Metabolites最新文献

Background: Fatty acid oxidation disorders (FAOD) are rare inborn errors of metabolism that impair mitochondrial β-oxidation and energy production. Management includes fasting avoidance for all FAOD types. Patients with long-chain FAOD are advised to restrict long-chain triglycerides (LCTs) to 10% of total energy intake and supplement medium-chain triglycerides (MCTs). The impact of such dietary modification on fat-soluble vitamin status has not yet been studied. Methods: In this cross-sectional study, serum concentrations of vitamins A, 25(OH)D, E, and β-carotene were measured in 36 FAOD patients and 36 healthy controls matched for age and sex. Vitamins A, E, and β-carotene were quantified using high-performance liquid chromatography and vitamin 25(OH)D through an immunoassay. FAOD patients were further divided into fat-modified (LCT-restricted) and standard-fat diet subgroups based on dietary management. Results: FAOD patients had significantly higher vitamin A concentrations than controls (p < 0.05), while there was no difference in vitamins 25(OH)D, E, and β-carotene. Within the FAOD cohort, the fat-modified group had higher levels of vitamins A and 25(OH)D but lower levels of vitamin E and β-carotene than the standard-fat group (all p < 0.05). Vitamin 25(OH)D deficiency (<20 ng/mL) was more frequent in the standard-fat group (p = 0.03). Conclusions: Fat-modified diets influence fat-soluble vitamin status in FAOD, emphasising the importance of ongoing monitoring and tailored supplementation. Future work should focus on optimising nutritional management, including modifications to formula composition, and on addressing the currently limited evidence on nutritional status and vitamin deficiencies in patients with FAOD.

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Background: This study evaluated the effects of rumen-protected choline (RUPCHOL) supplementation in dairy cows from 21 days before calving to 28 days postpartum. The objective was to determine how RUPCHOL influences metabolic status, milk composition, and subsequent calf growth until weaning.

Methods: Twenty-seven pregnant Holstein cows were assigned to a Control group (n = 13) or an RUPCHOL group (n = 14), both receiving a total mixed ration (TMR), with the RUPCHOL group supplemented with 15 g/day of choline chloride. Cows were monitored during prepartum, calving, and postpartum periods for body weight, body condition score, dry matter intake, rectal temperature, milk yield and composition, and blood metabolites.

Results: RUPCHOL supplementation tended to reduce serum aspartate aminotransferase and lowered concentrations of non-esterified fatty acids and β-hydroxybutyrate, indicating improved metabolic status. Milk total solids, fat, and protein percentages were higher in RUPCHOL-fed cows, suggesting enhanced milk quality. Maternal supplementation did not affect colostrum immunoglobulin G (IgG) content or calf body weight and body measurements (heart girth, wither height, hip height, and body length) from birth to weaning.

Conclusions: In summary, RUPCHOL supplementation improved indicators of metabolic health and milk composition of dairy cows during the peripartum period without altering calf growth outcomes.

The tumor heterogeneity that is frequently observed in cancer tissues comprises not only cancer cells but also stromal cells in the tumor microenvironment. One of the major components of tumor stroma, i.e., cancer-associated fibroblasts (CAFs), play crucial roles in tumor progression and the tumor response to chemotherapy. The known subtypes of CAFs are antigen-presenting CAFs (apCAFs), myofibroblastic CAFs (myCAFs), and inflammatory CAFs (iCAFs). It has been speculated that (i) the heterogeneity of CAF subtypes might contribute to tumor progression; (ii) cell-to-cell interactions among CAF subtypes in tumors might be associated with the development of various types of carcinomas, and (iii) juxtracrine and/or paracrine signaling from CAFs may play important roles in this development. A clarification of the mechanisms that underlie the tumoral heterogeneity of CAFs could contribute to cancer treatment as precision medicine. This review explains the significance of CAF heterogeneity in tumor microenvironments, especially concerning the CAF subtypes.

Background: The Camellia genus is widely recognized for its remarkable diversity in floral morphology and coloration, with Camellia petelotii (Merr.) Sealy being particularly notable for its rare golden-yellow flowers, which possess exceptional ornamental value. Despite its horticultural significance, the molecular mechanisms governing its flowering process remain poorly elucidated, presenting a substantial barrier to effective conservation and breeding initiatives. Methods: To address this knowledge gap, we conducted a comprehensive transcriptomic analysis, focusing on three distinct developmental stages of C. petelotii floral organs: the alabastrum stage (S1), the half-opened flower stage (S2), and the full bloom stage (S3). These samples were subjected to high-throughput sequencing using the Illumina platform. Following rigorous quality control and alignment with the reference genome, we performed transcript assembly and integrated comprehensive gene annotation data with quantitative gene expression profiles. Results: Our analysis identified 18,732 differentially expressed genes (DEGs) showing significant expression changes across developmental stages. Notably, we identified 134 DEGs as potential flowering-related genes, which were functionally associated with key pathways involved in floral regulation, including plant hormone signal transduction (e.g., AUX/IAA, ARF, SAUR, GH3, JAR4, GID1 and SOC1), starch (SS, SUS, BAM) and sucrose metabolism (HK, FrK, and GH32), circadian rhythm regulation (e.g., PIF3, ELF3, LHY, and PRR), and the Autonomous pathway. Building upon these findings, we have proposed a comprehensive model illustrating the regulatory network underlying flowering transition in C. petelotii. The reliability of the transcriptomic data was demonstrated through the validation of 11 genes using quantitative real-time PCR (qRT-PCR). Conclusions: These insights not only enhance our understanding of the molecular basis of flowering in this species but also provide a valuable theoretical framework for future genetic improvement and breeding programs of C. petelotii.

Background: Traditional machine-learning approaches face challenges when attempting to integrate diverse biological information for predicting metabolite-disease relationships. The intricate connections linking metabolites, diseases, proteins, and Gene Ontology (GO) annotations present substantial obstacles for conventional pairwise graph representations, which prove inadequate for modeling such complex multi-way interactions. Methods: An innovative hypergraph-based framework (DHG-LGB) was developed to exploit this complexity through conceptualizing diseases as hyperedges. Within this architecture, individual hyperedges link multiple vertices including metabolites, proteins, and GO annotations, thereby enabling richer representation of the biological networks underlying metabolite-disease relationships. Metabolite-disease relationships were encoded as low-dimensional vectors through hypergraph neural network (HGNN) operations incorporating Laplacian smoothing and message propagation mechanisms. LightGBM (LGB) was used to construct a model for identifying the potential metabolite-disease associations. Results: Under 5-fold cross-validation, DHG-LGB achieved 98.87% accuracy, 91.77% sensitivity, 99.58% specificity, 95.60% precision, Matthews correlation coefficient (MCC) of 0.9305, receiver operating characteristic area under curve (AUC) of 0.9983, and precision-recall area under curve (AUPRC) of 0.9860. The framework maintained strong performance when tested with varying positive-to-negative ratios (spanning 1:1 through 1:10), consistently achieving AUC values exceeding 0.9954 and AUPRC values above 0.9820, thereby confirming excellent robustness and generalization capability. Comparative evaluations against existing methodologies verified the superiority of DHG-LGB. Conclusions: The DHG-LGB framework delivers more comprehensive modeling of biological interactions relative to conventional approaches and substantially enhances predictive accuracy for metabolite-disease relationships. It is foreseeable that it will be a valuable computational tool for biomarker identification and precision medicine initiatives.

Background/objectives: Exercise calorimetry provides a means to quantify the relative contributions of lipid and carbohydrate (CHO) oxidation across a range of exercise intensities. Although lipid oxidation capacity has been widely studied-particularly in relation to exercise prescription for individuals with obesity-the factors governing CHO oxidation during exercise are less clearly defined. This study therefore aimed to investigate, within a large single-center cohort, not only the established determinants of maximal lipid oxidation (LIPOXmax) but also those influencing CHO oxidation.

Methods: Exercise calorimetry was performed in a cohort of 6465 individuals (4561 women and 1904 men; mean age 46.5 years; mean BMI 33.6 kg/m²). Two principal physiological indices were derived: LIPOXmax, defined as the exercise intensity eliciting maximal rates of fat oxidation, and the carbohydrate cost of the watt (CCW), defined as the slope characterizing the relationship between CHO oxidation and power output.

Results: LIPOXmax showed positive associations with lean and muscle mass, and negative associations with fat mass and age, supporting the notion that greater muscle mass enhances the capacity for fat oxidation. Although men demonstrated higher absolute maximal fat oxidation rates, adjustment for body composition revealed that women exhibited relatively higher lipid oxidation (+30%, p < 0.001), occurring at a greater percentage of V˙O_2max (+9.2%, p < 0.001). Furthermore, the carbohydrate cost of the watt was significantly elevated in women (+17.8% compared with men). CCW was positively correlated with BMI, fat mass, and age, and negatively correlated with muscle mass, LIPOXmax, and the crossover point-that is, the exercise intensity at which CHO becomes the predominant substrate.

Discussion and conclusions: Individuals with higher adiposity exhibited a greater reliance on carbohydrate oxidation, whereas leaner individuals preferentially oxidized lipids at comparable exercise intensities. These observations reinforce the reciprocal interplay between lipid and carbohydrate metabolism during exercise and highlight the substantial influence of body composition, age, and sex. Notably, this study provides the first comprehensive characterization of the determinants of CHO oxidation during exercise, identifying sex, age, and adiposity as major contributing factors. This underexplored facet of metabolic flexibility may hold practical relevance in clinical contexts such as obesity or susceptibility to exercise-induced hypoglycemia.

Background/Objectives: Reduced serotonin transporter (SERT) function is associated with increased vulnerability to emotional and metabolic dysregulation, particularly in elderly women. Most preclinical studies relied on young male rodents with complete Sert deficiency; the Western diet (WD) acerbates these abnormalities. However, complete Sert loss does not fully reflect the human condition of partial SERT dysfunction. Here, we examined the effects of WD in aged female Sert^+/- mice on metabolic, biochemical, molecular, and behavioral outcomes. Methods: Wild-type (WT) and Sert^+/- mice were fed WD or a control diet. Emotionality, cognition, glucose tolerance (GT), plasma ¹HNMR spectroscopy metabolome and biochemical parameters were studied. Gene expression analyses of nitric oxide (NO)-related markers were performed in the hypothalamus, dorsal raphe, and liver. Results: WD-exposed WT mice showed impaired GT and reduced plasma lactate and branched-chain amino acid levels; metabolome changes were more pronounced in mutants, while GT was unchanged. Naïve Sert^+/- mice exhibited lower lactate and alanine levels compared with WT controls. WD increased leptin and cholesterol levels in both genotypes, whereas triglyceride concentrations were reduced in Sert^+/- mice. Both WD and Sert deficiency increased Nos expression, while arginase expression was differentially regulated by genotype and diet. Malondialdehyde levels were elevated in the prefrontal cortex of Sert^+/- mice regardless diet. WD also impaired object recognition memory and induced anxiety- and depression-like behaviors, with more pronounced effects in Sert^+/- mice, except marble test behavior. Conclusions: Partial Sert deficiency aggravates some but not all WD-induced metabolic alterations, enhances oxidative stress, dysregulates arginine-NO signaling, and modifies behavior, highlighting the translational relevance of Sert^+/- mice for modeling SERT dysfunction.

Background/Objectives: Chronic heat stress impairs lipid mobilization from adipocytes, which reduces substrate availability for muscle metabolism. Systemic inflammation is a key facilitative response to heat stress, and we sought to determine if mitigating inflammation in heat-stressed wether lambs would improve lipid flux. Methods: Two cohorts of commercial feedlot lambs were heat stressed for 30 days. In study 1, heat-stressed lambs received dexamethasone injections every 3 days, fish oil capsules twice daily, or no intervention. In study 2, heat-stressed lambs received daily boluses of ω-3 polyunsaturated fatty acid Ca²⁺ salts (ω-3 PUFA) or no intervention. Results: In both studies, heat stress reduced ex vivo epinephrine-stimulated free fatty acid and glycerol mobilization from visceral adipose tissue. These deficits were partially resolved by fish oil and fully resolved by ω-3 PUFA. In study 1, fish oil recovered heat stress-induced deficits in circulating triglycerides and HDL-cholesterol but not in circulating free fatty acids. Fish oil and dexamethasone resolved the increase in muscle PPARα, indicating less lipid utilization for metabolism. In study 2, ω-3 PUFA resolved heat stress-induced deficits in muscle CD36 and PPARγ, indicating improved lipid uptake capacity. However, interventions did not resolve reduced intramuscular lipid content in either study. Conclusions: We conclude that inflammation was a primary facilitator of impaired lipid mobilization in heat-stressed lambs but was not the sole driver of lipid dysregulation. Nevertheless, targeting inflammation was a beneficial strategy for improving lipid flux during chronic heat stress.