Search Results (3,496)

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

Curcumin, a natural polyphenol derived from turmeric, functions as a potent exogenous antioxidant and exhibits a range of benefits in the prevention and management of metabolic diseases. Despite its extremely low systemic bioavailability, curcumin demonstrates significant bioactivity in vivo, a phenomenon likely attributable to its accumulation in the intestines and subsequent modulation of systemic oxidative stress and inflammation. This article systematically reviews the comprehensive regulatory effects of curcumin on systemic metabolic networks—including glucose metabolism, amino acid metabolism, lipid metabolism, and mitochondrial metabolism—and explores their molecular basis, particularly how curcumin facilitates systemic metabolic improvements by alleviating oxidative stress and interacting with inflammation. Preclinical studies indicate that curcumin accumulates in the intestines, where it remodels the microbiota through prebiotic effects, enhances barrier integrity, and reduces endotoxin influx—all of which are critical drivers of systemic oxidative stress and inflammation. Consequently, curcumin improves insulin resistance, hyperglycemia, and dyslipidemia across multiple organs (liver, muscle, adipose) by activating antioxidant defense systems (e.g., Nrf2), enhancing mitochondrial respiratory function (via PGC-1α/AMPK), and suppressing pro-inflammatory pathways (e.g., NF-κB). Clinical trials have corroborated these effects, demonstrating that curcumin supplementation significantly enhances glycemic control, lipid profiles, adipokine levels, and markers of oxidative stress and inflammation in patients with obesity, type 2 diabetes, and non-alcoholic fatty liver disease. Therefore, curcumin emerges as a promising multi-target therapeutic agent against metabolic diseases through its systemic antioxidant and anti-inflammatory networks. Future research should prioritize addressing its bioavailability limitations and validating its efficacy through large-scale trials to translate this natural antioxidant into a precision medicine strategy for metabolic disorders. Full article

Hepatocellular carcinoma (HCC) is the main type of liver cancer and one of the malignancies with the highest mortality rates worldwide. HCC is associated with diverse etiological factors including alcohol use, viral infections, fatty liver disease, and liver cirrhosis (a major risk factor for HCC). Unfortunately, many patients are diagnosed at advanced stages of the disease and receive palliative treatment only. Therefore, early markers of HCC and novel therapeutic approaches are urgently needed. The endocannabinoid system is involved in various physiological processes such as motor coordination, emotional control, learning and memory, neuronal development, antinociception, and immunological processes. Interestingly, endocannabinoids modulate signaling pathways involved in cell survival, proliferation, apoptosis, autophagy, and immune response. Consistently, several cannabinoids have demonstrated potential antitumor properties in experimental models. The participation of metabotropic and ionotropic cannabinoid receptors in the biological effects of cannabinoids has been extensively described. In addition, cannabinoids interact with other targets, including several ion channels. Notably, several ion channels targeted by cannabinoids are involved in inflammation, proliferation, and apoptosis in liver diseases, including HCC. In this literature review, we describe and discuss both the endocannabinoid system and exogenous phytocannabinoids, such as cannabidiol and Δ⁹-tetrahydrocannabinol, along with their canonical receptors, as well as the cannabidiol-targeted ion channels and their role in liver cancer and its preceding liver diseases. The cannabidiol-ion channel association is an extraordinary opportunity in liver cancer prevention and therapy, with potential implications for several environments that are for the benefit of cancer patients, including sociocultural, public health, and economic systems. Full article

The characteristic green-note aroma of Chinese plum (Prunus salicina) is largely defined by C6 aldehydes and alcohols synthesized through the fatty acid pathway involving lipoxygenase (LOX), hydroperoxide lyase (HPL), and alcohol dehydrogenase (ADH). However, the LOX/HPL/ADH gene families and their potential contributions to C6 volatile formation remain poorly characterized in Chinese plum. Here, we integrated genome-wide identification with cultivar-level volatile profiling and RT–qPCR expression analyses to link candidate genes with C6 volatile accumulation. We identified 8 PsLOX, 3 PsHPL, and 13 PsADH genes and classified them into 2, 1, and 3 subfamilies, respectively. Conserved motifs/domains were shared within each family, whereas gene-structure variation suggested functional divergence; segmental duplication was the main driver of family expansion. To explore their functional relevance to aroma biosynthesis, five major C6 aldehydes and alcohols were analyzed in ten cultivars using solid-phase microextraction/gas chromatography-mass spectrometry (SPME/GC–MS), revealing substantial diversity in green-note composition. Combined with reverse transcription quantitative polymerase chain reaction (qRT–PCR) expression profiling, low PsADH2.7 expression was associated with high hexanal content, whereas elevated PsLOX5 and PsADH2.2 expression corresponded to increased 1-hexanol accumulation. High 2-ethyl-1-hexanol levels were linked to increased PsLOX4.1 and PsHPL1.3 but decreased PsADH1.2 expression. In addition, (Z)-3-hexen-1-ol abundance showed strong positive correlations with PsLOX3.1, PsHPL1.2, and PsADH2.6 expression. This integrated genomic and expression–metabolite analysis highlights candidate genes potentially involved in C6 aldehyde/alcohol biosynthesis underlying the green-note aroma of Chinese plum and provides genetic targets for aroma-oriented breeding. Full article

Microalgae can modify their metabolic pathways as a response to environmental stimuli such as light, temperature, salinity, and nutrient availability, which critically influence the synthesis of lipids and other biomolecules. While extensive studies have focused on the impact of these environmental variables on the accumulation of valuable compounds such as polyunsaturated fatty acids (PUFAs) and triacylglycerols (TAGs), information on the biosynthesis of specialized metabolites, including long-chain hydroxy fatty acids (LCHFAs), long-chain diols (LCDs), and long-chain alkenols (LCAs) is scarce. These metabolites are thought to contribute to the structural integrity of cell walls in certain microalgae, such as Nannochloropsis spp. (Eustigmatophyceae), where they make up a biopolymer known as algaenan. This study investigates how varying light intensities affect the production of LCHFAs, LCDs, and LCAs in Nannochloropsis oceanica over a 12 h light/dark cycle. Our findings provide insights into the lipid biosynthetic pathways in microalgae, revealing that light strongly drives the production of LCHFAs, whereas LCDs and LCAs are less light-dependent and show more variable responses to different light intensities. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease, is a highly prevalent hepatic condition closely linked to metabolic syndrome (MetS). Epigenetic regulators such as microRNAs (miRNAs) have emerged as critical modulators of the molecular pathways underlying MASLD pathogenesis, offering new perspectives for non-invasive diagnosis and targeted therapy. This study aimed to identify and characterize target genes and pathways regulated by two key hepatic miRNAs, namely miR-122 and miR-29a, through a comprehensive in silico bioinformatics approach, to better understand their functional roles in MASLD and MetS. Methods: Target genes of miR-122 and miR-29a were predicted using three databases (TargetScan, DIANA-microT-CDS, and miRWalk), and those identified by at least two databases were selected for downstream analyses. Functional enrichment was performed using Gene Ontology and KEGG pathway analysis. Gene networks and biological process maps were constructed using Metascape, clusterProfiler and Cytoscape. Results: miR-122 was found to negatively regulate genes involved in lipid metabolism, insulin signaling, and inflammatory pathways, including PPARGC1A, PPARA, LPL, TLR4, and HMGCR, contributing to insulin resistance and liver dysfunction. By contrast, miR-29a demonstrated potential hepatoprotective effects by targeting LEP, INSR, IL13, and IL18, enhancing insulin sensitivity and reducing fibrogenic activity. Enrichment analysis revealed strong associations with biological processes, such as STAT phosphorylation, lipid homeostasis, and inflammatory signaling, as well as associations with cellular components, including lipoproteins and plasma membranes. miR-122 and miR-29a exhibit opposing regulatory functions in MASLD pathogenesis. Whereas miR-122 is associated with disease progression, miR-29a acts protectively. These miRNAs may serve as promising biomarkers and therapeutic targets in MASLD and related metabolic conditions. Further validation through experimental and clinical studies is warranted. 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

Endometriosis is a chronic, oestrogen-dependent inflammatory condition affecting approximately 10% of women of reproductive age, frequently associated with chronic pelvic pain, dysmenorrhoea and infertility, substantially impairing quality of life. While pharmacological and surgical therapies represent the standard of care, growing evidence indicates that lifestyle and dietary factors play an important complementary role in symptom management and may influence disease progression. Regular physical activity appears to attenuate systemic inflammation, improve hormonal regulation and support psychological well-being. Dietary patterns rich in anti-inflammatory components, particularly Mediterranean-diets and low-inflammatory diets, have been associated with reduced pain and improved gastrointestinal symptoms, whereas high consumption of red and processed meats may increase disease risk. Micronutrients and selected supplements, including vitamins C, E and D, magnesium, zinc, folate, omega-3 fatty acids, N-acetylcysteine, curcumin, probiotics and green tea polyphenols, show promising but variable evidence for symptom relief. Additional lifestyle factors, such as avoiding endocrine-disrupting chemicals, moderating alcohol intake, ensuring adequate sleep and managing psychological stress, may further modulate inflammatory and hormonal pathways relevant to the disorder. Overall, current evidence indicates that integrating lifestyle interventions alongside conventional treatments offers clinically relevant benefits, although larger, well-designed clinical studies are needed to clarify the magnitude of these effects and to explore further promising lifestyle-based therapeutic approaches. Full article

Background: The transition from the term non-alcoholic fatty liver disease (NAFLD) to steatotic liver disease (SLD), an umbrella term for several related conditions, offers benefits, particularly in identifying cardiometabolic risk factors more effectively. However, the impact of alcohol consumption on liver disease progression remains significant, leading to the recognition of a new entity: MetALD (metabolic dysfunction-associated steatotic liver disease with moderate alcohol intake). Aim: This study aimed to compare characteristics associated with liver disease progression in diabetic patients diagnosed with metabolic dysfunction-associated steatotic liver disease (MASLD) versus those with MetALD. Materials and Methods: In this prospective study, 286 diabetic patients were followed for 12 months. All patients underwent transient elastography (TE) and ultrasound to assess hepatic steatosis. Participants were classified into MASLD and MetALD groups. The performance of fibrosis-4 index (FIB-4), and NAFLD fibrosis score (NFS) were also evaluated. Results: MASLD was diagnosed in 58.2% (167 patients), of whom 4.9% (7 patients) had TE values suggestive for liver cirrhosis. Among those with MetALD, 17.6% (21 patients) had TE values compatible with advanced fibrosis. MASLD subjects presented a slight decrease in liver fibrosis values from 6.58 ± 2.27 kPa to 6.03 ± 1.57 kPa in the 12 months. On the contrary, MetALD subjects had an increase of liver stiffness measurements (LSM) values from 11.83 ± 6.27 kPa to 12.24 ± 8.66 kPa. Conclusions: in diabetic patients, the coexistence of moderate alcohol intake and cardiometabolic risk factors (MetALD) is associated with more advanced liver fibrosis and impaired long-term glycemic control, compared to MASLD alone. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly common and linked to obesity; however, its association with colorectal cancer (CRC) risk in women remains unclear. Materials and Methods: This retrospective cohort study used the Korean National Health Insurance Service health-screening database, including 483,401 women aged 40–59 years examined between 2013 and 2016, followed through 2021. MASLD was defined as hepatic steatosis (hepatic steatosis index ≥ 36 or ICD-10 K76.0) with ≥1 metabolic abnormality and no heavy alcohol use (≥20 g/day). Incident CRC (ICD-10 C18–C20) was analyzed using Cox regression adjusted for demographic, socioeconomic, and metabolic variables. Effect modification was tested across key covariates. Results: MASLD was found in 128,642 participants (26.6%). During a median 7.5-year follow-up, 2432 CRC cases occurred (702 with MASLD). The 7-year cumulative CRC risk was higher in the MASLD group (0.47% vs. 0.43%; p = 0.006). MASLD independently increased CRC risk (adjusted HR 1.10; 95% CI 1.00–1.20). Effect modification was observed for age, dyslipidemia, and waist circumference. MASLD significantly increased CRC risk among women aged 40–49 years (HR 1.26; 95% CI 1.05–1.49), those without dyslipidemia (HR 1.15; 95% CI 1.03–1.28), and with waist < 85 cm (HR 1.15; 95% CI 1.02–1.30). Conclusions: MASLD modestly increases CRC risk in Korean women, particularly among younger, normolipidemic, and non-obese individuals, indicating the need for age- and metabolism-specific risk stratification and suggesting a need for closer clinical attention and metabolic optimization. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) has become highly prevalent worldwide, and its pathogenesis and progression mechanisms remain incompletely understood. An increased activation of innate immune cells in the liver contributes to hepatic fibrogenesis via a chronic loop of inflammation and regeneration processes. Among them are mast cells (MCs), whose role in hepatic cirrhosis secondary to MASLD remains poorly studied. Our aim was to evaluate differences in MC density in cirrhotic liver tissue among patients with MASLD and other chronic liver disease etiologies. For this, a retrospective study of MC count was performed in cirrhotic liver explants obtained from MASLD, alcohol-related liver disease (ALD), and autoimmune hepatitis (AIH). We included a control group of subjects without liver damage. Tryptase-positive MCs were identified by indirect immunofluorescence and quantified as MC density per low-power field (MC/LPF). Group differences were analyzed using the Kruskal–Wallis test with Dunn’s multiple comparisons, considering p < 0.05 as statistically significant. A significantly higher MC density was observed in MASLD, ALD, and AIH patients compared with the control group. The group analysis showed that ALD patients exhibited higher MC density than AIH, with no observed difference between ALD and MASLD. MC density was correlated positively with tobacco smoking and alcohol use in the full analyzed group, suggesting them as risk factors of high MC liver infiltration. We conclude that MC density is augmented in MASLD-related cirrhosis, highlighting potential links between lifestyle factors and MC-mediated hepatic inflammation. Future studies should explore the mechanisms driving this association and evaluate whether targeting MCs could help mitigate fibrosis progression. Full article

Background/Objectives: Non-alcoholic fatty liver disease (NAFLD), also referred to as metabolic dysfunction-associated fatty liver disease (MAFLD), is the most common chronic liver disease, closely associated with obesity and Metabolic Syndrome (MetS). Perilipin-2 (PLIN2), the most abundant lipid droplet protein in the liver, is linked to lipid accumulation and inflammation, the hallmarks of NAFLD. The role of PLIN2 in NAFLD etiopathogenesis remains partially understood. This study aims to elucidate the relationship between serum PLIN2 levels and other disease-related parameters in NAFLD, investigate the role of PLIN2 in disease pathogenesis, and evaluate its utility as a biomarker in NAFLD diagnosis. Methods: The study included 46 patients diagnosed with NAFLD who presented internal medicine outpatient clinics and 44 healthy controls. Results: Serum PLIN2 level was found to be statistically significantly higher in the NAFLD patient group compared to the control group. In the NAFLD group, a statistically significant positive correlation was detected between PLIN2 and Body Mass Index (BMI), hip circumference, C-reactive protein (CRP), and platelet count. In ROC analysis, taking the cut-off value for serum PLIN2 level as 5.52 ng/mL predicted the diagnosis of NAFLD with 50% sensitivity and 97.7% specificity. Conclusions: PLIN2 determination demonstrated high specificity at the proposed cut-off value and may represent a promising complementary biomarker for NAFLD, particularly when interpreted alongside other clinical and laboratory parameters. Circulating PLIN2 appears to be influenced by metabolic and inflammatory parameters. Full article

Lipids are essential biomolecules involved in membrane structure, energy storage, and intracellular signaling. Dysregulation of lipid metabolism (dyslipidemia) plays a central role in a wide spectrum of pediatric metabolic disorders, including both inherited and acquired conditions. Recent and rapid advances in mass spectrometry-based lipidomics have enabled high-resolution profiling of more than one-thousand lipid species, facilitating the discovery of disease-specific lipid signatures that were previously undetectable with conventional biochemical assays. In parallel, the rising prevalence of pediatric obesity, diabetes, asthma, metabolic dysfunction-associated steatotic liver disease (MASLD; formerly referred to as non-alcoholic fatty liver disease or NAFLD) and cancers has accelerated research aimed at uncovering molecular pathways underlying these conditions. Lipidomic approaches have also improved the identification and characterization of rare metabolic disorders. As analytical technologies continue to advance, lipidomics is poised to become a cornerstone of precision medicine in pediatrics, offering new opportunities for early diagnosis, risk stratification, and therapeutic targeting. Full article

Human milk is the benchmark for formulating infant formula, the latter serving as a substitute when breastfeeding is not possible. Nevertheless, the lipid composition and structure of commercially available infant formulas still differ from those of human milk fat. Accordingly, this paper employs a computational–experimental framework to optimize formulations of prepared lipid (PF). The quality of the optimized product was further validated by analyzing volatile organic compounds (VOCs), color, lipid oxidation indicators, and oxidative stability. The results show that a total of 43 fatty acids (FA) were detected in the base oil, and palmitic acid, oleic acid, and linoleic acid are the main types of FA. Through computer simulation, 6 of PF were obtained, which are superior to commercial products (SP) in the similarity score of the parsimonious model, and PF1 has the highest score (84.15). Multivariate statistical analysis indicates that PF may be more suitable for use in infant formula milk powder due to its lipid composition. Gas chromatography-ion mobility spectrometry was used to study the VOCs content of PF and SP, and a total of 35 VOCs were identified. It was found that alcohols and ketones accounted for the highest proportion in PF, while Nitriles, Aldehydes, and Esters were the most abundant in SP. In the comparison of the basic physical and chemical indices between PF and SP, the peroxide value and p-anisidine value of PF are lower, and the overall oxidation stability is stronger than that of SP. This study provides a reference for the preparation and multi-dimensional evaluation of human milk fat substitutes. Full article