Search Results (268)

Kidney transplant recipients face a substantial burden of premature mortality and morbidity, primarily due to persistent inflammation, cardiovascular risk, and nutritional deficiencies. Traditional nutritional interventions in this population have either focused on supplementing individual nutrients—often with limited efficacy—or required comprehensive dietary overhauls that compromise patient adherence. In this narrative review, we explore the rationale for dietary nut enrichment as a feasible, multi-nutrient strategy tailored to the needs of kidney transplant recipients. Nuts, including peanuts and tree nuts with no added salt, sugar, or oil, are rich in beneficial fats, proteins, vitamins, minerals, and bioactive compounds. We summarize the multiple post-transplant challenges—including obesity, sarcopenia, dyslipidemia, hypertension, immunological dysfunction, and chronic inflammation—and discuss how nut consumption may mitigate these issues through mechanisms involving improved micro-nutrient intake (e.g., magnesium, potassium, selenium), lipid profile modulation, endothelial function, immune support, and gut microbiota health. Additionally, we highlight the scarcity of randomized controlled trials in high-risk populations such as kidney transplant recipients and make the case for studying this group as a model for investigating the clinical efficacy of nuts as a nutritional intervention. We also consider practical aspects for future clinical trials, including the choice of study population, intervention design, duration, nut type, dosage, and primary outcome measures such as systemic inflammation. Finally, potential risks such as nut allergies and oxalate or mycotoxin exposure are addressed. Altogether, this review proposes dietary nut enrichment as a promising, simple, and sustainable multi-nutrient approach to support cardiometabolic and immune health in kidney transplant recipients, warranting formal investigation in clinical trials. Full article

The pathogenesis of idiopathic pulmonary fibrosis (IPF) involves complex interactions between epithelial, mesenchymal, immune, and endothelial cells, often aggravated by lipid metabolism dysfunction, mitochondrial, and peroxisomal abnormalities. Changes in lipid metabolism may drive fibrotic processes, suggesting the potential of lipid biomarkers for disease monitoring. We compared here the cholesterol metabolism and very-long-chain fatty acid profiles of patients with IPF with healthy controls. The IPF patients’ lipidic profiles were also evaluated according to disease severity and progression rate. This prospective, observational study involved 50 IPF patients at disease diagnosis before antifibrotic treatment initiation and 50 age- and gender-matched healthy controls. Using a serum lipidomic profile, we focused on cholesterol synthesis, mitochondrial and peroxisomal markers, inflammatory lipids, and oxidative stress markers. Disease severity was evaluated using the Gender-Age-Physiology (GAP) index, while the prognosis was assessed by classifying patients as rapid or slow progressors based on a 24-month follow-up. IPF patients exhibited lower levels of cholesterol synthesis precursors (e.g., lathosterol), mitochondrial oxysterols, and inflammatory mediators (e.g., arachidonic acid) compared to controls. Reduced levels of these biomarkers were also associated with higher disease severity and rapid disease progression. Conversely, some peroxisomal markers (e.g., brassidic acid and nervonic acid) showed altered trends depending on disease severity. Our findings indicate that patients with IPF, compared to healthy controls, may show lipidomic alterations, particularly a reduction in cholesterol precursors and docosahexaenoic acids, which are also associated with IPF severity and progression. While preliminary, this study suggests lipidomics to be a promising tool to stratify IPF severity and prognosis. Full article

Background: X-ALD is a white matter (WM) disease caused by mutations in the ABCD1 gene encoding the transporter of very-long-chain fatty acids (VLCFAs) into peroxisomes. Strikingly, the same ABCD1 mutation causes either devastating brain inflammatory demyelination during childhood or, more often, progressive spinal cord axonopathy starting in middle-aged adults. The accumulation of undegraded VLCFA in glial cell membranes and myelin has long been thought to be the central mechanism of X-ALD. Methods: This review discusses studies in mouse and drosophila models that have modified our views of X-ALD pathogenesis. Results: In the Abcd1 knockout (KO) mouse that mimics the spinal cord disease, the late manifestations of axonopathy are rapidly reversed by ABCD1 gene transfer into spinal cord oligodendrocytes (OLs). In a peroxin-5 KO mouse model, the selective impairment of peroxisomal biogenesis in OLs achieves an almost perfect phenocopy of cerebral ALD. A drosophila knockout model revealed that VLCFA accumulation in glial myelinating cells causes the production of a toxic lipid able to poison axons and activate inflammatory cells. Other mouse models showed the critical role of OLs in providing energy substrates to axons. In addition, studies on microglial changing substates have improved our understanding of neuroinflammation. Conclusions: Animal models supporting a primary role of OLs and axonal pathology and a secondary role of microglia allow us to revisit of X-ALD mechanisms. Beyond ABCD1 mutations, pathogenesis depends on unidentified contributors, such as genetic background, cell-specific epigenomics, potential environmental triggers, and stochasticity of crosstalk between multiple cell types among billions of glial cells and neurons. Full article

Obesity and cardiometabolic diseases (CMDs) have reached epidemic levels. Dysregulation of lipid metabolism is a risk factor for obesity and CMDs. Lipids are energy substrates, essential components of cell membranes, and signaling molecules. Fatty acids (FAs) are the major components of lipids and are classified based on carbon chain length and number, position, and stereochemistry of double bonds. They exert differential impacts on CMDs, such that saturated fat increases risks while very-long-chain n-3 FAs provide benefits. The functionalities of FAs, modulating membrane properties, acting as ligands for receptors, and serving as precursors for lipid mediators, are vital for insulin signaling, lipid metabolism, oxidative stress, and inflammatory response, collectively contributing to cardiometabolic health. This review examines recent advances in the characteristics and functional properties of different FAs in lipid structures, signaling pathways, and cellular metabolism to better understand the differential roles of different types of FAs in obesity and cardiometabolic health. Full article

Background: Very-long-chain acyl-CoA dehydrogenase deficiency (VLCADD) is caused by biallelic pathogenic variants in ACADVL (acyl-CoA dehydrogenase very-long-chain), leading to impaired fatty acid oxidation and the accumulation of long-chain acylcarnitine. We report a single case of a two-year-old girl, whose neonatal metabolic screening revealed an acylcarnitine profile suggestive of VLCADD, with residual enzymatic activity of 19.8%. Methods: We performed ACADVL whole-gene sequencing. We then carried out an in silico analysis of the potential effects of the variants with dedicated tools, assessing splicing, RNA structure, RNA binding factors, and protein structure. We also conducted gene expression analysis. Results: Genetic testing identified her as compound heterozygous for the pathogenic ACADVL variant (NM_000018.3):c.848T>C, inherited from her mother, and for the two paternal variants, c.-64T>C in the basal promoter and c.957G>A, a synonymous substitution in exon 10. Gene expression analysis revealed reduced ACADVL mRNA levels in the proband’s blood cells but without abnormal isoform production. A decreased expression of the paternal allele carrying the 957A was also observed. Despite this significant reduction in mRNA levels, the underlying mechanism remains unclear. Conclusions: Although currently healthy, due to the VLCAD residual activity within the range associated with the mild form of the disease, the child might be at potential risk for metabolic decompensation or late-onset VLCADD. Our results indicated an allelic imbalance in mRNA expression and c.957G>A is identified as a hypomorphic allele. This suggests that deep ACADVL sequencing is a valuable tool for correlating genetic variants with enzymatic activity levels. Full article

The detection of elevated long-chain acylcarnitine levels, particularly C14:1 and the C14:1/C2 ratio, during neonatal screening may indicate very-long-chain acyl-CoA dehydrogenase deficiency (VLCADD), although similar findings can result from postnatal starvation. We investigated the relationship between false-positive results, postnatal weight loss, and subsequent growth. Additionally, we explored potential diagnostic markers of postnatal starvation. The following neonates from Oita Prefecture (April 2014–March 2024) were included in this study: patients identified as false-positive for VLCADD (n = 19), patients with VLCADD (n = 3), and children negative in mass screening who completed their 3-year-old health check-up (n = 30). The false-positive group exhibited significant weight loss at blood sampling for neonatal screening. An acylcarnitine analysis showed significant increases in various short- to long-chain fatty acids in the false-positive group, likely owing to enhanced fatty acid catabolism via β-oxidation. Elevation of a broad range of fatty acids and reduced amino acid levels seemed to be associated with significant weight loss at blood sampling. Full article

Deep-sea chemosynthetic ecosystems, including cold seeps and hydrothermal vents, are widely spread in global oceans. Campylobacterota are important primary producers in deep-sea hydrothermal vents and serve as a vital food source for local invertebrates. However, the nutrients that these bacteria can provide to their hosts are unclear. To date, research on Campylobacterota in cold seeps is very limited. Consequently, little is known about the biological features and ecological potential of Campylobacterota in cold seeps. In the present work, we examined the diversity, growth, metabolic characteristics, and nutrient production of Campylobacterota in a deep-sea cold seep. Over 1000 Campylobacterota ASVs, especially autotrophic Sulfurovum and Sulfurimonas, were identified. By optimizing the culture medium, 9 Sulfurovum and Sulfurimonas strains were isolated, including three potentially novel species. Two novel species were characterized and found to exhibit unique morphological features. These two novel strains possessed complete reverse tricarboxylic acid pathways. One novel strain, FCS5, was a psychrotolerant autotroph with denitrification and phosphorus-removing capacity. FCS5 could grow in the absence of vitamins. Consistently, metabolomics and transcriptome analyses indicated that FCS5 produced multiple vitamins, which regulated the expressions of a large number of genes associated with carbon fixation and multiple-nutrient synthesis. Besides vitamins, autotrophic Campylobacterota also produced abundant free amino acids, fatty acids (short-chain, medium, and long-chain), and proteins. This study indicates that the cold seep abounds with Campylobacterota, which are capable of providing various nutrients for the chemosynthetic ecosystem. In addition, these bacteria may have wide applications, such as in wastewater treatment and carbon emission reduction. Full article

Proteins for elongation of very long-chain fatty acids (ELOVLs) are critical for the synthesis of long-chain polyunsaturated fatty acids (LC-PUFAs), and they are one group of the rate-limiting enzymes responsible for the initial condensation reaction within the fatty acid elongation. Elovl8 is a newly identified member of the ELOVL protein family, and its evolutionary and functional characterizations are still rarely reported. Here, we identified two elovl8 paralogues (named Scelovl8 and Scelovl8b) from Chinese perch (Siniperca chuatsi), and then their molecular and evolutionary characteristics, as well as potential roles involved in LC-PUFA biosynthesis, were examined. The ORFs of both Scelovl8a and Scelovl8b genes were 810 bp and 789 bp in length, encoding proteins of 270 and 263 amino acids, respectively. Multiple protein sequence comparisons indicated that elovl8 genes were highly conserved in teleosts, showing similar structural function domains. Meanwhile, phylogenetic analysis showed that the elovl8 gene family was clustered into two subclades of elovl8a and elovl8b, and Scelovl8a and Scelovl8b shared close relationships with banded archerfish elovl8a and striped bass elovl8b, respectively. Genetic synteny and gene structure analyses further confirmed that elovl8b is more conserved in comparison to elovl8a in teleosts. In addition, Scelovl8a was found to be highly expressed in the liver, while Scelovl8b was most abundant in the gills. Long-term food deprivation and refeeding are verified to regulate the transcription of Scelovl8a and Scelovl8b, and intraperitoneal injection of fish oil (FO) and vegetable oil (VO) significantly modified their gene expression as well. In summary, our results in this study indicate that elovl8 genes were conservatively unique to teleosts, and both elovl8 genes might be involved in the endogenous biosynthesis of LC-PUFAs in Chinese perch. These findings not only expand our knowledge on the evolutionary and functional characteristics of both elovl8 genes but also lay a solid basis for investigating regulatory mechanisms of LC-PUFA biosynthesis in various teleosts. Full article

Significant deviations between chronological and biological age can signal the early risk of chronic diseases, driving the need for tools that accurately determine biological age. While DNA methylation-based clocks have demonstrated strong predictive power for biological aging determination, their clinical application is limited by several barriers including high costs, the need to analyze hundreds of methylation sites using sophisticated platforms and the lack of standardized measurement tools and protocols. In this study, we developed a multivariate linear model using the analysis of eight CpGs within the promoter region of the very long chain fatty acid elongase 2 gene (ELOVL2). The model generated predicts biological age with a mean absolute error (MAE) of 5.04, providing a simplified, cost-effective alternative to more complex methylation-based clocks. Additionally, we identified sex-specific biological clocks, achieving MAEs of 4.37 for males and 5.38 for females, highlighting sex-related molecular differences in the methylation of this gene during aging. Our minimal CpG-based clock offers a practical solution for estimating biological age, with potential applications in clinical practice for assessing age-related disease risks and providing personalized healthcare interventions. Full article

Endometrial cancer (EC) is a complex gynecologic malignancy that requires a deeper understanding of its molecular basis to improve therapeutic strategies. In this study, we investigated the role of fatty acid (FA) reprogramming in the progression of EC. We analyzed FA profiles to identify the stage-specific changes and gene expression profiles of key enzymes involved in FA synthesis, desaturation, elongation, transport, and oxidation at different stages of EC. Our results show that EC tissues have lower levels of saturated FA and branched-chain FA, higher levels of very long-chain FA, n-3 polyunsaturated FA (PUFA), and monounsaturated FA, with the exception of myristoleic acid. The differences in n-6 PUFA were inconsistent. Gene expression analysis revealed the upregulation of key enzymes controlling de novo FA synthesis, including ACACA, FASN, SCD1, and ELOVL1. In contrast, the expression of genes related to FA transport in the cell and β-oxidation was downregulated. The expression of some genes related to PUFA metabolism was upregulated, while others were downregulated. These results demonstrate a reprogramming of lipid metabolism in EC tissues and suggest potential targets for novel therapeutic interventions in EC. Full article

Very-long-chain acyl-CoA dehydrogenase deficiency (VLCADD) is due to a defect in metabolism of long-chain fatty acids. Infants with VLCADD may experience cardiomyopathy, hypoglycemia, or even death; thus, early detection and intervention is crucial. The spectrum of disease and natural variation in newborn metabolism, however, lead to overlap in acylcarnitine values between affected and unaffected individuals, which contributes to the difficulty in identifying true positive cases while minimizing false positive cases. VLCADD was added to the state of Wisconsin’s newborn screening (NBS) panel in 2000. A previous retrospective review of VLCADD screen positive cases identified between 2000 and 2014 resulted in a change to the screening algorithm. Following implementation, a reduction in the percentage of false positive screens from 25.3% to 20.4% was observed between 2015 and 2021. The overall PPV also decreased, from 37.2% to 28%, due to an increase in the number of carriers identified (27.5% of cases in 2000–2014 and 51.8% of cases in 2015–2021). A data review also identified three long-chain acylcarnitine elevations (C14:1, C14:1/C16, and C14:1/C2) that had statistically significant differences in concentrations in true positive populations versus false positive populations. Utilization of the C14:1, C14:1/C16, and C14:1/C2 values in newborn screening may provide clearer distinction between true positive and carrier populations and additionally increase the PPV of this screen. Full article

β-ketoacyl CoA synthase (KCS) is a key enzyme in the synthesis of long-chain fatty acids. It affects plant stress resistance by regulating the chain length of fatty acid elongation products, the wax deposition in plant epidermis, and the formation of suberization layers. Through a comprehensive, genome-wide analysis, we identified members of the melon KCS (CmKCS) family and characterized their sequence features, phylogenetic relationships, and expression profiles under three abiotic stress conditions, employing bioinformatics tools and methods. Fifteen CmKCSs were identified in the melon genome and found to be unevenly distributed across eight chromosomes. The subcellular localization of most members is located on the cytoplasmic membrane and chloroplasts. The CmKCS family amplifies its members in a tandem repeat manner, which is more closely related to the cucumber KCS and has similar gene functions. Subfamilies I, IV, and VI exhibit variations in conserved domain sequences, which may indicate specific functional differentiation. The promoter region harbors various cis-acting elements related to plant hormones and abiotic stress responses. Among these, the most abundant are elements responsive to abscisic acid, methyl jasmonate, salicylic acid, and anaerobic induction. CmKCS5, CmKCS6, CmKCS10, and CmKCS12 showed high expression in autotoxicity, saline-alkali stress, and microplastic exposure environments. These four CmKCSs may play important roles in melon development and stress response. In conclusion, this study provides a comprehensive analysis of the CmKCS gene family, revealing its potential roles in melon’s response to abiotic stresses and laying a foundation for further functional characterization of these genes in stress tolerance mechanisms. Full article

Living systems require energy to maintain their existence and perform tasks such as cell division. This energy is stored in several molecular forms in nature, specifically lipids, carbohydrates, and amino acids. At a cellular level, energy is extracted from these complex molecules and transferred to adenosine triphosphate (ATP) in the cytoplasm and mitochondria. Within the mitochondria, fatty acid β-oxidation (FAO) and oxidative phosphorylation (OXPHOS) are crucial metabolic processes involved in generating ATP, with defects in these pathways causing mitochondrial disease. Very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) is a fatty acid β-oxidation disorder (FAOD) affecting 1 to 2 individuals per 100,000. Similar to other mitochondrial disorders, there is no cure for VLCADD, with symptomatic treatment comprising dietary management and supplementation with medium-chain fatty acids to bypass the enzyme deficiency. While this addresses the primary defect in VLCADD, there is growing evidence that other aspects of mitochondrial function are also affected in VLCADD, including secondary defects in OXPHOS function. Here, we review our current understanding of VLCADD with a focus on the associated biochemical and molecular defects that can disrupt multiple aspects of mitochondrial function. We describe the interactions between FAO proteins and the OXPHOS complexes and how these interactions are critical for maintaining the activity of both metabolic pathways. In particular, we describe what is now known about the protein–protein interactions between VLCAD and the OXPHOS supercomplex and how their disruption contributes to overall VLCADD pathogenesis. Full article

The Agrobacterium fabrum C58 is a phytopathogen able to infect numerous species of cultivated and ornamental plants. During infection, bacteria genetically transform plant cells and induce the formation of tumours at the site of invasion. Bacterial cell wall components play a crucial role in the infection process. Lipopolysaccharide is the main component of Gram-negative bacteria’s outer leaflet of outer membrane. Its lipophilic part, called lipid A, is built of di-glucosamine backbone substituted with a specific set of 3-hydroxyl fatty acids. A. fabrum incorporates a very long chain hydroxylated fatty acid (VLCFA), namely 27-hydroxyoctacosanoic acid (28:0-(27OH)), into its lipid A. A. fabrum C58 mutants deprived of this component due to mutation in the VLCFA’s genomic region, have been characterised. High-resolution mass spectrometry was used to establish acylation patterns in the mutant’s lipid A preparations. The physiological properties of mutants, as well as their motility, ability to biofilm formation and plant infectivity, were tested. The results obtained showed that the investigated mutants were more sensitive to environmental stress conditions, formed a weakened biofilm, exhibited impaired swimming motility and were less effective in infecting tomato seedlings compared to the wild strain. Full article

This article represents the first consideration of the peculiarities of the fatty acid (FAs) composition and structure of storage triacylglycerols (TAGs) of the relict plant Lunaria rediviva L. The composition of storage TAGs was found to comprise 21 individual FAs, with an unsaturated FA content of 96.8%. Additionally, monounsaturated acids with a very long chain (VLCFAs), specifically C20:1–C24:1, constituted over 60% of the total FAs. The ethylene bond position isomers of unsaturated FAs were accurately identified and the presence of unusual isomers, including 20:1$\Delta$13, 22:1$\Delta$15, and 24:1$\Delta$17 acids. Furthermore, the unusual minor 24:2$\Delta$15,18 acid was identified and characterised for the first time. The pathways of the mentioned VLCFA’s biosynthesis have been proposed. The distribution of FA acyls between the sn positions of triacylglycerols was found to be highly specific. Thus, VLCFAs exclusively acylate the $\alpha$ positions of the carbon atoms of the glycerol residue of the TAG molecule (sn-1 and sn-3 positions), while unsaturated C18 acids exclusively acylate the $\beta$-carbon atom (sn-2 position). The composition of the molecular species of TAGs was analysed using a calculation method based on the Vander Wal model and by RP-HPLC-ESI-MS. A significant discrepancy from the statistical model was observed, indicating a preference for the formation of symmetrical TAGs, such as sn-1,3-dierucoyl-2-oleoyl-glycerol and related molecular species. This observation led to the formulation of a hypothesis regarding the potential existence of at least two specialised enzyme isoforms involved in the biosynthesis of such TAGs via the Kennedy pathway, exhibiting unusual substrate specificity. Consequently, this plant can be regarded not only as a producer of unusual molecular types of triacylglycerols but also as a source of genetic material for the search of genes encoding the aforementioned enzymes with unusual substrate specificity. Full article