Search Results (2,348)

The endocannabinoid system (ECS), composed of receptors, endocannabinoids, and enzymes that regulate biosynthesis and degradation, plays a fundamental role in the physiology and pathology of the gastrointestinal tract, particularly in the small and large intestine and liver. Specifically, cannabinoid receptor type 1 (CB1R) and cannabinoid receptor type 2 (CB2R), located principally in the nervous system and immune cells, orchestrate processes such as intestinal motility, intestinal and hepatic inflammation, and energy metabolism, respectively. The main endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), influence appetite, body weight regulation, and inflammatory states and thus have implications in obesity, non-alcoholic fatty liver disease (NAFLD) and irritable bowel syndrome (IBS). Recent studies have highlighted the therapeutic potential of targeting the ECS to modulate gastrointestinal and metabolic diseases. In particular, peripheral CB1R antagonists and CB2R agonists have shown efficacy in treating intestinal inflammation, reducing hepatic steatosis, and controlling IBS symptoms. Moreover, the ECS is emerging as a potential target for the treatment of colorectal cancer, acting on cell proliferation and apoptosis. This review highlights the opportunity to exploit the endocannabinoid system in the search for innovative therapeutic strategies, emphasizing the importance of a targeted approach to optimize treatment efficacy and minimize side effects. Full article

In this work, the hypolipidemic and antioxidative capacity of FSGLR (S7) and GIEWA (S10) from miiuy croaker swim bladders was explored systematically in an oleic acid (OA)-induced nonalcoholic fatty liver disease (NAFLD) model of HepG2 cells. Moreover, the hypolipidemic activity of S7 and S10 and their antioxidative abilities were preliminarily investigated in combination with molecular docking technology. The results indicated that S7 and S10 could decrease the amount of lipid accumulation and the content of triglycerides (TG) and total cholesterol (TC) in the OA-induced NAFLD cell model in a dose-dependent manner. In addition, S7 and S10 exhibited better bile salt binding, pancreatic lipase (PL) inhibition, and cholesterol esterase (CE) inhibition capacities. The hypolipidemic mechanisms of S7 and S10 were connected with the downregulation of the mRNA expression levels of adipogenic factors, including sterol-regulatory element-binding protein-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), sterol-regulatory element-binding protein (SREBP)-2, hydroxymethylglutaryl-CoA reductase (HMGR), and fatty acid synthase (FAS) (p < 0.01), and the upregulation of the mRNA expression of β-oxidation-related factors, including carnitine palmitoyltransferase 1 (CPT-1), acyl-CoA oxidase 1 (ACOX-1), and peroxisome proliferator-activated receptor α (PPARα). Moreover, FSGLR (S7) and GIEWA (S10) could significantly protect HepG2 cells against OA-induced oxidative damage, and their antioxidant mechanisms were related to the increased activity of intracellular antioxidant proteases (superoxide dismutase, SOD; glutathione peroxidase, GSH-PX; catalase, CAT) to remove excess reactive oxygen species (ROS) and decrease the production of malondialdehyde (MDA). The presented findings indicate that the hypolipidemic and antioxidant functions and mechanisms of S7 and S10 could make them potential hypolipidemic and antioxidant candidates for the treatment of NAFLD. Full article

Objectives: Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic disorder of the liver and affects many people worldwide. Intestinal bacteria are thought to be involved in the pathological progression of NAFLD; therefore, improving the intestinal microbiota may be important in controlling NAFLD. In this study, we assessed the effects of water-soluble cellulose acetate (WSCA) on the intestinal microbiota in a non-alcoholic steatohepatitis (NASH) mouse model. Methods: NASH model (STAM mice) was created by streptozotocin injection and feeding the mice a high-fat diet. The serum biochemical parameters were analyzed. Intestinal bacterial populations were analyzed using paired-end sequencing of 16S rRNA, 18S rRNA, and internal transcribed spacer gene. Results: Our findings indicated that WSCA administration tends to improve the serum alanine aminotransferase and glucose levels in STAM mice and decreased the alpha diversity and altered the beta diversity of their intestinal microbiota. Additionally, WSCA intake resulted in an increase in the abundance of Coriobacteriaceae_UCG-002 and a decrease in the abundance of Enterobacter. Conclusions: WSCA intake can alter specific microbial compositions to improve blood glucose levels and liver functions and may improve the pathogenesis of NAFLD. Full article

Non-alcoholic fatty liver disease (NAFLD) in the pediatric population has emerged as a significant health concern due to its alarming rise in prevalence. In children, the characteristics of the disease differ from those seen in adults. NAFLD may progress to more severe liver disease in children compared to adults with similar profiles. Liver biopsy remains the gold standard for diagnosis; its invasive nature and high cost limit its use as a first-line tool. Alternatively, magnetic resonance imaging (MRI) techniques, such as magnetic resonance imaging-estimated liver proton density fat fraction (MRI-PDFF), have shown a good correlation with the degree of histological steatosis, although their use is limited by high costs and limited accessibility. Controlled attenuation parameter (CAP), integrated with vibration-controlled transient elastography (VCTE) (FibroScan^®), is a novel non-invasive, accessible, and effective method for diagnosing hepatic steatosis. In this article, we reviewed the existing literature on the diagnostic accuracy of CAP in pediatric NAFLD. The PubMed and EMBASE databases were searched. Seven relevant studies were identified, conducted in pediatric hospital populations with specific demographic characteristics. Two of these studies compared CAP with liver biopsy, one compared CAP with liver biopsy and MRI-PDFF, and the remaining four compared CAP with MRI. Overall, CAP proved to be accurate in detecting the presence or absence of fatty infiltration, positioning it as a promising tool to simplify the diagnosis of NAFLD in children. However, further studies in larger populations are needed to confirm these findings and facilitate its implementation in routine clinical practice. Full article

Chronic kidney disease (CKD) is now the world’s top seventh cause of death from a non-communicable disease, and its incidence is projected to increase further as its major risk factors, including obesity, diabetes, hypertension, and non-alcoholic fatty liver disease (NAFLD), continue to rise. Current evidence has linked the increased prevalence of CKD, diabetes, hypertension, and NAFLD to chronic exposure to the metal pollutant cadmium (Cd). Exposure to Cd is widespread because diet is the main exposure route for most people. Notably, however, the health risk of dietary Cd exposure is underappreciated, and the existing tolerable exposure guidelines for Cd do not afford health protection. New health-protective exposure guidelines are needed. From one’s diet, Cd is absorbed by the intestinal epithelium from where it passes through the liver and accumulates within the kidney tubular epithelial cells. Here, it is bound to metallothionine (MT), and as it is gradually released, it induces tubular damage, tubulointerstitial inflammation and fibrosis, and nephron destruction. The present review provides an update on our knowledge of the exposure levels of Cd that are found to be associated with CKD, NAFLD, and mortality from cardiovascular disease. It discusses the co-existence of hypertension and CKD in people environmentally exposed to Cd. It highlights nuclear and mitochondrial targeting and zinc deficiency as the universal cytotoxic mechanisms of Cd. Special emphasis is placed on the novel antioxidative function of zinc involving de novo heme biosynthesis and the induced expression of heme oxygenase-1 (HO-1). Other exogenous biomolecules with promising anti-Cd toxicity are highlighted. Full article

Objective: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic condition affecting a broad population. This review aimed to identify and summarize the current evidence on bioactive-substance-based interventions for adults with MASLD, formerly known as nonalcoholic fatty liver disease (NAFLD), covering publications from 2000 to 2023. Methods: A search was conducted across six databases (MEDLINE, CINAHL, Cochrane CENTRAL, Cochrane Database of Systematic Reviews, Food Science Source, and SPORTDiscus) for randomized controlled trials and other study types (e.g., prospective cohort studies and systematic reviews), reflecting the scoping nature of this review. The search was limited to studies in adults (>18 years old), with an intervention of interest and at least one comparator group. Results: A total of 4572 articles were retrieved, with 201 full-text articles screened for eligibility. Of these, 131 primary studies and 49 systematic reviews were included in the scoping review. The most studied bioactive substances were Curcumin (Turmeric) (n = 25), Silymarin (Milk Thistle) (n = 17), Resveratrol (n = 10), Coffee (n = 7), Green Tea (n = 5), and Berberine (n = 5 each). Moreover, 46 studies reported on 36 other bioactive substances with 2 or fewer articles each. Among the included systematic reviews, 13 focused on Curcumin, 12 on Coffee or Tea, 10 on bioactive substance combinations, 6 on Resveratrol, and 2 each on Silymarin and Artichoke Leaf. The included studies showed substantial heterogeneity in reported outcomes, which primarily focused on hepatic health, body weight, adverse events, glycemic control, blood lipids, and body composition. Conclusions: This scoping review highlights a range of bioactive substances used in the treatment of MASLD. While evidence is abundant for bioactive substances like Curcumin and Silymarin, further research and synthesis of findings is necessary to establish the clinical efficacy of all bioactive substances. Full article

Background/Objectives: This research investigated the effects of myricitrin on hypercholesterolemia and non-alcoholic fatty liver disease (NAFLD) in mice given a high-cholesterol diet (HCD). Methods: C57BL/6J mice were maintained for 20 weeks on an HCD with or without myricitrin. Results: Myricitrin had no impact on the food consumption, body weight, or plasma triglyceride concentrations. However, myricitrin-supplemented mice had lower plasma total cholesterol (TC) concentrations and LDL + VLDL-cholesterol/TC proportion, and higher HDL-cholesterol/TC proportion than control mice, which resulted in a markedly decreased atherogenic index. Moreover, the levels of plasma C-reactive protein, oxidized LDL, lipoprotein(a), and plasminogen activator inhibitor-1, which are indicators for cardiovascular disease (CVD), were reduced, while levels of plasma paraoxonase, a cardioprotective enzyme, were greater in myricitrin-supplemented mice than in control mice. Myricitrin also meaningfully reduced liver weight and hepatic cholesterol content, and slightly alleviated fatty liver and fibrosis caused by an HCD. The plasma and hepatic cholesterol-lowering effects of myricitrin were partly associated with decreased activities of hepatic 3-hydroxy-3-methylglutaryl-CoA reductase and acyl-CoA:cholesterol acyltransferase, which are involved in cholesterol synthesis and esterification, respectively, as well as mRNA expression. Myricitrin also altered other hepatic genes implicated in cholesterol homeostasis, including the downregulation of SREBP2 and ABCA1 mRNA expression and the upregulation of LDLR mRNA expression. Moreover, myricitrin decreased TBARS levels in the liver and erythrocytes by activating antioxidant enzymes (SOD and catalase). Conclusions: These results indicate that dietary myricitrin may offer therapeutic benefits for HCD-caused hypercholesterolemia and NAFLD, and may help reduce CVD risk. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the novel terminology encompassing liver disease associated with metabolic dysfunction, replacing the previous terminology of non-alcoholic fatty liver disease (NAFLD). This disease is strongly associated with metabolic disorders such as obesity, type 2 diabetes, and dyslipidemia. MASLD and dyslipidemia are deeply interconnected, driven by shared pathophysiological mechanisms. Emerging evidence suggests that statins, a class of lipid-lowering medications, may have beneficial effects on MASLD beyond their primary role in reducing cholesterol levels through several mechanisms, including anti-inflammatory, antioxidant, anti-fibrosis, and immunomodulatory effects. This review aims to summarize the efficacy of statins in the management of MASLD and provide insights into their potential mechanisms of action. It discusses the pathophysiology of MASLD and the role of statins in targeting key aspects of the disease. Additionally, the review examines the clinical evidence supporting the use of different statins in MASLD treatment and highlights their specific effects on liver enzymes, inflammation, and fibrosis. Furthermore, an algorithm for statin therapy in MASLD is proposed based on the current knowledge and available evidence. Full article

Background: Asymptomatic liver steatosis constitutes an emerging issue worldwide. Therefore, we decided to explore relationships between selected types of microRNAs (miRNAs), serological markers of liver fibrosis and hematological parameters in the course of non-alcoholic fatty liver disease (NAFLD). Methods: Two hundred and seven persons were included in the survey: 97 with NAFLD and 110 healthy controls. Serological concentrations of miR-126-3p, miR-197-3p, and miR-1-3p were measured in all participants. Direct indices of liver fibrosis [procollagen I carboxyterminal propeptide (PICP), procollagen III aminoterminal propeptide (PIIINP), platelet-derived growth factor AB (PDGF-AB), transforming growth factor-α (TGF-α) and laminin] together with indirect markers (AAR, APRI, FIB-4 and GPR) were also evaluated. The assessment of hematological parameters concerned: mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (PCT), red blood cell distribution width (RDW), MPV to platelet (PLT) ratio (MPR), RDW to PLT ratio (RPR), neutrophil to lymphocyte (LYM) ratio (NLR), PLT to LYM ratio (PLR) and RDW to LYM ratio (RLR). Additionally, the NAFLD fibrosis score and BARD score were applied. Results: The concentration of miR-126-3p and miR-1-3p was higher, and miR-197-3p was lower in the NAFLD group (p < 0.0001). miR-197-3p correlated notably with hematological indices: negatively with PDW (p < 0.05) and positively with PLR (p < 0.05). Conclusions: Significant correlations between miRNA molecules and hematological markers in the course of NAFLD indicate inflammation as a potential background and create new possibilities for a diagnostic approach. Full article

Background/Objectives: Fructose-driven metabolic disorders, such as obesity, non-alcoholic fatty liver disease (NAFLD), dyslipidemia, and type 2 diabetes, are significant global health challenges. Ketohexokinase C (KHK-C), a key enzyme in fructose metabolism, is a promising therapeutic target. α-Mangostin, a naturally occurring prenylated xanthone, has been identified as an effective KHK-C inhibitor, prompting exploration of its analogs for enhanced efficacy. This study aimed to identify α-Mangostin analogs with improved inhibitory properties against KHK-C to address these disorders. Methods: A library of 1383 analogs was compiled from chemical databases and the literature. Molecular docking, binding free energy calculations, pharmacokinetic assessments, molecular dynamics simulations, and quantum mechani–cal analyses were used to screen and evaluate the compounds. α-Mangostin’s binding affinity (37.34 kcal/mol) served as the benchmark. Results: Sixteen analogs demonstrated binding affinities superior to α-Mangostin (from −45.51 to −61.3 kcal/mol), LY-3522348 (−45.36 kcal/mol), and reported marine-derived inhibitors (from −22.74 to −51.83 kcal/mol). Hits 7, 8, 9, 13, and 15 not only surpassed these benchmarks in binding affinity, but also exhibited superior pharmacokinetic properties compared to α-Mangostin, LY-3522348, and marine-derived inhibitors, indicating strong in vivo potential. Among these, hit 8 emerged as the best performer, achieving a binding free energy of −61.30 kcal/mol, 100% predicted oral absorption, enhanced metabolic stability, and stable molecular dynamics. Conclusions: Hit 8 emerged as the most promising candidate due to its superior binding affinity, favorable pharmacokinetics, and stable interactions with KHK-C. These findings highlight its potential for treating fructose-driven metabolic disorders, warranting further experimental validation. Full article

Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease and is closely associated with metabolic diseases such as obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome. However, effective treatment strategies for NAFLD are still lacking. In recent years, progress has been made in understanding the pathogenesis of NAFLD, identifying multiple therapeutic targets and providing new directions for drug development. This review summarizes the recent advances in the treatment of NAFLD, focusing on the mechanisms of action of natural products, small-synthetic-molecule drugs, and combination therapy strategies. This review aims to provide new insights and strategies in treating NAFLD. Full article

Endocrine-disrupting chemicals (EDCs), including phthalates, have been implicated in the development of non-alcoholic fatty liver disease (NAFLD) and hepatic fibrosis. This study investigates the age-dependent effects of butyl benzyl phthalate (BBP) exposure on lipid metabolism in the livers of young and aged mice. Young (2-month-old) and aged (20-month-old) male C57BL/6 mice were exposed to BBP through drinking water at a dose of 169 μg/kg/day for 6 and 4 months, respectively. Young mice exposed to BBP showed fatty liver, with downregulation of key fatty acid oxidation genes (CPT1A, CPT1B, CPT2, and Acox1) and elevated pro-inflammatory cytokines (TNF-α and IL-6). In contrast, aged mice exhibited hepatic fibrosis, with increased collagen deposition and upregulation of genes related to fibrosis (Acta2, MMP2, TGF-ß1, and Col1a2), cirrhosis (CXCR4, SOX9, DCN, and MFAP4), and cancer (Bcl2, CDKN2a, c-Myc, and Fn1). Overall, these findings emphasize the importance of age when evaluating the risks of EDC exposure, such as BBP. Future research should focus on understanding the molecular mechanisms behind these age-related differences and explore Grem1 and SOCS3 as potential therapeutic targets for treating EDC-induced and age-related liver diseases. Full article

Objectives: This study aimed to investigate the association between nonalcoholic fatty liver disease (NAFLD), assessed by the Fatty Liver Index (FLI), and the occurrence of lung abscess within a large population-based cohort. Method: We conducted a nationwide retrospective study using data from 367,930 subjects who underwent National Health check-ups between 2009 and 2018. Cox proportional hazards regression was performed to evaluate the association between the FLI and the incidence of lung abscess and community-acquired pneumonia (CAP) after adjusting for age, sex, and relevant covariates. Results: Among the study population, 455 (0.12%) and 44,934 (12.2%) patients were diagnosed with lung abscesses and CAP, respectively. The cumulative incidence of lung abscess was higher in individuals with elevated FLI values (FLI < 30, 0.10%; 30 ≤ FLI < 60, 0.16%; FLI ≥ 60, 0.18%; p < 0.001), whereas the incidence of CAP decreased across FLI groups (FLI < 30, 12.4%; 30 ≤ FLI < 60, 12.3%; FLI ≥ 60, 11.0%; p < 0.001). After adjusting for covariates, the risk of lung abscess significantly increased in the 30 ≤ FLI < 60 (Hazard ratio (HR) = 1.26; 95% confidence interval (CI), 0.95–1.68; p = 0.115) and the FLI ≥ 60 (HR = 1.67; 95% CI, 1.37–2.29; p < 0.001) groups, although the risk of CAP was relatively small in both groups (30 ≤ FLI < 60; HR = 1.06; 95% CI, 1.03–1.09; p < 0.001) (FLI ≥ 60; HR = 1.13; 95% CI, 1.08–1.12; p < 0.001). Conclusions: Our study provides compelling evidence supporting a potential link between NAFLD, as measured by FLI, and the incidence of lung abscess. These findings suggest the importance of vigilant monitoring of respiratory health in patients with NAFLD and emphasise the need for early detection of possible complications. Full article

Background and Objectives: High fructose intake is associated with non-alcoholic fatty liver disease (NAFLD), a chronic liver disease that is on the rise worldwide. New alternatives for treatment, such as bioactive phytochemicals, are needed. The aim of this study was to investigate the beneficial role of resveratrol in treating non-alcoholic steatohepatitis (NASH). Materials and Methods: Sixty male albino rats were allocated to three groups: group I, the normal control group; group II, the fructose-enriched diet group (FED), which was fed a 70% fructose diet for six weeks to induce NASH; and group III, the resveratrol–FED group (RES + FED), which was given the same FED diet plus an oral dose of 70 mg/kg resveratrol (RES) every day for an additional six weeks. We performed histological evaluations and assessed blood lipids and liver enzymes to study resveratrol’s impact on NASH. Quantitative real-time PCR was used to assess the mRNA expression of nuclear factor E2-related factor 2 (Nrf2) in the liver samples. ELISA was used to measure Beclin 1, AMPK, IL-6, and the DNA-binding activity of Nrf2. Oxidative stress indicators, including GSH, SOD, and MDA, were evaluated spectrophotometrically. Results: Resveratrol effectively alleviated the biochemical and histopathological abnormalities associated with NASH, improving autophagy by raising Beclin 1 levels while reducing inflammation by decreasing IL-6 levels. Furthermore, resveratrol restored the liver architecture and the oxidative balance, as evidenced by the decreased MDA levels and improved antioxidant status via elevated GSH and SOD activities, as well as the activation of the AMPK/Nrf2 signaling axis. Conclusions: This study specifically examines resveratrol’s therapeutic effects in a high-fructose diet-induced NASH model, focusing on the AMPK/Nrf2 signaling pathway to address oxidative stress and autophagy, providing novel insights into its molecular mechanism of action. Resveratrol reduces NASH by boosting autophagy and activating the AMPK/Nrf2 pathway. These findings underscore the potential of resveratrol as a promising therapeutic agent that can support treatment alongside conventional medications in the management of non-alcoholic steatohepatitis (NASH). Full article

Epigallocatechin gallate (EGCG) is the predominant bioactive catechin in green tea, and it has been ascribed a range of beneficial health effects. Current increases in obesity and non-alcoholic fatty liver disease (NAFLD) rates represent a persistent and burdensome threat to global public health. While many clinical studies have demonstrated that EGCG is associated with positive effects on various health parameters, including metabolic biomarkers, waist circumference, and body weight when consumed by individuals affected by obesity and NAFLD, there are also some reports suggesting that it may entail some degree of hepatotoxicity. The present review provides a comprehensive summary of the extant clinical findings pertaining to the safety and effectiveness of EGCG in managing obesity and NAFLD, with a particular focus on how treatment duration and dose level affect the bioactivity of this compound. Full article