Diets high in simple carbohydrates and saturated fats increase the risk of liver diseases. Gamma oryzanol (ORY), a compound found in rice bran, shows promise in addressing metabolic liver diseases, though its impact on lipid pathways requires further exploration. This study evaluated the effects of ORY in rats submitted to a high sugar-fat (HSF) diet using a multiomics approach to unravel its impact on lipid metabolism and associated pathways. Male Wistar rats were fed a control (CTRL), HSF, or HSF + ORY (0.5% w/w) diet for 30 weeks. Hepatic lipid profiling was performed using high-resolution mass spectrometry. Proteins and lipids were integrated into molecular pathway analyses. miR-122 expression was assessed by qRT-PCR, while oxidative stress markers were measured via colorimetric assays. The HSF diet altered 233 lipids compared to CTRL, while ORY supplementation modulated 84 lipids relative to the HSF group, with 39 lipids showing opposing regulatory profiles. Integrating proteomic data revealed key pathways in MAFLD pathophysiology affected by ORY. Additionally, ORY regulated miR-122 expression linked to lipid metabolism and reduced oxidative stress, demonstrating its potential to mitigate HSF-induced liver damage. ORY modulates hepatic lipid profiles and influences integrated metabolic networks, suggesting a significant role in MAFLD prevention and treatment.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-26929-7.

Restoration of glucose metabolic homeostasis for treating CNS diseases: mechanistic insights and potential clinical prospect.

Sphingosine-1-phosphate signaling in respiratory diseases: mechanisms and therapeutic perspectives.

Poplar-driven biomes recruitment stabilizes soil micro-food webs under Mollisols degradation: Insights from multi-trophic interactions and metabolic networks

Synergistic sulfur-iron redox in novel composite biofilm carriers drives efficient mixotrophic denitrification and phosphate removal: Metagenomic insights into nitrogen/sulfur metabolic networks and microbial interactions.

Integrated multi-omics and network pharmacology reveals antioxidant-active metabolites and health benefits of Camellia oleifera seed oil.

Lead (Pb), a pervasive environmental toxicant, exerts substantial nephrotoxic effects in mammalian organisms. However, the molecular mechanisms underlying Pb-induced renal toxicity remain poorly elucidated. In this study, we employed an integrative bioinformatics approach to identify pivotal hub genes associated with Pb nephrotoxicity through comprehensive analysis of the GEO data set GSE59913. Comparative transcriptomic analysis of renal tissues from PbAc₂-exposed (600 mg/kg) and control rats identified 541 differentially expressed genes (DEGs), showing predominant enrichment in response to xenobiotic stimulus, signal transduction, and response to toxic substance. Multilayer pathway analysis revealed significant convergence on metabolic homeostasis networks, PI3K-Akt, AMPK, MAPK, Jak-STAT, PPAR, and cytokine-cytokine receptor interaction pathways. Utilizing protein-protein interaction networks, we identified ten pivotal hub genes implicated in Pb-induced nephrotoxicity-including IL6 (interleukin 6), CDK1 (cyclin-dependent kinase 1), and CCNA2 (cyclin-A2)-which are functionally associated with IL-17, JAK-STAT, TNF signaling, DNA replication, and cell cycle regulation pathways. This study provides the mechanistic framework for Pb nephrotoxicity, uncovering potential therapeutic targets for environmental heavy metal toxicity.

Dynamics of the Spanish fir transcriptome in nature: Metabolic pathways and gene networks involved in the response to climate stress

Complementary-synergistic Fe-Ce bimetallic nanozyme enhances antimicrobial efficacy through intermodule cycling catalysis.

Blood meal modulates midgut bacterial community structure and metabolic function in Aedes albopictus.

Integration of metagenomics and targeted metabolomics reveals the flavor metabolism network of the microbial community in traditional watermelon soybean paste.

Advances in microbial nitrogen metabolism: synergizing technological innovations to drive systems biology and sustainable biotechnology.

Efficient valorization of starch-rich food waste for methane recovery: Targeted bioaugmentation of propionate-degrading methanogenic consortia and synergistically regulated metabolic networks

Geographical flavor fingerprinting of morels: integrated analysis of volatile and non-volatile components with environmental drivers across Chinese regions.

Myokine-mediated muscle-organ interactions: Molecular mechanisms and clinical significance.

Reverse-tracing unravels microbial succession and flavor stratification driven by vertical physicochemical gradients in Zaopei fermentation.

Background/Objectives: Type 2 diabetes mellitus (T2DM) is a major metabolic disorder and is frequently accompanied by liver steatosis. Apolipoprotein J (ApoJ) is a glucose-regulated molecular chaperone that has been implicated in hepatic lipid deposition under nutrient overload. This study aimed to investigate the role of hepatocyte-specific ApoJ deletion in hepatic metabolism under diabetic conditions. Methods: A T2DM mouse model with hepatocyte-specific ApoJ knockout (HKO) was established through a high-fat diet combined with streptozotocin injection. Hepatic metabolic profiles were analyzed using untargeted metabolomics with UHPLC–MS/MS. Differential metabolites were subjected to KEGG pathway and Sankey diagram analyses to identify biologically relevant pathways. Results: In total, 140 metabolites showed significant differential abundance in HKO mouse liver, primarily encompassing organic acids and derivatives as well as lipids and lipid-like molecules. KEGG analysis revealed that ApoJ deletion enhanced pathways related to vitamin digestion and absorption, thiamine metabolism, amino acid biosynthesis, lysine degradation, and 2-oxocarboxylic acid metabolism. In contrast, pathways associated with galactose metabolism, cysteine and methionine metabolism, purine metabolism, and the pentose phosphate pathway were suppressed. Sankey diagram analysis further demonstrated that ApoJ deletion markedly reshapes hepatic metabolic networks in T2DM. Conclusions: Given the central role of hepatic dysmetabolism in the pathogenesis of diabetes and its complications, targeting ApoJ may represent a promising therapeutic approach for restoring hepatic metabolic homeostasis and preventing diabetes-associated steatosis.

ABSTRACT Ulcerative colitis (UC) is a chronic inflammatory disease of the human colon. Dysbiotic gut microbiota play a central role in its pathogenesis, and alterations in microbial composition and function are closely linked to disease activity. Humanized gnotobiotic mice are increasingly used to study how dysbiotic, human-derived microbial communities shape intestinal inflammation. However, the fidelity of microbiota engraftment and its impact on host physiology and metabolism remain incompletely understood. In this study, we performed a multiomics analysis following fecal microbiota transfer (FMT) from eight patients with active UC into germ-free C57BL/6N mice (five mice per donor). The mice were monitored over three weeks. Longitudinal analysis of microbial communities was performed using 16S rRNA (bacteria) and ITS2 (fungi) amplicon sequencing. Microbial metabolic flux was inferred via genome-scale metabolic modeling, and plasma metabolites were assessed by targeted metabolomics. We observed donor-specific physiological changes in recipient mice, including variations in body weight and adipose tissue. Spontaneous colonic inflammation occurred in one group and was subsequently linked to unintended transfer of Clostridioides difficile, which was previously clinically unrecognised in the donor. While bacterial engraftment overall was generally donor-specific and stable across mice, fungal taxa were transferred inconsistently and at low abundance. Despite similar overall plasma metabolomic profiles, select metabolites, including 3-indoleacetic acid, were differentially associated with specific microbial taxa. Moreover, metabolic modeling revealed disrupted metabolic exchange networks in the mouse microbiota compared to the original human donor communities. In conclusion, while human FMT into germ-free mice reliably transmits bacterial features, it introduces metabolic alterations and fails to fully reproduce the fungal microbiome. These findings underscore the need for cautious interpretation of microbiota-driven effects in gnotobiotic models and highlight the limitations of current approaches in replicating the full complexity of human gut ecosystems.

Cancer metabolism is gaining considerable attention. Tumor cells are characterized by a peculiar metabolic state to sustain the continuous demand of energy and metabolites needed for their proliferation and long-term survival. Such metabolic alterations extend beyond cancer cells, affecting multiple components of the tumor microenvironment (TME), including immune cells, stromal cells, and endothelial structures, and are influenced by both local and systemic conditions. Mast cells (MCs) are innate immune cells capable of both pro- and anti- tumorigenic functions and with the potential to modulate the activity of bystander immune cells. Nevertheless, despite their established importance in the TME, the impact of MCs in modulating cancer metabolism remains largely unexplored. This review outlines current findings regarding the metabolic conditions in the TME that modulate MC function, and, vice versa, how MC-derived metabolites can influence tumor progression, acting both on cancer and stromal cells. We focus on four main altered conditions in the TME: glucose metabolism, amino acid availability, lipid composition, and hypoxia. As studies investigating MC metabolism in cancer are limited, we also discuss relevant literature addressing how metabolic stimuli influence MC activity, as well as the effects of MC-derived metabolites on target cells, in non-cancer physiological or pathological conditions, to highlight possible mechanisms that deserve further investigation in cancer settings. Deeper investigation of MC-related metabolic networks in the TME is needed, not only to elucidate their functional modulation in response to current metabolic interventions, but also to explore their potential as therapeutic targets in the context of cancer metabolism.

Nilaparvata lugens is a migratory pest with high fecundity and outstanding drug resistance, which poses a devastating danger to rice production. This study investigated the reproductive regulation mechanism of N. lugens, specifically silencing the trehalose-6-phosphate synthase gene (TPS) via RNAi to elucidate how TPS governs the trehalose metabolic network through modulation of trehalose biosynthesis. Insect fecundity hinges on the synchronized progression of oogenesis and the tightly controlled expression of vitellogenin (Vg). In N. lugens, this coordination is orchestrated by an integrated molecular network that converges juvenile hormone signaling (JH), 20-hydroxyecdysone pathways (20E), insulin/IGF signaling (IIS), and the target of rapamycin cascade (TOR), collectively dictating the reproductive output of the species. Using TPS knockdown as the entry point, this study dissects the lipid-metabolic circuitry of N. lugens and uncovers how hormonal signaling cascades orchestrate reproduction by precisely modulating vitellogenin (Vg) and its cognate receptor VgR. Synthesized double-stranded terpene synthase genes (dsTPSs) can degrade mRNA, inhibit protein translation, and ultimately lead to the silencing of TPS genes, simultaneously crippling energy provision and hormonal signaling to orchestrate a multi-pronged suppression of reproduction. This dual-action intervention offers a promising molecular target for environmentally friendly management of N. lugens.