Search Results (3,371)

This study evaluated the effects of replacing soybean meal with fermented dried tomato pomace (FDTP) on biochemical, immune, and antioxidant responses, meat quality, and hepatic transcriptomic profiles in Boer goats. Twenty-four male goats were assigned to a control diet or diets in which FDTP replaced 33.33% (T1), 66.66% (T2), or 100% (T3) of soybean meal for 60 days (n = 6). Serum biochemical parameters, total immunoglobulin, and alternative complement hemolytic activity were unaffected, whereas lysozyme activity increased linearly with FDTP replacement. FDTP increased muscular SOD1 expression and altered cytokine expression in a tissue-specific manner, including increased IL10 and reduced IL1B and TNFα expression in selected tissues. In gastrocnemius muscle (n = 3), T2 had higher collagen content and lower cooking loss than the control and T3, whereas T3 had higher drip loss than T2; selected textural properties were also altered. During refrigerated storage, lipid oxidation was affected by storage day but not by treatment or the treatment × day interaction. T2 was selected post hoc for exploratory hepatic transcriptomic comparison with the control (n = 5). Among 587 DEGs, significantly enriched KEGG pathways involved metabolism and biotransformation, including steroid hormone biosynthesis, retinol metabolism, bile secretion, xenobiotic metabolism, and pentose and glucuronate interconversions. In addition to the enriched pathways, PI3K–Akt, MAPK, NF-κB, and cytokine–cytokine receptor pathways contained DEGs related to metabolic, stress, and immune responses. Overall, FDTP replacement was associated with changes in selected immune and meat-quality traits and with hepatic transcriptional responses predominantly related to metabolic and biotransformation processes. Full article

Aging populations worldwide face increasing burdens from physiological deterioration. Bioactive peptides derived from milk proteins have attracted interest for their biological activities, yet systematic evidence against aging remains limited. Here, we investigated casein hydrolysates in a D-galactose-induced murine aging model. Following eight weeks of oral administration at graded doses, we quantified systemic oxidative stress markers, inflammatory cytokine profiles, hepatic and cerebral histopathology, and multiple immune competence parameters. Our data demonstrate that casein peptides dose-dependently suppressed lipid peroxidation, elevated endogenous antioxidant enzyme activities, and rebalanced cytokine networks toward an anti-inflammatory state. Concurrently, peptide treatment attenuated tissue lesions in both liver and brain, while restoring thymus and spleen indices, normalizing T-cell subset distributions, and recovering serum immunoglobulin levels. These findings indicate that oral administration of the casein hydrolysate peptide preparation was associated with improvements in redox homeostasis, inflammatory status, tissue integrity, and immune function in D-galactose-induced aging mice. This work provides mechanistic insights into casein peptides as a multi-target protective agent against age-associated physiological decline, supporting further exploration of their therapeutic potential in aging biology. Full article

The dried fruits of Ligustrum lucidum Ait. are well-established in East Asian medicine for hepatoprotection. Given this ethnopharmacological precedent and their close taxonomic kinship, we hypothesized that the fruit polysaccharide of its horticultural congener, Ligustrum × vicaryi L. (LVFP), may confer analogous hepatic benefits. We assessed LVFP in a murine model of acute liver injury (ALI) induced by lipopolysaccharide and D-galactosamine (LPS/D-GalN) to test this hypothesis. LVFP pretreatment significantly mitigated hepatic pathological damage, normalized serum aminotransferases (AST, ALT), and reversed lipid peroxidation (reduced MDA, elevated SOD). Simultaneously, LVFP reduced pro-inflammatory cytokines, including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), and corrected lipid metabolic abnormalities (CHO, TG). To decode these phenotypic rescues, network pharmacology and molecular docking nominated a 10-gene hub signature (featuring KDR (binding energy = −8.65 kcal/mol), AKT1, GSK3B, and IL2). we further found that this signature—particularly KDR and PKM—robustly discriminates ALI from controls (AUC = 1.00; AUPR = 0.848), supporting its disease relevance. Collectively, these findings support our initial hypothesis that LVFP exerts multi-dimensional hepatoprotection. Full article

Background: Uveal melanoma (UM) typically metastasizes to the liver for yet unclear reasons. Hepatic steatosis influences metastasis in several cancer entities, and increased lipid synthesis and metabolism in the cancer tissue promotes tumor progression. The aim of this study was to investigate the association of MRI-derived lipid content in non-tumorous liver tissue and liver metastases with the biological behavior and metastatic characteristics of UM liver metastases, as well as with survival in patients with metastatic UM. Methods: The lipid content in the liver and hepatic metastases was quantified by multiparametric magnetic resonance imaging in 46 patients with metastasized UM prior to therapy. The perfusion characteristics of liver metastases were assessed using contrast-enhanced MRI-derived arterial enhancement ratios (metastasis-to-aorta signal intensity ratio), and diffusion-weighted imaging was used to evaluate tissue cellularity in metastatic tissues. Results: We found a significant correlation between body mass index (BMI) and hepatic lipid content (Spearman’s r = 0.47; unadjusted p = 0.0027; adjusted p = 0.03; 95% CI: 0.17 to 0.69), between the hepatic lipid content and volume of the metastases (Spearman’s r = −0.42; unadjusted p = 0.007; adjusted p = 0.036; 95% CI: −0.65 to −0.12) after correction for multiple testing. Higher hepatic lipid content (≥5%) was associated with improved survival with stage IV (p = 0.00043), whereas metastatic lipid content showed no significant association in Kaplan–Meier analysis. In Cox proportional hazards analysis, higher hepatic lipid content was associated with reduced hazard ratio of death independent of tebentafusp treatment (without tebentafusp: p = 0.0034; HR = 0.497; with tebentafusp: p = 0.0016; HR = 0.318) while no consistent association was observed for metastatic lipid content. Conclusions: Metabolic changes associated with a high BMI may contribute to lipid-induced changes in the liver microenvironment that may play a role in the tumor biology of hepatic metastases in patients with UM. Full article

Edible mushroom polysaccharide (EMP) preparations have repeatedly improved glycemic control, adiposity, lipid homeostasis and hepatic lipid accumulation in animal models, and luminal assays and microbiota-perturbation experiments support the routes involved. Selected preparations also thicken, emulsify, retain water and modify food matrices. Yet these findings rarely concern the same material: metabolic, mechanistic and techno-functional studies usually examine different preparations, and retained function is seldom assessed after formulation, processing and digestion. This narrative review uses preparation identity, defined by biological source, processing route and resulting material characteristics, to integrate preparation chemistry, gastrointestinal mechanisms, animal and human outcomes, food-system behavior and food-use considerations. Molecular size, solubility, hydration, binding and fermentability provide a shared physicochemical basis for food-matrix performance and gastrointestinal interactions. Animal doses, human intakes and food-matrix loadings overlap at gram scale, which leaves functional delivery as the unresolved step. Controlled human trials are still few, small and dissimilar in design, so translation remains to be tested. The central question is therefore whether a reproducible EMP preparation can retain its intended function in an acceptable food and produce matched human outcomes. Progress depends on following the same characterized preparation from production and food incorporation through processing, consumption and human evaluation. Full article

Obesity is a major global health concern associated with various metabolic disorders. Fucoidan, a seaweed-derived sulfated polysaccharide, has shown potential in alleviating obesity through modulation of gut microbiota. However, comparative effects of native and depolymerized fucoidan (Dfuc) on HFD-induced obesity and gut microbiota dysbiosis remain unclear. In this study, we compared the anti-obesity effects of fucoidan and Dfuc and evaluated their regulatory effects on gut microbiota and microbial metabolites in HFD-fed mice. Results showed that fucoidan and Dfuc reduced body weight gain, fat accumulation and hepatic lipid abnormalities. They also alleviated liver injury and oxidative stress and inflammation in hepatic and colonic tissues, with Dfuc significantly improving parameters such as serum AST, hepatic MDA, SOD activity, and TNF-α expression compared to the HF group. Furthermore, gut microbiota analysis showed that both fucoidan and Dfuc treatments enriched Alloprevotella and Allobaculum, while fucoidan increased Akkermansia and Blautia, and Dfuc promoted Bifidobacterium and Romboutsia. Moreover, metabolite analysis showed that Dfuc significantly increased fecal acetate and propionate concentrations, and induced more pronounced changes in fecal metabolites related to amino acid, carbohydrate, and bile acid metabolism. These findings suggest that Dfuc holds potential as a functional food ingredient for alleviating HFD-induced obesity and gut microbiota dysbiosis. Full article

Background and Objectives: Modulation of the gut–liver axis with non-viable microbial components is a promising approach to correct metabolic disorders. The aim of the study was to evaluate the short-term efficacy and safety of the postbiotic lysate Lactobacillus rhamnosus DV-NRRL B-68023 on non-invasive measures of hepatic steatosis, transaminase activity, and anthropometric parameters in patients with MASLD. Materials and Methods: In a randomized, double-blind, placebo-controlled trial (NCT06352697), 52 adults were assigned 1:1 to receive the postbiotic Del-Immune V^® Extra (100 mg twice daily; n = 26) or placebo (n = 26) for 3 months followed by a 3-month follow-up without treatment. The registered co-primary endpoints were FLI, HSI, and TyG. Additionally, transaminases, lipid parameters, hs-CRP, and body composition indices were assessed. Results: In the ITT analysis (n = 52), FLI showed a nominal time-by-treatment interaction (p = 0.049), with a between-group difference in change at month 3 of −7.20 points (95% CI: −12.95 to −1.46). HSI and TyG did not differ significantly between groups. In exploratory ITT analyses, waist circumference showed a significant time-by-treatment interaction (p = 0.003), whereas the interaction for visceral fat was not significant (p = 0.079). ALT and AST decreased significantly within the postbiotic group, but the corresponding time-by-treatment interactions were not significant (p = 0.340 and p = 0.111, respectively). Lipid parameters and hs-CRP did not differ significantly between groups. All adverse events were mild and self-limiting. Conclusions: Three months of Lactobacillus rhamnosus lysate DV-NRRL B-68023 was well tolerated. Among the three registered co-primary surrogate indices, only FLI showed a nominal between-group difference; HSI and TyG did not. An exploratory reduction in waist circumference was observed, whereas the ALT and AST changes were not significantly different from placebo. These findings warrant confirmation in larger studies using direct liver assessments and longer follow-up. Full article

Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by hepatic steatosis, metabolic stress, and inflammation. Although free fatty acid (FFA)-based in vitro models are widely used, how OA:PA ratios shape hepatocellular phenotypes remains incompletely characterized. HepG2 cells were treated with oleic acid (OA), palmitic acid (PA), or four OA:PA mixtures (O1P1, O2P1, O3P2, O1P2) for 24 or 48 h. OA and OA:PA mixtures were evaluated at 500 μM total FFA (O2P1: 333.3 μM OA + 166.7 μM PA; O3P2: 300 μM OA + 200 μM PA), whereas PA alone was evaluated at 200 μM. Cell viability, lipid accumulation, ultrastructure, oxidative response, secreted cytokines, and molecular responses were evaluated. Distinct OA:PA ratios generated discrete hepatocellular states rather than a linear steatosis-to-lipotoxicity continuum. O3P2 produced a steatosis-dominant phenotype with pronounced lipid accumulation and relatively limited stress signaling. In contrast, O2P1 combined substantial lipid accumulation with elevated DCF fluorescence, AMP-activated protein kinase (AMPK) phosphorylation, nuclear factor kappa B (NF-κB)-associated inflammatory signaling, and interleukin-8 (IL-8) secretion, representing a pronounced stress-responsive phenotype with selected MASH-relevant features. Selected responses were also evaluated in SNU-449 cells, revealing cell-line-specific patterns. Collectively, these findings support a phenotype-oriented framework for OA:PA ratio selection in hepatocyte-based in vitro MASH modeling. Full article

Chronic hepatitis B virus (HBV) infection remains a leading cause of hepatocellular carcinoma (HCC) worldwide, particularly in Asia. Although nucleos(t)ide analogs suppress viral replication and reduce HCC incidence, residual risk persists, highlighting the need to better understand HBV-driven hepatocarcinogenesis. HBV alters host transcription, DNA repair, lipid metabolism, and the hepatic immune microenvironment. These changes help sustain liver injury, fibrogenesis, and malignant transformation. Ferroptosis, an iron-dependent form of programmed cell death driven by excessive lipid peroxidation, has emerged as an important mechanism in this context, because the liver is central to iron and lipid metabolism. Here, we propose that HBV-driven lipid remodeling shapes ferroptosis susceptibility in a stage-dependent, double-edged manner. During chronic infection, oxidative stress and enrichment of peroxidation-prone lipid substrates may promote ferroptosis-associated hepatocyte injury, immune dysregulation, and fibrosis. After malignant transformation, HBV-related oncogenic programs may instead favor ferroptosis evasion through altered lipid composition and strengthened antioxidant defenses, thereby supporting tumor survival and progression. In this review, we summarize mechanisms linking HBV, lipid metabolic remodeling, and ferroptosis while distinguishing direct HBV-related evidence from findings inferred from other liver disease or cancer models. This HBV-ferroptosis framework may help refine risk stratification and suggest new therapeutic opportunities in HBV-related HCC. Full article

Natural products derived from the Mediterranean diet have attracted considerable interest as potential drug leads owing to their antioxidant and anti-inflammatory properties, as well as their beneficial effects on metabolic disorders such as non-alcoholic fatty liver disease (NAFLD). This study investigated the individual and combined effects of carvacrol, thymol, basil essential oil, and lycopene in an in vitro HepG2 model of hepatic steatosis. Their antioxidant activity was first confirmed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical-scavenging assays. Treatments significantly reduced intracellular lipid accumulation and lipid peroxidation, as demonstrated by Oil Red O staining, LipidSpot™ immunofluorescence, and the TBARS assay. In addition, the natural compounds restored lipid homeostasis by upregulating the β-oxidation- and lipolysis-related markers PPARα, CPT1α, and ATGL, while downregulating PPARγ, a lipogenic regulator, and the pro-inflammatory enzyme 5-lipoxygenase. The combined formulation consistently exhibited the strongest biological activity, showing enhanced efficacy in reducing lipid accumulation, oxidative stress, and oxidative DNA damage, as evidenced by decreased 8-oxo-7,8-dihydroguanine (8-oxo-dG) formation. Overall, these results demonstrate that Mediterranean-diet-derived bioactives, particularly when used in combination, exert multitarget antioxidant activity by reducing oxidative damage, restoring lipid homeostasis, and modulating inflammatory pathways, supporting their potential application in natural product-based strategies for the prevention and management of NAFLD. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a major global metabolic health burden, driving an urgent demand for safe, natural bioactive therapeutics derived from sustainable botanical sources. This study aimed to investigate the therapeutic efficacy and multi-target molecular mechanisms of litchi pericarp oligomeric polyphenols (LPPO) from Litchi chinensis Sonn. cv. Feizixiao against MASLD. A comprehensive multi-tiered pharmacological study design was conducted, integrating computational target prediction (network pharmacology and molecular docking) with in vitro cellular and in vivo animal disease models, combined with multi-omics profiling. Palmitate/oleate (FFA)-induced HepG2 cells and high-fat-diet (HFD)-fed C57BL/6J mice (JAX substrain) were treated with LPPO to evaluate hepatic steatosis, serum lipid profiles, oxidative stress parameters, and fecal lipid excretion. Integrated transcriptomics, metabolomics, network pharmacology, and molecular docking were conducted to pinpoint core bioactive constituents and validate key molecular targets and signaling pathways. LPPO markedly attenuated hepatic lipid accumulation, normalized serum lipid levels (TC, TG, and LDL-C), restored cellular redox balance (SOD and MDA), and promoted systemic lipid clearance via enhanced fecal excretion both in vitro and in vivo. Multi-omics integration identified quercetin as the principal bioactive metabolite driving LPPO-mediated metabolic reprogramming. Mechanistically, LPPO directly bound ALOX5 and downregulated ALOX12B to inhibit arachidonic acid-mediated inflammatory cascades, while suppressing NOS2/DUOX1 and upregulating MPV17L2 to alleviate oxidative/nitrosative stress. Additionally, quercetin downregulated the CD274 (PD-L1) checkpoint axis to reverse hepatic immunosuppression, alongside modulating GMPR, BCKDHA, and IDI1 to rebalance cellular energy allocation and lipid remodeling. LPPO exerts potent multi-target therapeutic effects against MASLD by alleviating lipotoxicity, oxidative stress, and inflammatory cascades. These findings elucidate the molecular basis of LPPO and highlight the potential of litchi pericarp waste as a high-value phytomedicinal resource. Full article

Long-chain polyunsaturated fatty acids (LC-PUFAs), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are essential nutrients for human health, and fish and aquatic products are the primary dietary sources of these bioactive lipids. The endogenous capacity of teleosts to synthesize LC-PUFAs directly determines their nutritional value for human consumers. However, the genetic regulators governing this biosynthetic pathway remain largely unexplored. Here, we show that targeted disruption of dmrt2a, a transcription factor gene, in zebrafish (Danio rerio) via CRISPR/Cas9, alters hepatic LC-PUFA composition and lipid homeostasis. Homozygous dmrt2a^−/− mutants exhibited significantly reduced molar percentages of EPA (C20:5n-3) and DHA (C22:6n-3) in the liver, accompanied by the accumulation of their precursors, C18:2n-6 and C18:3n-3. In addition, the mutants developed a hepatic lipid metabolic disorder characterized by pathological accumulation of lipid droplets and elevated triglyceride levels, thereby providing a novel zebrafish model for research on hepatic steatosis. Transcriptomic profiling revealed that differentially expressed genes between dmrt2a^−/− mutant and wild-type livers were significantly enriched in fatty acid biosynthesis and metabolic pathways. Notably, an LC-PUFA-enriched diet partially rescued the aberrant hepatic lipid phenotype. To our knowledge, this is the first study in any fish species to link a DMRT-family transcription factor to hepatic LC-PUFA composition and lipid homeostasis, suggesting dmrt2a as a potential target for genetic breeding to improve the nutritional quality of aquaculture products. Full article

The periparturient or transition period—roughly three weeks before to three weeks after calving—compresses the most severe metabolic, endocrine and immunological demands of the production cycle into a few weeks and accounts for most clinical disease and involuntary culling in dairy herds. Conventional surveillance relies on downstream indicators—non-esterified fatty acids, β-hydroxybutyrate, calcium and acute-phase proteins—that document failed adaptation without resolving its regulatory origins. Two omics platforms now close that gap. Transcriptomics shows that the liver, adipose tissue, mammary gland, endometrium, rumen epithelium and circulating leukocytes each execute a distinct, temporally ordered program organized around lipid mobilization, gluconeogenesis, endoplasmic reticulum stress, redox defense and inflammatory resolution, layered over a regulatory tier of non-coding RNAs. Metagenomics shows in parallel that rumen, hindgut, uterine, vaginal, teat-apex and colostrum communities are restructured by parturition and by the dietary shift into lactation, with reproducible dysbiotic signatures accompanying ketosis, fatty liver, metritis, endometritis and intramammary infection. Critically, the two layers are mechanistically coupled: microbial short-chain fatty acids, secondary bile acids, purine derivatives and amino acids reprogram hepatic and immune cell transcription, while host lipolysis, inflammation and mineral demand reshape community structure. This review synthesizes both groups of literature within a single framework, formalizes five host–microbiome interfaces supported by paired measurements and identifies the biomarker, nutritional and genetic-selection opportunities that emerge only when host and microbial evidence are read together. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease and is closely associated with obesity, insulin resistance, and the recently conceptualized cardiovascular–kidney–metabolic syndrome. For decades, the pathogenesis of steatosis has been viewed primarily through the lens of insulin and the canonical transcriptional programs it regulates—sterol regulatory element-binding protein 1c, carbohydrate response element-binding protein, peroxisome proliferator-activated receptors, and AMP-activated protein kinase. At the same time, recent data point to the existence of a complex network of non-canonical regulators that, independently of insulin, significantly modulate hepatic lipid metabolism. This review systematizes information on the fibroblast growth factors FGF21 and FGF19, adipokines (adiponectin, leptin), apolipoprotein C-III, as well as the monoamine neurotransmitters serotonin and dopamine. These molecules act within the interorgan axes “liver–adipose tissue,” “gut–liver,” “brain–liver,” and “liver–spleen,” coordinating lipolysis, gluconeogenesis, very-low-density lipoprotein secretion, inflammation, and fibrogenesis. Disruption of the dynamic balance between canonical and non-canonical regulators is central to the progression from simple steatosis to steatohepatitis and fibrosis. The clinical translation of this concept has already begun: the thyroid hormone receptor β agonist resmetirom and the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide have received regulatory approval for specific categories of patients with noncirrhotic metabolic dysfunction-associated steatohepatitis and fibrosis, while FGF21 and FGF19 analogs, the dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 agonist tirzepatide, and agents targeting apolipoprotein C-III are at various stages of clinical development or are being used for related metabolic indications. Expanding the insulin-centric paradigm to include non-canonical axes opens up new diagnostic and therapeutic possibilities for MASLD. Full article

Environmental pollution has emerged as a critical global health threat, with xenobiotic exposure increasingly linked to the pathogenesis of chronic liver diseases. The gut–liver axis has been proposed as a potential mediator in the body’s response to these insults. This review evaluates how selected environmental pollutants—heavy metals, particulate matter (PM), and endocrine-disrupting chemicals (EDCs), particularly Bisphenol A (BPA)—disrupt this homeostatic balance. Evidence indicates that environmental toxins induce gut dysbiosis and impair intestinal barrier integrity. This “leaky gut” phenomenon facilitates the translocation of endotoxins (LPS) into the portal circulation, where they trigger the TLR4/NF-κB signaling pathway in the liver. This leads to the activation of chronic inflammation, oxidative stress, and significant lipid accumulation in the liver. Furthermore, EDCs interfere with hepatic nuclear receptors, directly deregulating lipid metabolism and driving the progression of metabolic dysfunction-associated steatotic liver disease (MASLD). By highlighting the gut–liver axis as a key pathway affected by selected environmental contaminants, this review provides a mechanistic foundation to guide future research toward targeted preventive and therapeutic strategies. Full article