Search Results (15,249)

Biological activity of diets consisting of dietary fibers, peptides and polyphenols is largely mediated by the gut microbiota, which converts these compounds into bioactive metabolites. This review examines the microbiota–epigenome axis, highlighting gut microbiota-derived metabolites, including short-chain fatty acids (SCFAs), urolithins, and phenolic acids, that modulate host gene expression through DNA methylation, histone modifications, and non-coding RNA regulation. Current evidence from molecular and microbiome studies indicates that these metabolites influence key metabolic and inflammatory pathways, including lipid absorption via CD36, SIRT1 activation, and one-carbon metabolism involving folate and S-adenosylmethionine (SAM). Inter-individual variability in metabolic responses is associated with differences in microbial composition and metabotypes, which determine the magnitude of epigenetic regulation. Furthermore, dietary polyphenols derived from pomegranate, berries, tea, cocoa, and grapes are shown to modulate gut microbiota composition and enhance epigenetic effects. A “butyrate–polyphenol synergy” model is proposed, in which combined microbial metabolites optimize host epigenetic programming. Overall, agri-food by-products are suggested to function as modulators of the host epigenetic landscape, providing a framework for microbiome-targeted dietary strategies to improve metabolic and inflammatory health. Full article

Anthracnose, caused by Colletotrichum spp., is a major foliar disease limiting rubber tree (Hevea brasiliensis) productivity. To uncover resistance mechanisms, we compared resistant and susceptible germplasm using an integrated framework combining leaf structural analysis, physiological defense profiling, and transcriptome sequencing. Resistant germplasm exhibited lower stomatal density and more compact mesophyll, likely restricting pathogen entry and within-leaf spread. Following inoculation, resistant accessions showed stronger antioxidant responses, with higher activities of superoxide dismutase (SOD) and peroxidase (POD), and elevated phenylpropanoid-related enzymes, including polyphenol oxidase (PPO) and phenylalanine ammonia-lyase (PAL), peaking at 24–48 h post inoculation. These responses were accompanied by enhanced reactive oxygen species (ROS) accumulation (H₂O₂) but reduced lipid peroxidation (malondialdehyde), indicating efficient oxidative stress regulation. Microscopic observation revealed delayed infection progression and postponed differentiation of infection structures in resistant germplasm. Transcriptomic analysis further demonstrated that differentially expressed genes were mainly enriched in pathways related to signal transduction and secondary metabolism, particularly phenylpropanoid metabolism and related secondary metabolic pathways. Together, these results suggest that anthracnose resistance is mediated by coordinated structural barriers, redox homeostasis, and transcriptional regulation of defense networks. This study provides a mechanistic framework for resistance-oriented breeding and the utilization of resistant germplasm in rubber tree. Full article

Next-generation vaccines are being developed to elicit durable and cross-protective immune responses against diverse pathogens, particularly those targeting the respiratory and enteric systems. By strategically engaging T cell-centric antigen design, mucosal immune engagement, and induction of trained innate immunity, these innovative platforms are expected to reshape the paradigm of immunoprophylaxis and to offer promising avenues for enhanced protection against complex infectious diseases. Conventional antibody-based vaccines, though effective against many infections, often lack the capacity to induce durable or cross-protective immunity at mucosal surfaces. Advances in antigen design, delivery platforms, and adjuvant technologies now facilitate precise activation of tissue-resident memory T cells and enhancement of mucosal secretory IgA responses, thereby achieving sterilizing immunity at barrier surfaces while reinforcing systemic immune protection. Advanced delivery platforms, including lipid nanoparticles, viral vectors, and nano or liposomal carriers, further refine antigen presentation, enhancing stability, targeting, and overall immunogenicity. Concurrently, progress in understanding trained innate immunity highlights opportunities to induce broad, non-antigen-specific protection through epigenetic and metabolic reprogramming of innate cells. The integration of these adaptive and innate mechanisms may enhance early pathogen control, limits transmission, and strengthens defense against variant and antimicrobial-resistant pathogens across diverse populations. However, translating these immunological insights into safe, scalable, and globally accessible vaccines remains a major challenge. This review explores the emerging conceptual framework of next-generation vaccines that demonstrate partial integration of these axes in preclinical models, though human translation and functional synergy require Phase II validation. It highlights progress toward next-generation vaccines leveraging integrated adaptive and innate immune reprogramming for superior protection against respiratory and enteric pathogens. Full article

In this paper, we review the literature regarding metformin’s action on blood lipid concentrations in metformin-treated diabetic patients. Published data indicate that metformin reduces serum total cholesterol (T-C), LDL-cholesterol (LDL-C) and triacylglycerol (TAG) concentrations and raises serum HDL-cholesterol (HDL-C) concentrations in diabetic patients. The beneficial effect of metformin on serum lipid profiles in diabetic patients can result from (a) its action on AMP-activated protein kinase, which inhibits lipogenesis and cholesterol synthesis and stimulates fatty acid oxidation; (b) decreased plasma TAG concentrations, via promoting VLDL-TAG clearance by brown adipose tissue; (c) the inhibition of nuclear factor erythroid 2-related factor 2 (Nrf2) gene expression, affecting lipid profile in diabetic patients; (d) the inhibition of the expression of genes encoding proprotein convertase subtilisin/kexin 9 (PCSK9) and lipogenic enzymes; (e) the downregulation of carbohydrate-response element-binding protein (ChREBP), which affects liver TAG and cholesterol synthesis from acetate formed by gut microbiota; (f) the inhibition of angiopoietin-like 3 protein (ANGPTL3) gene expression, and consequent effects on plasma TAG concentrations; (g) the activation of AMPK, which inhibits LXRα activity; and (h) reverse cholesterol transport. In conclusion, one can assume that beyond its primary antihyperglycemic effect, metformin exerts pleiotropic effects that modulate lipid metabolism and blood lipid profile in T2D patients. These beneficial effects of metformin on blood lipid profile may play a role in the reduction in cardiovascular risk in diabetic patients. Full article

Background/Objectives: The etiology behind sex differences in the prevalence of abdominal aortic aneurysm (AAA) can only partly be explained by environmental factors such as smoking. Genetic factors are also likely to be part of the explanation since family history is common. We hypothesized that genetic factors on AAA prevalence might be different between the sexes. Methods: This study is designed as a case–control study with 83 female AAA patients, 101 female controls, 97 male AAA patients, and 196 male controls. Single nucleotide polymorphism (SNP) analysis was performed comparing 13 different SNPs. The selection of SNPs was based on previous SNP association studies, estrogen receptors, and SNPs important to inflammation and lipid metabolism, as these processes are modulated by estrogen. Results: A multivariable logistic regression resulted in significant differences in SNP association with AAA development between men and women in two SNPs (rs2010963 and rs8113877). Significant differences were found between cases and controls, using univariate analysis, in four SNPs: rs8113877 among women, and in rs6511720, rs2010963 and rs4988300 among men. No SNPs were significantly different compared to controls in both men and women. SNP rs8113877 is located in the promotor of the MMP-9 gene. Levels of circulating MMP-9 were measured in a subgroup of the study participants: an association between MMP-9 and AAA was found, and the association between rs8113877 and MMP-9 was sex-dependent. Conclusions: Genetic variability associated with AAA differs between men and women; these differences should be accounted for in future research. Full article

Background and Objectives: Diabetic peripheral neuropathy (DPN) is a common and debilitating complication of obesity and type 2 diabetes (T2D) affecting up to 50% of patients with long-standing disease. While chronic hyperglycemia plays a central role in its pathogenesis, intensive glycemic control provides only partial protection, suggesting the involvement of additional metabolic pathways. The primary objective of this systematic review was to evaluate the role of lipid metabolism disturbances and advanced lipidomic alterations in the development and progression of DPN in patients with obesity and T2D. Secondary objectives included identifying specific lipid species associated with DPN and exploring their potential pathophysiological and clinical implications. Methods: This systematic review included 8 studies that met the inclusion criteria and was conducted according to PRISMA guidelines and registered in PROSPERO/2026/CRD420261288920. Study quality was assessed using the Newcastle–Ottawa Scale. Results: Large population-based cohorts reported a consistent association between hypertriglyceridemia and DPN prevalence, with triglyceride levels >204 mg/dL associated with an approximately 40% increased risk. Lipidomic analysis revealed alterations in acylcarnitine, sphingolipids, and phospholipids. However, the evidence remains limited and heterogeneous, and neuropathy-specific outcomes were insufficiently evaluated in interventional studies. Conclusions: Lipid metabolism disturbances, particularly hypertriglyceridemia and specific lipidomic alterations, may contribute to DPN beyond the effects of hyperglycemia. Although not yet clinically actionable, lipidomic alterations may represent promising future biomarkers and therapeutic targets in DPN. However, the current evidence is limited by heterogeneity and predominantly observational designs. Further well-designed longitudinal and interventional studies are needed to clarify causal relationships and clinical relevance. Full article

Background: Plant essential oils are extensively utilized for their antimicrobial properties; however, the specific antifungal mechanisms of certain compounds are not well characterized. Geraniol, a naturally occurring monoterpene alcohol approved for use in foods, demonstrates potential efficacy against spoilage fungi, yet detailed mechanistic insights are lacking. Methods: In this study, we determined the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of geraniol against P. polonicum. We assessed the underlying mechanisms by evaluating membrane integrity, intracellular leakage, reactive oxygen species (ROS), antioxidant enzymes (superoxide dismutase [SOD], peroxidase [POD], catalase [CAT]), malondialdehyde (MDA) levels, ATP content, and ATPase activity. Inoculated yam slices were exposed to geraniol vapor, and we monitored sensory, physicochemical, enzymatic, and microbial parameters. Results: Geraniol exhibited a minimum inhibitory concentration/minimum fungicidal concentration (MIC/MFC) of 0.3 mL/L. It disrupted cellular membranes, induced leakage, generated ROS, and caused lipid peroxidation, leading to elevated levels of malondialdehyde (MDA). Additionally, geraniol activated antioxidant enzymes and impaired energy metabolism. Fumigation with geraniol dose-dependently delayed the deterioration of yam, reduced weight loss, preserved texture and color, inhibited polyphenol oxidase (PPO) and POD activities, enhanced CAT and SOD activities, lowered MDA levels, and suppressed bacterial growth. Conclusions: Geraniol inhibits P. polonicum through multiple mechanisms, including membrane disruption, oxidative stress, and interference with energy metabolism, thereby effectively preserving the quality of fresh-cut yam and demonstrating potential as a natural preservative. Full article

Age-related changes in the gut significantly impact host health, yet the multi-omics dynamics during the maturation of Tibetan pigs remain unclear. This study aimed to investigate the morphological, microbial, metabolic, and transcriptomic transformations in the intestines of aging Tibetan pigs. We analyzed the ileum and colon of 1-year-old and 3-year-old Tibetan pigs using histological evaluation, 16S rRNA sequencing, metabolomics, and transcriptomics. Aging to 3 years significantly improved ileal architecture, notably increasing the villus height to crypt depth ratio. Older pigs exhibited higher colonic microbial diversity, a decreased Firmicutes to Bacteroidota ratio, and enrichment of homeostasis-associated taxa, including Lactobacillus, Prevotellaceae, and Ruminococcaceae. Metabolomics revealed higher abundance of certain metabolites, including docosahexaenoic and arachidonic acids, enriching lipid metabolism and bile secretion pathways. Transcriptomics identified 2363 differentially expressed genes in the ileum, primarily involved in immune regulation and nutrient digestion. Integrated analysis showed strong positive correlations between enriched microbes (Lactobacillus porci) and up-regulated host genes (UGT2B31, CCL28) governing intestinal homeostasis. The transition from 1 to 3 years of age in Tibetan pigs fosters a synergistic host-microbiome environment, enhancing intestinal barrier function, immune capacity, and metabolic efficiency. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent global health concern. Although pharmacotherapies such as Resmetirom and semaglutide have recently gained approval by FDA/EMEA, therapeutic options remain limited, necessitating the exploration of novel natural compounds. Our previous research indicated that lycopene exerts protective effects against MASLD; however, its underlying molecular mechanisms remain incompletely understood. The present study aimed to investigate whether lycopene alleviates MASLD by modulating mitophagy, with a focus on the PINK1/Parkin pathway. C57BL/6J mice were fed with high-fat diet for 12 weeks to induce MASLD and daily gavage of lycopene (10/40 mg/kg). In vitro, AML12 cells were treated with lycopene and Mdivi-1 to assess the role of PINK1/Parkin-mediated mitophagy against lipid accumulation, oxidative stress, and apoptosis. The results found that lycopene supplementation significantly ameliorated HFD-induced weight gain, dyslipidemia, hepatic steatosis, pathological liver injury, and elevated serum liver enzymes. It reduced hepatic reactive oxygen species (ROS) overproduction and suppressed the mitochondrial apoptotic pathway, as evidenced by decreased cytochrome c release and caspase cascade activation. Concurrently, lycopene restored ATP levels and mitochondrial membrane potential, improved ultrastructural integrity, and balanced mitochondrial dynamics by downregulating DRP1 and upregulating MFN2 and OPA1. Crucially, lycopene activated PINK1/Parkin-mediated mitophagy, leading to an increased LC3-II/LC3-I ratio and Beclin1 expression, alongside decreased levels of mitochondrial proteins TOM20 and COX IV. In vitro, the lycopene partially reversed the exacerbating effects of Mdivi-1 on lipid accumulation, ROS generation, apoptosis, and the suppression of the PINK1/Parkin pathway. Collectively, lycopene ameliorates MASLD by activating PINK1/Parkin-mediated mitophagy and improving mitochondrial homeostasis, thereby reducing hepatic lipid accumulation and attenuating hepatocyte apoptosis. Full article

Heat stress (HS), increasingly intensified by climate change, severely restricts tomato growth and productivity. Although core heat shock factor-mediated transcriptional networks have been extensively characterized, how lipid metabolic reprogramming is transcriptionally coordinated during thermotolerance remains unclear. Using SlHDZ19 overexpression and mutant lines together with transcriptomic, biochemical, promoter-binding, and gene-silencing analyses, we show that the homeobox-leucine zipper transcription factor SlHDZ19 promotes tomato (Solanum lycopersicum) thermotolerance by activating a PLA2-dependent lipid-metabolic transcriptional program in leaves. SlHDZ19 overexpression generally improved heat-stress performance, while SlHDZ19 mutant lines exhibited heightened sensitivity, including more severe wilting, higher electrolyte leakage, and reduced proline accumulation and CAT activity under heat stress. Transcriptomic analysis revealed that SlHDZ19 is required for the full induction of canonical heat-responsive genes and that the linoleic acid metabolism pathway was repeatedly implicated in SlHDZ19-dependent transcriptional changes. SlHDZ19 binds to and activates the promoters of SlPLA_2α, which encodes a phospholipase A2 involved in releasing linoleic acid from membrane lipids, and three lipoxygenase genes (SlLox7, SlLox8, and SlLoxC), accompanied by elevated overall PLA2 and LOX activities in SlHDZ19-overexpressing plants. Moreover, genetic silencing of SlPLA_2α in both wild-type and SlHDZ19-overexpressing backgrounds supported its functional requirement downstream of SlHDZ19 in thermotolerance. Collectively, our findings support a thermotolerance module in which SlHDZ19 transcriptionally regulates PLA2- and LOX-associated steps of linoleic acid metabolism, potentially linking lipid-associated signaling and membrane remodeling with heat stress adaptation in tomato. Full article

Background/Objectives: Intermittent fasting (IF) has been widely investigated for its metabolic effects, including improvements in insulin sensitivity, lipid metabolism, and inflammatory markers. However, its psychological and experiential dimensions remain comparatively underexplored. The present narrative review examines IF within a psychobiological framework, integrating evidence from metabolic science, neuroendocrinology, and affective neuroscience to explore its potential impact on emotional regulation and interoceptive processes. Methods: A structured narrative literature search was conducted across PubMed, Scopus, and Google Scholar, focusing on studies published between 2010 and 2025. Eligible studies included human and relevant animal research addressing metabolic, hormonal, interoceptive, and psychological responses to IF. Evidence was synthesized thematically to identify convergent mechanisms linking metabolic adaptations to emotional and regulatory outcomes. Results: Available literature suggests that IF is associated with a metabolic shift toward lipid utilization, characterized by increased ketone body production, particularly β-hydroxybutyrate. These adaptations appear to be accompanied by modulation of neuroendocrine pathways and may influence central nervous system functioning through mechanisms potentially related to neuroinflammation, mitochondrial efficiency, and synaptic plasticity. Emerging evidence further suggests that IF may modulate BDNF signaling and gut–brain axis activity, although direct causal pathways in humans remain to be established. At the psychological level, IF is associated with heterogeneous emotional outcomes: structured fasting protocols have been linked to modest improvements in perceived stress and mood in metabolically healthy individuals, whereas irritability, anxiety, or behavioral rigidity may emerge in those with pre-existing psychological vulnerabilities. Individual differences in interoceptive sensitivity, emotion regulation strategies, and moderating biological factors—including sex, circadian timing, and habitual physical activity—appear to influence these responses. Conclusions: Overall, IF may be conceptualized as a context-dependent psychobiological stressor whose effects extend beyond metabolic regulation to include interoceptive and emotional processes. These effects appear bidirectional, potentially promoting psychological resilience in some individuals while increasing the risk of affective destabilization or maladaptive behaviors in others. Current evidence remains limited by a lack of integrative and longitudinal studies combining metabolic and psychological measures. Future research adopting multidisciplinary approaches is needed to clarify the mechanisms underlying individual variability and to better define the potential benefits and risks of IF in both clinical and non-clinical populations. Full article

Background: Gestational diabetes mellitus (GDM) is associated with metabolic disturbances extending beyond glucose homeostasis, including alterations in lipid metabolism. However, evidence on the fatty acid composition of maternal serum lipids in GDM remains inconsistent, and data on placental fatty acid transfer are limited. This study aimed to explore associations between maternal serum lipid fatty acid composition, selected FA indices, and transplacental transfer of fatty acids derived from maternal serum lipids in pregnancies complicated by GDM. Methods: A cross-sectional study was conducted among 139 pregnant women, including 104 healthy controls and 35 women with GDM. Maternal serum and umbilical cord blood samples were collected at delivery. FA composition was analyzed using gas chromatography. Selected FA indices and the transplacental transport index (TTI) were calculated. Statistical analyses included group comparisons, multivariable models adjusted for maternal age and pre-pregnancy BMI, and false discovery rate correction. Results: Modest differences were observed in selected fatty acids and FA indices, particularly palmitoleic acid (C16:1) and the C16:1/C16:0 ratio. Principal component analysis suggested partial separation between groups, although substantial overlap was present. A difference in transplacental transport was observed for α-linolenic acid; however, high variability was noted. No consistent associations between reported dietary patterns and fatty acid composition of circulating serum lipids were identified. Conclusions: This exploratory study suggests potential differences in fatty acid composition and selected indices in GDM; however, findings should be interpreted with caution. The observed patterns may reflect late-pregnancy metabolic adaptations rather than causal mechanisms. Further studies in larger and more diverse populations are required to confirm these findings. Full article

This study evaluated the effects of dietary Elionurus muticus essential oil (EMEO) on growth performance, physiological responses, and resistance to car transport stress in Nile tilapia (Oreochromis niloticus). Fish were fed experimental diets for 60 days and subsequently subjected to 6 h of transport stress. Five diets were tested: 0.00 (control), 0.25, 0.50, 1.00, and 1.50 mL EMEO kg⁻¹, in triplicate (10 fish per 500 L tank; stocking density 0.4 kg L⁻¹). Citral was the major EMEO compound (73.91%). Increasing dietary EMEO levels improved growth performance and reduced the feed conversion ratio. Before transport, EMEO supplementation increased erythrocyte counts and plasma glucose levels, while reducing hematocrit and hepatic aspartate aminotransferase (AST) activity (p < 0.05). After transport, plasma glucose, hematocrit, and hepatic AST values decreased, whereas hepatic glycogen and hemoglobin levels increased with higher EMEO inclusion (p < 0.05). Also, post-transport, EMEO-fed fish showed enhanced intestinal digestive enzyme activity (lipase and amylase) and antioxidant capacity (superoxide dismutase and ferric reducing antioxidant power) but increased protein carbonyl levels. Lipid peroxidation (malondialdehyde) was reduced at intermediate EMEO levels (p < 0.05). Histological analyses indicated no tissue damage and suggested improved liver and intestinal function with increasing EMEO inclusion. Overall, dietary supplementation with 1.00 mL EMEO kg⁻¹ is recommended to enhance growth performance and metabolic adjustment and to improve physiological status to withstand transport stress in Nile tilapia. Full article

Chronic intermittent hypoxia (CIH), the cardinal pathophysiological feature of obstructive sleep apnea, is increasingly recognized as an important modifier of metabolic dysfunction-associated steatotic liver disease (MASLD), but the underlying mechanisms remain incompletely understood. In this study, male C57BL/6 mice were fed a standard diet or a high-fat diet (HFD) and exposed to normoxia or CIH for 8 weeks. Histological, ultrastructural, biochemical, transcriptomic, proteomic, and metabolomic analyses were integrated to characterize hepatic alterations induced by CIH under metabolic stress. CIH markedly aggravated HFD-induced liver injury, as evidenced by increased body fat, hepatomegaly, serum transaminases, steatosis, mitochondrial ultrastructural alterations, and inflammatory infiltration. Mechanistically, CIH promoted hepatic lipid metabolic reprogramming by suppressing the PPARα/CPT1A fatty acid β-oxidation axis while enhancing the SREBP-1c/FASN/PLIN2 lipogenic pathway, impaired the Nrf2/HO-1/SLC7A11/GPX4 antioxidant defense system, increased lipid peroxidation and iron accumulation, and activated NF-κB/NLRP3 signaling. These findings support a multifactorial model in which CIH functions as an additional hypoxic stressor that exacerbates HFD-induced MASLD-like liver injury through coordinated metabolic, oxidative, and inflammatory dysregulation. Full article

Patients with liver cancer frequently exhibit abnormal liver function and disorders in lipid metabolism. This study investigates the effects of Oleanolic acid (OA) on hepatocellular carcinoma (HCC) through the regulation of lipid metabolism. Computational simulations identified six core targets of OA, including PPARα, HMGCR, and ESR1, with stable binding confirmed through molecular docking and dynamics analyses. The experiments demonstrated that OA reduced intracellular lipid accumulation, suppressed cell migration (p < 0.05), and promoted apoptosis. The levels of lipid droplets and triglycerides (TG) were significantly decreased (p < 0.05). The expression levels of lipid metabolism-related genes, including PPARA, CPT1A, FASN, and HMGCR, were assessed using qRT-PCR (p < 0.05). Additionally, protein expression levels were analyzed through Western blotting (p < 0.05). Furthermore, the combination of OA with the antagonist GW6471 enhanced tumor suppression, while the combination with the agonist Pemafibrate reversed the effects of OA. Compared to OA alone, the antagonist combination significantly reduced PPARα and CPT1A protein expression (p < 0.05), whereas Pemafibrate upregulated these proteins (p < 0.05). In conclusion, OA exerts its anti-lipid metabolism effects in HCC by modulating the PPARα-CPT1A axis, indicating its potential therapeutic value in liver cancer treatment. Full article