Search Results (951)

Non-alcoholic fatty liver disease (NAFLD) is a major metabolic disorder characterized by hepatic lipid accumulation, oxidative stress, and disturbance of lysosomal degradation. Central to these processes is glutathione (GSH), a key antioxidant regulating redox balance and cellular homeostasis. This study aimed to evaluate the therapeutic potential of two dietary antioxidants—astaxanthin and Garcinia indica (kokum)—in modulating hepatic redox status, lysosomal function, and metabolic gene expression in a murine model of diet-induced NAFLD. A total of 120 male Swiss Webster mice were allocated into control and steatotic groups, followed by a 90-day supplementation period with astaxanthin, kokum, or their combination. Liver tissue was collected post-supplementation for biochemical, antioxidant, and qRT-PCR analyses. Outcomes included lysosomal enzymes activities, superoxide dismutase (SOD), GSH, vitamin C, total polyphenols, DPPH radical-scavenging activity, and total antioxidant capacity (TAC). NAFLD induced marked oxidative stress, lysosomal overactivation, and alteration of antioxidant-related gene expression. Combined supplementation restored GSH, enhanced TAC, reduced lysosomal stress markers, and significantly upregulated nuclear factor erythroid 2-related factor 2 (Nfe2l2) while downregulating fatty acid synthase (FASN) and partially rescuing lipoprotein lipase (LpL). Correlation analyses revealed strong associations between antioxidant capacity, lysosomal function, and transcriptional regulation, supporting the therapeutic relevance of combined antioxidant therapy for concurrent redox and lysosomal dysregulation in NAFLD. These findings underscore the therapeutic potential of targeting redox and cellular degradation pathways with antioxidant-based interventions to re-establish hepatic metabolic balance in NAFLD and related disorders. Full article

Long-term excessive fat intake can easily induce metabolic diseases such as fatty liver and hyperlipidemia. As a natural active ingredient, polysaccharides exhibit notable lipid-lowering effects and can serve as effective lipid regulators. Nevertheless, the lipid-lowering effect of Arabica coffee cherry peel polysaccharides (CCPPs) and the underlying regulatory mechanism remain poorly understood. This study isolated polysaccharides from coffee cherry peel, and their functional properties and the lipid-lowering effects and mechanisms on hyperlipidemic mice. In high-fat diet-fed (HFD-fed) mice, CCPP administration had significant regulatory effects on various metabolic parameters. In laboratory mice where hyperlipidemia is induced by a high-fat diet, CCPP administration improved serum lipid levels and demonstrated anti-inflammatory and antioxidant effects. These benefits were achieved by reducing pro-inflammatory cytokine expression, enhancing antioxidant enzyme activity, and lowering overall oxidative stress. Additionally, it effectively decreased fat area in liver tissues and adipocytes. Specifically, compared with the control group, after high-dose CCPP intervention, the adipocyte area of mice on a high-fat diet was significantly reduced by 41.3%. Notably, CCPP intervention resulted in a shift in the gut microbiota composition. At the phylum level, the model group showed a significant increase in Bacillota and a concomitant reduction in Bacteroidetes in comparison with the control group. Compared with the model group, CCPP intervention, especially in the CCPP-H group, resulted in an increase in the proportion of Bacteroidetes and a decrease in Bacillota. At the genus level, CCPP modulated the abundances of key bacterial genera; for instance, the relative abundance of Lachnospiraceae_NK4A136_group increased from 2.64% in the model group to 11.9% in CCPP-H group, while Faecalibaculum decreased from 62.69% to 41.27% in CCPP-L group and 25.29% in CCPP-H group. These shifts suggest that CCPP has a reparative effect on the gut microbial composition, potentially contributing to the promotion of gut health. Taken together, these factors highlight the promise of CCPP as a functional food ingredient for dietary interventions to ameliorate obesity and hyperlipidemia. Full article

Hepatic ischemia–reperfusion injury (IRI) is a critical clinical condition associated with liver transplantation and acute liver injury. This study investigated the role of sulfide quinone oxidoreductase (SQOR) and its downstream product, supersulfides, in hepatic IRI. C57BL/6NJ mice were subjected to 45 min of partial hepatic ischemia, followed by reperfusion lasting 4 h. Control of shRNA mediated knockdown of SQOR expressing adeno-associated viral vectors were administered 3 weeks prior to liver ischemia. In the shRNA-mediated knockdown of SQOR group, the hydro-trisulfide donor sodium trisulfide was administered daily for 1 week prior to the induction of liver ischemia. SQOR played a crucial protective role during hepatic IRI by facilitating electron transport to the mitochondrial respiratory chain and maintaining the oxidized and reduced nicotinamide adenine dinucleotide ratio. Administration of sodium trisulfide, exhibited protective effects against hepatic IRI. Sodium trisulfide restored the oxidized and reduced nicotinamide adenine dinucleotide ratio, reduced oxidative stress, and preserved the expression of key enzymes involved in the sulfide oxidation pathway. SQOR and supersulfides contribute to hepatic protection against IRI, likely through their potent antioxidative and redox-regulating functions, and highlight sodium trisulfide as a potential therapeutic agent. Full article

Infantile-onset lysosomal acid lipase deficiency (LAL-D) (Wolman disease, historically) is a rare inherited, rapidly progressive disorder caused by pathogenic variants in the LIPA gene, which encodes the enzyme LAL. LAL is essential for the metabolism of cholesteryl esters and triglycerides. LAL deficiency leads to the accumulation of cholesteryl esters and triglycerides within the lysosomes, macrophages, and parenchymal cells in most tissue types, including those in the liver, gastrointestinal tract, and lymph nodes but excluding the central nervous system. Infants with rapidly progressive LAL-D present with gastrointestinal disturbance, adrenomegaly with calcification, hepatosplenomegaly, growth failure due to malabsorption, and systemic inflammation. If untreated, rapidly progressive LAL-D typically leads to death within the first year of life. Treatment takes the two-pronged approach of sebelipase alfa, a human lysosomal acid lipase enzyme replacement therapy (ERT) that improves lipid metabolism, combined with nutritional management. Dietary substrate (lipid) reduction, known as substrate reduction therapy, is essential for optimal management in LAL-D. Following a nutritional plan and managing gastrointestinal disturbances together reduce systemic inflammation and improve growth, gut function, liver health, quality of life, and survival in patients with infantile-onset LAL-D. A multidisciplinary specialized team is necessary to manage the highly complex, multisystemic conditions in these patients. Nutritional management of LAL-D has evolved with increasing experience with the clinical management of ERT-treated infantile-onset LAL-D. A review of guidance for best practice nutritional management is needed. This narrative review aims to provide updated recommendations and guidance for the optimal nutritional management of infantile-onset LAL-D. Full article

The liver is the central organ in metabolism; however, modeling hepatic diseases remains limited by current experimental models. Animal models frequently fail to predict human liver physiology, while primary hepatocytes rapidly dedifferentiate in culture. We performed comprehensive transcriptomic profiling of induced pluripotent stem cells (iPSCs) differentiation into hepatocyte-like cells (HLCs) under two-dimensional (2D) and three-dimensional (3D) culture conditions. RNA sequencing analysis revealed the sequential activation of lineage-specific markers across major developmental stages: definitive endoderm (FOXA2, SOX17, CXCR4, CER1, GATA4), posterior foregut (PROX1, GATA6), and hepatoblasts (HNF4A, AFP). Comparative analysis demonstrated a markedly enhanced hepatic gene expression of 3D organoids, as demonstrated by a 33-fold increase in HNF4A expression and elevated levels of mature hepatocyte markers, including ALB, SERPINA1, and UGT2B15. However, the 3D cultures retained fetal characteristics (290-fold higher AFP expression) and exhibited significantly impaired metabolic function, with CYP3A4 expression levels reduced by 2000-fold compared to the adult human liver. This partial maturation was further supported by a moderate correlation with adult liver tissue (ρ = 0.57). We demonstrated high reproducibility across five biologically distinct iPSCs lines, including those derived from patients with rare monogenic disorders. The establishment of quantitative benchmarks provides a crucial tool for standardizing in vitro liver models. Furthermore, we delineate the specific limitations of the current model, highlighting the need for further protocol optimization to enhance metabolic maturation and P450 enzyme activity. Functional validation of metabolic activity (CYP enzyme assays, albumin secretion) was not performed; therefore, conclusions regarding hepatocyte functionality are based on transcriptomic evidence. Full article

Obesity and metabolic disorders are an increasing concern in companion animals, creating demand for herb-derived nutraceuticals and functional feeds. This study evaluated whether a water extract of Aster pekinensis (AP) ameliorates high-fat-diet (HFD)-induced obesity and metabolic dysfunction in mice. The phytochemical profile of AP was characterized by mass spectrometry, revealing oleanane-type triterpenoid saponins and dicaffeoylquinic acids. Male C57BL/6 mice were fed an HFD and orally given AP (10–200 mg/kg/day) for 12 weeks, with normal diet and untreated HFD groups as controls. AP at 50–200 mg/kg/day reduced body-weight gain, adipose tissue mass and food efficiency without lowering food intake, and improved fasting glucose and atherogenic lipid indices. AP also enhanced glucose tolerance and insulin sensitivity, attenuated hepatic steatosis, hepatocellular ballooning, lobular inflammation and non-alcoholic fatty liver disease (NAFLD) Activity Score, and decreased serum liver enzyme activities. These effects were accompanied by modulation of hepatic genes involved in lipogenesis and inflammation. Together, these findings indicate that AP extract mitigates diet-induced obesity and NAFLD-like liver injury and supports further development as a herb-derived nutraceutical or functional feed ingredient for managing obesity-related metabolic disorders in companion animals. Full article

Microalgae are sustainable sources of bioactive compounds with broad hepato-protective potential. This review synthesizes evidence for five major classes—carotenoids such as astaxanthin and fucoxanthin, polysaccharides such as paramylon and fucoidan, phycobiliproteins such as phycocyanin, omega-3 fatty acids, and phenolic extracts—linking their actions to key liver injury mechanisms. Preclinically, these compounds enhance antioxidant defenses, improve mitochondrial function, suppress inflammatory signaling, regulate lipid metabolism, modulate the gut–liver axis, and inhibit hepatic stellate cell activation, thereby attenuating fibrosis. Consistent benefits are observed in models of non-alcoholic and alcoholic fatty liver disease, drug-induced injury, ischemia–reperfusion, and fibrosis, with marked improvements in liver enzymes, oxidative stress, inflammation, steatosis, and collagen deposition. Emerging evidence also highlights their roles in regulating endoplasmic reticulum stress and ferroptosis. Despite their promise, translational challenges include compositional variability, a lack of standardized quality control, limited safety data, and few rigorous human trials. To address these challenges, we propose a framework integrating multi-omics and AI-assisted strain selection with specification-driven quality control and formulation-aware designs—such as lipid carriers for carotenoids or rational combinations like fucoxanthin with low-molecular-weight fucoidan. Future priorities include composition-defined randomized controlled trials in non-alcoholic fatty liver disease, alcoholic liver disease, and drug-induced liver injury; harmonized material specifications; and multi-constituent interventions that synergistically target oxidative, inflammatory, metabolic, and fibrotic pathways. Full article

Probiotics hold great potential in aquaculture, as they can effectively modulate gut microbiota and improve fish health, thereby enhancing farming efficiency. Translating this potential into practical application critically relies on screening high-efficacy probiotic strains. This study evaluated the growth-promoting and health-enhancing effects of probiotic candidates Lactobacillus rhamnosus GG (LGG), Lactobacillus plantarum FZU310 (LP-FZU310) and Bacillus subtilis FZU103 (BS-FZU103) in largemouth bass (Micropterus salmoides). After feeding different probiotics for 30 days, the growth, antioxidant, and intestinal enzyme indicators of M. salmoides were detected. BS-FZU103 demonstrated superior efficacy among the tested strains, showing significant differences in both specific growth rate (SGR) (p < 0.05) and condition factor (CF) (p < 0.05). It also markedly enhanced hepatic antioxidant status, elevating superoxide dismutase and glutathione peroxidase activities while reducing malondialdehyde levels by 80%. Improved liver integrity was indicated by significant decreases in serum alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase. Digestively, BS-FZU103 specifically increased intestinal amylase activity by 14.7%, without affecting protease or lipase, suggesting enhanced carbohydrate digestion. 16S rRNA sequencing revealed BS-FZU103 remodeled gut microbiota, increasing Proteobacteria abundance at the phylum level and enriching Bacillus while reducing Clostridium sensu stricto 1 at the genus level. Functional prediction based on PICRUSt2 indicated an enhanced metabolic potential of the gut microbiota, with inferred upregulation of pathways related to carbohydrate transport and metabolism (e.g., ABC transporters) and intestinal enzymatic activities. Collectively, BS-FZU103 is associated with metabolic modulation, promoting M. salmoides growth through gut microbiota remodeling, hepatic antioxidant fortification, and targeted augmentation of carbohydrate utilization efficiency. Full article

This study was conducted to evaluate the effects of chia seed oil (CSO; Salvia hispanica L.) on the growth performance, haematological-biochemical parameters, immune-related gene expression, and disease resistance to Aeromonas hydrophila in common carp (Cyprinus carpio). The fish were fed diets containing 0%, 0.5%, 1%, and 2% CSO for 60 days. The results showed a significant improvement in final weight, specific growth rate (SGR), and feed conversion ratio (FCR) in fish fed diets containing 1% and 2% CSO compared to the control group. Haematocrit (Hct) and haemoglobin (Hb) levels increased in the CSO groups, while serum triglyceride and cholesterol levels decreased significantly, particularly in the 1% CSO group. The observed decrease in liver enzyme activities (AST, ALT) suggested a hepatoprotective effect of CSO. In the stress test with A. hydrophila, the highest survival rate (80%) was recorded in the 2% CSO group. Furthermore, gene expression analyses performed on spleen tissue revealed an increase in the expression of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-8 in the groups fed with CSO, particularly at the 1% level. These findings indicate that adding 1–2% CSO to carp feed promotes growth, improves lipid metabolism, strengthens immune status, and increases resistance to bacterial infection. Consequently, the use of CSO as a sustainable and functional additive to fish oil in fish feed is suggested. Full article

Background/Objectives: Alcohol Use Disorder (AUD) and Substance Use Disorders (SUDs) can affect both the liver, where clotting factors are synthesized, and the coagulation system, which prevents acute bleeding. Methods: This study included 451 inpatients undergoing addiction detoxification and 150 healthy controls. Patients were stratified by substance type: Alcohol (n = 110), Cannabinoid (n = 71), Methamphetamine (n = 110), Multiple-Substance (Methamphetamine + Cannabinoid, n = 110), and Opioid (n = 50) users. Age-matched control groups (mean ages 45, n = 50; 30, n = 100) were used. Serum levels of Ca, INR, PT, APTT, PLT, AST, and ALT, alongside sociodemographic variables, were assessed. Results: Significant group differences were observed in ALT, AST, PT, APTT, and PLT (p < 0.001). Notably, PT was lower in Multiple Substance and Methamphetamine users; APTT was elevated in Cannabinoid users; AST was higher in Alcohol users; and Methamphetamine and Opioid users exhibited both decreased AST and ALT. Post hoc analyses confirmed substance-specific effects (p < 0.001). Regular cigarette use was significantly more prevalent among alcohol and substance user groups compared to controls; however, smoking did not exert a significant effect on the evaluated biochemical or coagulation parameters. Conclusions: These findings demonstrate that liver enzymes and coagulation parameters can vary significantly by substance type. Observed alterations in AST, ALT, PT, APTT, and PLT suggest that substance use may exert substance-specific effects on hepatic and haemostatic function, highlighting potential risks for bleeding or thrombotic complications. Monitoring these parameters in AUD and SUD patients could provide valuable clinical insights, allowing for more tailored and proactive management strategies. While the underlying mechanisms remain to be fully elucidated, these results emphasize the importance of considering substance-specific physiological impacts when assessing liver and coagulation health in addicted populations. Full article

Backgrounds: While the conditionally essential amino acid taurine is known to confer hepatoprotection against injury through anti-inflammatory and antioxidant mechanisms, it remains unclear whether it plays an active role in the process of hepatocarcinogenesis. Emerging research portrays taurine as a double-edged sword in oncology, with its capacity to either inhibit or facilitate carcinogenesis being contingent upon the specific tumor microenvironment. Objectives: Investigating the effect of taurine on hepatocellular carcinoma progression and its underlying mechanisms. Methods: A hydrodynamic tail vein injection (HDT) model of primary hepatocellular carcinoma was established in mice to validate the effects of taurine and its downstream bile acid synthesis pathway on liver cancer progression. Subsequent RNA sequencing analysis was performed to investigate the molecular pathways through which taurine exerts its functions. Results: Supplementation of taurine or overexpression of its transporter SLC6A6 significantly accelerated HCC development in vivo. Inhibition of taurine transporter abrogated the tumor-promoting effects of the bile acid synthesis enzymes CYP7A1 and BAAT. This suppression may be mediated through the blockade of the cell cycle, p53 signaling pathway and metabolic pathways. Conclusions: Our findings demonstrate that taurine plays a vital role in the tumor-promoting activities of HCC. Full article

Background: Liver transplantation is a life-saving procedure for patients with end-stage liver disease, yet the immunological consequences of surgical trauma in these patients are not fully understood. The liver plays a central role in immune regulation, and its dysfunction in HBV-related chronic liver disease may alter the systemic stress response to surgery. Aim: This study aims to evaluate the stress response to surgical trauma of patients undergoing living donor liver transplantation (LDLT) for HBV-related chronic liver disease in comparison to living liver donors (LLDs). Methods: This prospective study included 20 LDLT recipients with HBV infection and 20 LLDs who underwent living donor hepatectomy between August 2020 and February 2021. Specific biochemical markers (IL-1, IL-4, IL-6, IL-22, IFN-γ, TNF-α, TGF-β, GM-CSF, GLDH, and GalactB) were measured at designated intervals: preoperative day 0 (Preop), immediately after incision (Incision), post-hepatectomy (Hepatectomy), postoperative day 0 (POD0), POD1, and POD3 using enzyme-linked immunosorbent assay (ELISA). Routine hematological and biochemical parameters (WBC, HGB, PLT, RDW, MPV, PDW, AST, ALT, ALP, GGT, albumin, total bilirubin, plateletcrit, phosphorus, fibrinogen, and INR) were measured regularly at five predetermined times: Preop, POD0, POD1, POD2, and POD3. Results: Prior to LDLT, LDLT recipients had significantly lower levels of pro-inflammatory cytokines (IL-1, IL-6, TNF-α, IFN-γ) compared to LLDs (p < 0.05). However, following liver implantation, these cytokine levels increased significantly at POD0, POD1, and POD3 (p < 0.001). Specifically, IL-1 levels elevated from 0 in the preop period to 21.5 (97.5) in POD3, and IL-6 elevated from 0 in the preop period to 28.3 at POD3 (p = 0.056). Similarly, TNF-α and IFN-γ levels exhibited significant upward trends (p < 0.05). In contrast, cytokine levels in LLDs remained stable throughout the perioperative period, revealing no statistically significant variations (p > 0.05). Routine hematological and biochemical parameters demonstrated significant postoperative fluctuations in LDLT recipients, reflecting the metabolic and immune restoration process. Conclusions: These findings indicate that patients with HBV-related chronic liver disease exhibit a diminished stress response to trauma due to underlying immune dysregulation caused by chronic hepatic dysfunction. However, after LDLT, the stress response gradually normalizes, suggesting that liver transplantation not only restores hepatic function but also reestablishes immune homeostasis, potentially reducing infection risks and improving postoperative recovery. These findings emphasize the crucial role of the liver in regulating the body’s stress response to trauma and highlight the immunological benefits of LDLT in restoring immune homeostasis. Full article

Background/Objective: Diabetic nephropathy (DN), a key microvascular complication of type 2 diabetes (T2DM), drives significant morbidity, mortality, and healthcare costs. Vitamin D deficiency has been linked to renal dysfunction, but its role in DN remains unclear. This study assessed the association between vitamin D status and DN versus T2DM without nephropathy. Methods: This cross-sectional hospital-based study included 399 participants (299 DN, 100 T2DM without nephropathy) at a tertiary endocrine clinic. Demographic, clinical, and biochemical data, including serum 25(OH)D, were collected. Chi-square and Mann–Whitney compared categorical and continuous variables, respectively, and multinomial logistic regression assessed the association between vitamin D status and DN (p < 0.05). Results: Patients with DN were older (58.2 ± 7.95 vs. 51.4 ± 9.94 years, p < 0.001), had more advanced CKD (stages 2–3b: 84.6% vs. 20.0%, p < 0.001), and higher albuminuria (moderate: 80.3% vs. 19.0%; severe: 18.4% vs. 0%, p < 0.001). They also showed poorer glycemic control, elevated urea and creatinine, lower serum albumin, dyslipidemia, elevated liver enzymes, and higher uric acid (all p < 0.05). Vitamin D deficiency was more prevalent in DN (37.7% vs. 8.0%, p < 0.001). Unadjusted multinomial regression indicated that T2DM patients without nephropathy had a 91% lower risk of vitamin D deficiency (RRR 0.09; 95% CI 0.04–0.19, p < 0.001) and an 87% lower risk of insufficiency (RRR 0.13; 95% CI 0.05–0.26, p < 0.001) compared with DN patients. After adjusting for age, HbA1c, creatinine, duration of diabetes and eGFR, the reduced risk of deficiency remained significant (RRR 0.04; 95% CI 0.01–0.16, p < 0.001), while the association with insufficiency was no longer significant (p = 0.310). Conclusions: This study shows a significant association between vitamin D deficiency and diabetic nephropathy, though its cross-sectional design precludes causal inference. Reverse causality and residual confounding cannot be excluded. Patients with DN had poorer glycemic control, dyslipidemia, and renal function, along with more frequent vitamin D deficiency. Routine vitamin D monitoring may support early detection and risk stratification in T2DM. Full article

Canine epilepsy often resists conventional antiepileptic drugs (AEDs), which affects their quality of life. Cannabidiol (CBD) has anticonvulsant properties; however, evidence of its use in canine epilepsy is limited and contradictory. This prospective pilot study aimed to investigate the potential advantages, safety profile, and effects of CBD on quality of life when used as an adjunctive therapy in cases of drug-resistant epilepsy in canines. Thirteen dogs with refractory epilepsy, all on 2–6 concurrent AEDs, were enrolled. A single-arm pretest–post-test design was used. CBD was titrated from 0.5 mg/kg BID 2.5 mg/kg q12h. The primary outcome was the change in seizure frequency. Secondary outcomes included changes in seizure severity, seizure cluster, hematological and biochemical parameters, and owner-reported quality of life (QoL). Significant overall seizure frequency reduction (p = 0.02) with the median decreased from 11 (IQR 9–22) during the pre-intervention period to 5 (IQR 2–13) at the post-intervention follow-up. Notably, 61.5% of the dogs achieved a ≥50% reduction in seizure frequency. The number of seizure clusters was significantly decreased (p = 0.001). Most hematological/renal parameters remained stable; however, Alkaline Phosphatase (ALP) levels significantly increased (p < 0.001). The owners reported positive CBD perceptions and an improved quality of life. CBD shows the potential for refractory canine epilepsy, especially in clusters. Increased hepatic enzyme levels necessitate rigorous monitoring, particularly with the concurrent use of AEDs. This groundbreaking study explored the application of CBD in managing canine epilepsy, utilizing a “start-low, go-slow” strategy to minimize adverse effects while effectively controlling seizures. Our findings underscore the necessity of customizing CBD dosages for individual needs and highlight the critical importance of monitoring liver function. This study challenged the traditional one-size-fits-all dosing approach. It provides the first evidence and practical framework for the use of CBD to treat canine epilepsy in Asia, detailing the pioneering approach and the initial findings from this cohort. Full article

The prevalence of chronic diseases, including obesity and related endocrine disorders, has risen significantly in recent decades. As a result, there has been growing interest in fermented foods with probiotic properties, such as kefir, which have potential health benefits. This study aimed to evaluate the hepatoprotective and antioxidant effects of kefir milk (KM) in a high-fat diet (HFD)-induced obesity rat model, complemented by in silico molecular docking studies with antioxidant enzymes. Twenty-four adult rats were divided into four groups: control (1 mL/100 g bw semi-skimmed cow milk), KM (1 mL/100 g bw kefir milk), HFD (1 mL/100 g bw semi-skimmed cow milk + high-fat diet), and KM/HFD (1 mL/100 g bw kefir milk + high-fat diet). After 60 days of treatment, biochemical assays and histological examinations were performed to assess the effects on lipid profiles and organ health. Kefir milk demonstrated significant antioxidant activity, with increased total phenolic content and enhanced DPPH, ABTS, and FRAP radical scavenging activities compared to commercial milk. Furthermore, KM administration protected against liver metabolic disruptions (ALT, AST, and LDH) induced by the high-fat diet and reduced lipid peroxidation in liver and testis tissues. KM supplementation also increased the activity of key antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Additionally, KM improved the fatty acid composition and decreased the de novo lipogenesis (DNL) index, as well as enzyme activities (SCD and Elovl6) associated with the high-fat diet. Histological analysis of liver, pancreas, and heart tissues revealed that kefir milk attenuated structural damage caused by the high-fat diet, suggesting its protective role in oxidative stress regulation and organ function. These findings underscore the potential of kefir milk as a functional food for preventing metabolic disturbances and liver damage associated with obesity. Full article