. Additionally, RNA-seq and RT-qPCR showed that CiPEBP-like1 was highly expressed during kernel filling stage. GO and KEGG enrichment analysis further indicated that CiPEBP-like1 was involved in fatty acid biosynthesis and metabolism progress. Overexpression of CiPEBP-like1 led to earlier flowering and altered fatty acid composition in Arabidopsis seeds. RT-qPCR confirmed that CiPEBP-like1 promoted fatty acid synthesis by regulating the expression of key genes. Overall, this study contributes to a comprehensive understanding of the potential functions of the PEBP family genes and lay a foundation to modifying fatty acid composition in pecan kernel.

Metabolomic Profiling of Open-Angle Glaucoma Etiologic Endotypes: Tohoku Multi-Omics Glaucoma Study.

The purpose of this study was to investigate biologically meaningful endotypes of open-angle glaucoma (OAG) by applying unsupervised machine learning to plasma metabolites. This retrospective longitudinal cohort study enrolled consecutive patients aged ≥20 years with OAG at Tohoku University Hospital from January 2017 to January 2020. OAG was confirmed based on comprehensive ophthalmic examinations. Among the 523 patients with OAG with available clinical metabolomic data, 173 patients were longitudinally followed up for ≥2 years, with available data from ≥5 reliable visual field (VF) tests without glaucoma surgery. We collected fasting blood samples and clinical data at enrollment and nuclear magnetic resonance spectroscopy to profile 45 plasma metabolites in a targeted approach. After computing a distance matrix of preprocessed metabolites with Pearson distance, gap statistics determined the optimal number of OAG endotypes. Its risk factors, clinical presentations, metabolomic profiles, and progression rate of sector-based VF loss were compared across endotypes. Five distinct OAG endotypes were identified. The highest-risk endotype (endotype B) showed a significant faster progression of central VF loss (P = 0.007). Compared with patients with other endotypes, those with endotype B were more likely to have a high prevalence of dyslipidemia, cold extremities, oxidative stress, and low OAG genetic risk scores. Pathway analysis of metabolomic profiles implicated altered fatty acid and ketone body metabolism in this endotype, with 34 differentially enriched pathways (false discovery rate [FDR] < 0.05). Integrated metabolomic profiles identified five distinct etiologic endotypes of OAG, suggesting pathological mechanisms related with a high-risk group of central vision loss progression in the Japanese population.

Lactobacillus Helveticus Improves Controlled Cortical Impact Injury-Generated Neurological Aberrations by Remodeling of Gut-Brain Axis Mediators.

Considerable studies augured the potential of gut microbiota-based interventions in brain injury-associated complications. Based on our earlier study results, we envisaged the sex-specific neuroprotective effect of Lactobacillus helveticus by remodeling of gut-brain axis. In this study, we investigated the effect of L. helveticus on neurological complications in a mouse model of controlled cortical impact (CCI). Adult, male and female, C57BL/6 mice underwent CCI surgery and received L. helveticus treatment for six weeks. Sensorimotor function was evaluated via neurological severity score and rotarod test. Long-term effects on anxiety-like behavior and cognition were assessed using the elevated-zero maze (EZM) and novel object recognition test (NORT). Brain perilesional area, blood, colon, and fecal samples were collected post-CCI for molecular biology analysis. CCI-operated mice displayed significant neurological impairments at 1-, 3-, 5-, and 7-days post-injury (dpi) and exhibited altered behavior in EZM and NORT compared to sham-operated mice. However, these behavioral changes were ameliorated in mice receiving L. helveticus. GFAP, Iba-1, TNF-α, and IL-1β expressions and corticotrophin-releasing hormone (CRH) levels were elevated in the perilesional cortex of CCI-operated male/female mice. These elevated biomarkers and decreased BDNF levels in both male/female mice were modified by L. helveticus treatment. Additionally, L. helveticus treatment restored altered short-chain fatty acids (SCFAs) levels in fecal samples and improved intestinal integrity but did not affect decreased plasma levels of progesterone and testosterone in CCI mice. These results indicate that L. helveticus exerts beneficial effects in the CCI mouse model by mitigating inflammation and remodeling of gut microbiota-brain mediators.