Nonalcoholic Fatty Liver Disease Research Articles

The Efficacy of Flaxseed Oil on Non-Alcoholic Fatty Liver Disease: A Randomized Controlled Trial

BackgroundNon-Alcoholic Fatty Liver Disease (NAFLD) is a prevalent liver disorder and a leading cause of elevated liver enzymes. Previous research indicates that a diet rich in polyunsaturated fatty acids (PUFAs) can alleviate liver insulin resistance. This study investigates the therapeutic effects of flaxseed oil, a primary PUFA source, on NAFLD treatment. In a randomized clinical trial comprising 60 NAFLD patients diagnosed with NAFLD of grades 1, 2, and 3, participants were assigned to either a flaxseed oil capsule group or a placebo group for 2 months. Before the intervention, both groups showed no significant differences in examined parameters. However, after the intervention, the flaxseed oil group exhibited significant improvements in Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), fasting blood sugar (FBS), and total bilirubin compared to the placebo group. Specifically, reductions were observed in AST (p=0.010), ALT (p=0.047), ALP (p<0.001), FBS (p=0.016), and total bilirubin (p=0.004). These findings suggest that flaxseed oil may hold promise as a therapeutic intervention for NAFLD, highlighting its potential in managing liver disease and metabolic parameters.

Changes in intestinal flora associated with childhood sleep-disordered breathing and the pathogenesis of non-alcoholic fatty liver disease in children

Objective:To explore the interaction between pediatric sleep-disordered breathing（SDB）, the intestinal microbiota, and pediatric non-alcoholic fatty liver disease（NAFLD）. Methods:A total of 63 non-obese children（47 children with SDB in the experimental group and 16 without SDB in the control group） were enrolled in this study. The liver function and degree of SDB were assessed in both groups. High-throughput 16S rRNA sequencing was conducted to detect the composition and functional variations of the intestinal microbiota in the two groups of children. Results:Compared with children in the experimental group, serum ALT and AST levels were higher in the control group. and the relative proteobacteria abundance of intestinal flora increased, and the relative abundance of Bacteroidetes decreased significantly. Function including membrane transport, carbohydrate metabolism and lipid metabolism, were enriched in the intestinal microbiota of children with SDB. Conclusion:The composition and functional annotation of the pediatric liver functional status and gut microbiota were significantly different between the two groups of children with and without SDB. Changes in SDB-associated intestinal bacterial abundance may be related to the pathogenesis of pediatric NAFLD.

Evaluating the therapeutic effect of different forms of silymarin on liver status and expression of some genes involved in fat metabolism, antioxidants and anti-inflammatory in older laying hens.

Silymarin, the predominant compound of milk thistle, is an extract took out from milk thistle (Silybum marianum) seeds, containing a mixture of flavonolignans with strong antioxidant capability. The experiment was conducted using 70 Lohmann LSL-Lite hens at 80 weeks of age with 7 treatments each with 10 replicates. Treatments included: (1) control diet without silymarin, (2) daily intake of 100mg silymarin powder/kg body weight (BW) (PSM100), (3) daily intake of 200mg silymarin powder/kg BW (PSM200), (4) daily intake of 100mg nano-silymarin/kg BW (NSM100), (5) daily intake of 200mg nano-silymarin/kg BW (NSM200), (6) daily intake of 100mg lecithinized silymarin/kg BW (LSM100) and (7) daily intake of 200mg lecithinized silymarin/kg BW (LSM200). The birds were housed individually, and diets were fed for 12 weeks. Scanning electron microscopy showed that NSM was produced with the average particle size of 20.30nm. Silymarin treatment improved serum antioxidant enzyme activity. All groups receiving silymarin showed a decrease in liver malondialdehyde content, expression of fatty acid synthase, tumour necrosis factor alpha, interleukin 6 (IL-6) genes in the liver, and hepatic steatosis than the control, except those fed the PSM100 diet. There were decreases in liver dry matter and fat contents, non-alcoholic fatty liver disease and hepatocyte ballooning, and an increase in glutathione peroxidase gene expression and a decrease in iNOS gene expression in birds fed the NSM100, NSM200, LSM100 and LSM200 diets compared to the control group. Moreover, all groups receiving silymarin showed a significant decrease in liver weight compare to the control group. Overall, the effects of silymarin when converted to NSM or LSM and offered at the level of 200mg/kg BW were more pronounced on the hepatic variables and may be useful in the prevention of the liver disease in older laying hens.

A lipid droplet-targeting fluorescence probe for monitoring of lipid peroxidation in ferroptosis and non-alcoholic fatty liver disease

Ferroptosis is a new regulated cell death process executed by lipid peroxidation (LPO) of polyunsaturated fatty acids. Lipid droplets (LDs), as an important organelle for lipid storage and metabolism, are probably a major site of LPO and play critical roles in the regulation of ferroptosis. However, the detailed study on LPO in LDs has not been carried out because of the lack of LD-targeting tools for the in situ monitoring of LPO. Herein, the first LD-targeting LPO fluorescence probe (LD-LPO) has been developed. LD-LPO exhibits a rapid and selective fluorescence enhancement at 518 nm, which is unaffected by highly destructive reactive oxygen species (e.g., hydroxyl radical) and environmental factor changes (e.g., polarity and viscosity). LD-LPO is capable of targeting LDs and visualizing LPO within LDs in situ during erastin- or (1S,3R)-RSL3 (RSL3)-induced ferroptosis. Moreover, LD-LPO has also been used to image LPO in the ferroptosis-associated non-alcoholic fatty liver disease (NAFLD), and to evaluate the medicine treatment of NAFLD with saroglitazar, demonstrating its utility for monitoring LPO levels in biosystems. The favorable analytical and imaging performance of LD-LPO may allow its application in more ferroptosis-associated physiological and pathological processes.

Waist-to-hip ratio and nonalcoholic fatty liver disease: a clinical observational and Mendelian randomization analysis

Waist-to-hip ratio and nonalcoholic fatty liver disease: a clinical observational and Mendelian randomization analysis

Association of Triglyceride and Glucose Index with Non-Alcoholic Fatty Liver Disease in Type 2 Diabetes Mellitus Patients

Association of Triglyceride and Glucose Index with Non-Alcoholic Fatty Liver Disease in Type 2 Diabetes Mellitus Patients

Systematic Review and Meta-analysis of the Impact of Metabolic Surgery on Hepatic Stiffness.

Bariatric surgery is one of the effective therapeutic options for people with obesity and obesity-related co-morbidities. In addition to weight-related co-morbid diseases, including diabetes, hypertension, and hypercholesterolemia, non-alcoholic fatty liver disease (NAFLD) is common in patients with morbid obesity. Bariatric surgery is one of the therapeutic options in the management of NAFLD. Hence, this review focused on the potential role of bariatric surgery on hepatic elasticity measured through shear wave elastography. A systematic literature search was performed, and the studies regarding heterogeneity were evaluated using the random-effects model. The meta-analysis on 6 trials (3-12 months follow-up) including 350 participants showed a significant reduction of liver elasticity after surgery (WMD: -1.149, 95% CI: -1.767, -0.532, p < 0.001; I2:81.55%). Bariatric surgery is associated with decreased liver elasticity. This improvement could be related to weight loss or other mechanisms of bariatric surgery.

Microplastics in the Human Body: Exposure, Detection, and Risk of Carcinogenesis: A State-of-the-Art Review.

Background: Humans cannot avoid plastic exposure due to its ubiquitous presence in the natural environment. The waste generated is poorly biodegradable and exists in the form of MPs, which can enter the human body primarily through the digestive tract, respiratory tract, or damaged skin and accumulate in various tissues by crossing biological membrane barriers. There is an increasing amount of research on the health effects of MPs. Most literature reports focus on the impact of plastics on the respiratory, digestive, reproductive, hormonal, nervous, and immune systems, as well as the metabolic effects of MPs accumulation leading to epidemics of obesity, diabetes, hypertension, and non-alcoholic fatty liver disease. MPs, as xenobiotics, undergo ADMET processes in the body, i.e., absorption, distribution, metabolism, and excretion, which are not fully understood. Of particular concern are the carcinogenic chemicals added to plastics during manufacturing or adsorbed from the environment, such as chlorinated paraffins, phthalates, phenols, and bisphenols, which can be released when absorbed by the body. The continuous increase in NMP exposure has accelerated during the SARS-CoV-2 pandemic when there was a need to use single-use plastic products in daily life. Therefore, there is an urgent need to diagnose problems related to the health effects of MP exposure and detection. Methods: We collected eligible publications mainly from PubMed published between 2017 and 2024. Results: In this review, we summarize the current knowledge on potential sources and routes of exposure, translocation pathways, identification methods, and carcinogenic potential confirmed by in vitro and in vivo studies. Additionally, we discuss the limitations of studies such as contamination during sample preparation and instrumental limitations constraints affecting imaging quality and MPs detection sensitivity. Conclusions: The assessment of MP content in samples should be performed according to the appropriate procedure and analytical technique to ensure Quality and Control (QA/QC). It was confirmed that MPs can be absorbed and accumulated in distant tissues, leading to an inflammatory response and initiation of signaling pathways responsible for malignant transformation.

The Onset of Steatosis Occurs as Early as Seven Days and Progresses to Non-Alcoholic Steatohepatitis in a Pediatric Pig Model of Non-Alcoholic Fatty Liver Disease

BackgroundNon-alcoholic fatty liver disease (NAFLD) is a chronic and progressive condition that afflicts patients of all ages, including neonates. Previously, we reported that neonatal pigs fed formulas rich in medium-chain (MCFA) compared with those fed long-chain fatty acid (LCFA) for 21 d, developed panacinar steatosis with no changes in whole body obesity. ObjectivesThe objective of the present study was to examine the temporal onset and development of NAFLD in neonatal pigs in response to MCFA feeding. MethodsNeonatal pigs (n=18) were fed isocaloric MCFA or LCFA. Six pigs from each group were euthanized following 7, 14 or 21 d of feeding. Body composition was assessed before initiation and at the end of the feeding period using dual-energy X-ray absorptiometry. Liver fat content and liver morphological features were determined from photomicrographs and evaluated for NAFLD by a pathologist. ResultsLean mass and fat mass as a percentage of body weight were not different between formulas. However, liver weight (P = 0.001) and liver fat mass (P < 0.001) were greater for pigs in the MCFA compared with those in the LCFA group. Steatosis developed as early as 7 d in the MCFA compared with the LCFA fed pigs (P < 0.001). In addition, steatosis progressed in a portal to venous direction as MCFA feeding duration was increased (P = 0.02). Pigs diagnosed with NASH (P < 0.001) and greater non-alcoholic fatty liver disease scores were those in the MCFA group (P < 0.001). ConclusionsThese results suggest that the onset and progression of NAFLD from steatosis to NASH occurs rapidly in response to MCFA feeding. Moreover, periportal steatosis is the initial feature in the development of NAFLD before its progression to NASH. The development of NAFLD in neonates seems to occur independently of whole-body adiposity.

Copper oxide nanoparticles induce non-alcoholic fatty liver disease by disrupting bile acid homeostasis and perturbing the intestinal microbial homeostasis

The wide application of copper oxide nanoparticles (CuO NPs) in various fields such as medicine, food, agriculture, and animal husbandry can result in direct or indirect oral exposure of CuO NPs to the human body. Therefore, the research on the biosafety of CuO NPs is crucially important. However, previous research mainly concentrated on CuO NPs-induced oxidative stress, rather than the dysregulation of metabolic homeostasis. Our current finding indicates that CuO NPs can enter the systemic circulation and accumulate in the liver by being adopted by the colon and disrupting the intestinal barrier. Subsequently, CuO NPs can impair bile acid (BA) homeostasis through increased reabsorption of bile acids (BAs), ultimately leading to non-alcoholic fatty liver disease (NAFLD). Additionally, the direct stimulation from CuO NPs, damage to the gut barrier, and disruption of BA homeostasis can also disrupt microbial homeostasis in the intestines, including alterations in the composition and biological functions of gut microbiota, thereby triggering NAFLD. These findings deepen our understanding of the biosafety of CuO NPs and provide evidence for their role in disrupting physiological homeostasis.

The role of probiotics in the treatment of Non-Alcoholic Fatty Liver Disease (NAFLD): new insights based on meta-analysis and subgroup analysis

The role of probiotics in the treatment of Non-Alcoholic Fatty Liver Disease (NAFLD): new insights based on meta-analysis and subgroup analysis

Chemogenetic activation of hepatic G12 signaling ameliorates hepatic steatosis and obesity

ObjectiveHepatic steatosis, the early stage of nonalcoholic fatty liver disease (NAFLD), currently lacks targeted pharmacological treatments. G protein-coupled receptors (GPCRs) in hepatocytes differentially regulate lipid metabolism depending on their coupling profile of G protein subtypes. Unlike Gs, Gi, and Gq signaling, the role of G12 signaling in hepatic steatosis remains elusive. The objective of this study was to investigate the effect of G12 signaling on hepatic steatosis and obesity and its mechanisms. MethodsWe generated mice expressing a G12-coupled designer GPCR in a liver-specific manner. We performed phenotypic analysis in the mice under the condition of fasting (acute hepatic steatosis model) or high-fat diet feeding (chronic hepatic steatosis model). ResultsIn acute and chronic hepatic steatosis models, chemogenetic activation of hepatic G12 signaling suppressed the progression of hepatic steatosis. The treatment led to an increased triglyceride secretion with little effect on mitochondrial respiratory activity, fatty acid oxidation, de novo lipogenesis, and fatty acid uptake. Furthermore, in a high-fat-diet-induced obesity model, activation of the G12-coupled designer GPCR exerted anti-obesity effects with increased whole-body energy expenditure and fat oxidation. Anti-FGF21 antibody treatment showed that the anti-obesity effects of the hepatic G12D activation relied in part on the hepatokine FGF21. ConclusionsOur findings indicate that the activation of G12 signaling in the liver has the potential to prevent hepatic steatosis and obesity. This discovery provides a strong rationale for the development of drugs targeting G12-coupled GPCRs expressed in the liver.

Double Trouble: Metabolic Dysfunction-Associated Fatty Liver Disease in Fraternal Twins

Pediatric cases of metabolic dysfunction-associated fatty liver disease (MASLD, formerly termed non-alcoholic fatty liver disease (NAFLD) are a troubling new outcome of the pediatric obesity epidemic. Advising patients and families with this condition is challenging considering the nutrition needed to sustain developmentally appropriate growth in youth. Describing risk factors, comorbidities, management, and referrals for MASLD could improve surveillance and outcomes for this condition. MASLD is commonly seen with other comorbidities such as dyslipidemia, obstructive sleep apnea, type 2 diabetes, hypothyroidism, anxiety, and depression. Considerations of epigenetics, diabetes, and adverse childhood experiences will be explored as additional underlying contributors to MASLD. Screening patients for this condition in conjunction with other comorbidities is essential to preventing the progression to non-alcoholic steatohepatitis (NASH) and cirrhosis, as well as lowering the risk for hepatocellular carcinoma. This fraternal twin case report describes pertinent diagnostics, recommendations for referrals, follow-up consultations, and red flags for more advanced liver disease.

Research Progress of Natural Products with the Activity of Anti-nonalcoholic Steatohepatitis.

Nonalcoholic steatohepatitis (NASH), a multi-target disease, is becoming a global epidemic. Although several anti-NASH drug candidates are being evaluated in late-stage clinical trials, none have been approved by the FDA to date. Given the global prevalence of the disease, the lack of effective drugs, and the very limited therapeutic efficacy of most of the existing synthetic drugs focusing on a single target, there is an urgent need to continue to develop new therapeutic agents. In contrast, many natural products, including pure compounds and crude extracts, possess hepatoprotective activities. Usually, these natural components are characterized by multi-targeting and low side effects. Therefore, natural products are important resources for the development of new anti- NASH drugs. In this paper, we focus on reviewing the anti-NASH potential, structure, and some of the side effects of natural products based on structural classification. We hope this mini-review will help researchers design and develop new anti-NASH drugs, especially based on the structure of natural products.

Hyaluronic acid act as drug self-assembly chaperone and co-assembled with celalstrol for ameliorating non-alcoholic steatohepatitis

Nanoformulations of therapeutic drugs with diverse chemical structures are often complex to produce and lack a universal synthesis approach. Herein, we demonstrate that hyaluronic acid (HA) can function as an assembly chaperone, facilitating the formulation of various chemical compounds into nanoparticles without necessitating chemical modification. As a proof of concept, celastrol-HA co-assembled nanoparticles (CHNPs) were synthesized and utilized in the multifactorial treatment of non-alcoholic steatohepatitis (NASH). By simply blending an aqueous solution of HA and celastrol, we achieved the formation of homogeneous, stable, and biocompatible nanoparticles, effectively addressing the critical issues associated with celastrol's poor water solubility and high systemic toxicity. of celastrol. Ex vivo and in vivo experiments demonstrated that CHNPs ameliorated NASH by inhibiting macrophage M1 polarization, reducing liver inflammation and lipid deposition, and improving metabolic disorders. Furthermore, CHNPs reduced systemic toxicity and enhanced the bioavailability of celastrol. The simplicity of the HA-based nanoparticles may facilitate the development of translational nanomedicines.

Associations of four surrogate insulin resistance indexes with non-alcoholic steatohepatitis in Chinese patients with obesity: a cross-sectional study.

This study was designed to evaluate the association of four surrogate indexes of IR with NASH in patients with obesity. A total of 270 patients who underwent bariatric surgery, were included in this cross-sectional study. NASH was diagnosed based on liver biopsies. Binary logistics regression analyses were performed to assess the associations of four surrogate indexes of IR (HOMA-IR, Matsuda index, TyG, and TG/HDL-C) with NASH in patients with obesity. The restricted cubic spline was used to assess the dose-response associations of surrogate indexes of IR with NASH after adjusting for confounding factors. NASH was diagnosed in 136 patients, with a prevalence of 50.37%. Compared with tertile 1, the fully adjusted ORs (95% CIs) of NASH for tertile 3 were 2.711(1.113-6.608) and 0.297 (0.152-0.579) for TyG and Matsuda index. Consistently, per SD increment of TyG were still significantly associated with 64% increased risks of NASH, and per SD increment of Matsuda index were still significantly associated with 38% decreased risks of NASH. In contrast, no significant associations were found between HOMA-IR and TG/HDL-C and the risk of NASH in patients with obesity (all P > 0.05). After adjusting covariates in restricted cubic splines, the risk of NASH decreased with the increment of Matsuda Index levels (P-nonlinear = 0.442, P-overall = 0.007) and with the decrement of TyG levels (P-nonlinear = 0.004, P-overall = 0.001). In patients with obesity, TyG and Matsuda index were independently related to the risk of NASH after adjustment for traditional risk factors. In addition, compared with HOMA-IR and TG/HDL-C, the Matsuda index and TyG may be more suitable for NASH prediction in patients with obesity.

Management strategies for metabolic dysfunction-associated steatotic liver disease (MASLD).

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by hepatic steatosis that is confirmed by imaging or histology in the setting of at least 1 metabolic risk factor in the absence of significant alcohol consumption. Nonalcoholic steatohepatitis, or NASH, was recently renamed metabolic dysfunction-associated steatohepatitis (MASH); it represents the progressive form of MASLD. MASH is defined by hepatic steatosis, lobular inflammation, and ballooning degeneration (hepatocellular injury) in a characteristic histologic pattern. Multiple pathophysiologic mechanisms underlie the development of MASLD, and multiple factors (eg, metabolic, hormonal, genetic, nutritional, and epigenetic components) are related to liver injury. MASH has a prevalence in the United States of 1% to 6%, and it is expected to rise in the next decade. Individuals living with MASH frequently suffer from comorbidities such as type 2 diabetes and cardiovascular disease. Several guidelines have been published to support the timely diagnosis of MASH that incorporate noninvasive tests that obviate the need for liver biopsy. Multiple MASH treatment options are in various stages of development. The THR-β agonist resmetirom, approved by FDA in March 2024, offers a liver-directed treatment for those patients living with moderate to severe fibrosis without cirrhosis. Considering the progressive nature of the disease and the availability of a treatment that can be initiated early to halt MASH progression, patients who have risk factors for MASH should urgently be encouraged to visit their health care providers for MASH screening.

High-coverage targeted lipidomics revealed novel profile of serum lipid dysregulation in adult growth hormone deficiency.

Patients with adult growth hormone deficiency (AGHD) are at increased risk of metabolic syndrome. Despite extensive research efforts in recent decades, the lipid metabolism pattern of AGHD has yet to be thoroughly characterized. In this study, we used lipidomics analysis of fasting serum samples from 30 AGHD patients due to intracranial germ cell tumors (iGCTs) and 30 age-, gender-, and body mass index (BMI)-matched healthy controls to investigate the serum lipidomic pattern of AGHD patients due to iGCTs. We meticulously quantified 534 serum lipids from 29 classes using high-coverage targeted lipidomics technology in conjunction with a robust bioinformatics pipeline. Our results revealed an AGHD-specific dynamic change in serum lipidomic profile, manifested by higher overall levels of many lipid subclasses, including triacylglycerols (TAGs), diacylglycerols (DAGs), phosphatidylglycerols, phosphatidylethanolamines (PE), phosphatidylcholines (PC), phosphatidylinositols, ceramides, and bis(monoacylglycerol)phosphates than in healthy controls, and a distinct lowering level in alkyl PE (PE-O) and alkyl PC (PC-O). AGHD individuals with non-alcoholic fatty liver disease showed specific changes in higher TAG and DAG subclass levels. Alterations in lipid profiles may contribute to metabolic dysregulation in AGHD patients. TAGs, PCs, and PE-fatty acids positively correlated with BMI, fasting insulin, insulin resistance index, and adverse lipid parameters. In contrast, ether-linked PE-O, PC-O, and LysoPE-O showed a negative correlation. This study has significantly expanded the current understanding of lipid dysregulation in AGHD patients due to iGCT. These findings can potentially guide future research and the development of monitoring and intervention strategies.

Vine tea kombucha ameliorates non-alcoholic fatty liver disease in high-fat diet fed mice via antioxidation, anti-inflammation and regulation of gut microbiota

Vine tea kombucha ameliorates non-alcoholic fatty liver disease in high-fat diet fed mice via antioxidation, anti-inflammation and regulation of gut microbiota

Study on the Mechanism of Alpinia officinarum Hance in the Improvement of Insulin Resistance through Network Pharmacology, Molecular Docking and in vitro Experimental Verification.

Research has elucidated that the pathophysiological underpinnings of non-alcoholic fatty liver disease and type 2 diabetes mellitus are intrinsically linked to insulin resistance (IR). However, there are currently no pharmacotherapies specifically approved for combating IR. Although Alpinia officinarum Hance (A. officinarum) can ameliorate diabetes, the detailed molecular mechanism through which it influences IR has not been fully clarified. To predict the active components of A. officinarum and determine the mechanism by which A. officinarum affects IR. The active compounds and molecular mechanism underlying the improvement of IR by A. officinarum were predicted via network pharmacology and molecular docking. To further substantiate these predictions, an in vitro model of IR was induced in HepG2 cells using high glucose concentrations. Cytotoxicity and oxidative stress levels were evaluated using Cell Counting Kit-8, reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD) assay kits. The putative molecular mechanisms were corroborated through Western blot and RT-PCR analyses. Fourteen principal active components in A. officinarum, 133 potential anti-IR gene targets, and the top five targets with degree values were ALB, AKT1, TNF, IL6, and VEGFA. A. officinarum was posited to exert its pharmacological effects on IR through mechanisms involving lipid and atherosclerosis, the AGE-RAGE signaling pathway in diabetic complications, the PI3K-AKT signaling pathway, fluid shear stress, and atherosclerosis. Intriguingly, network pharmacology analysis highlighted (4E)-7-(4-hydroxy-3-methoxyphenyl)-1-phenylhept-4-en-3- one (A14) as the most active compound. Molecular docking studies further confirmed that A14 has a strong binding affinity for the main targets of PI3K, AKT, and Nrf2. The experiments demonstrated that A14 significantly diminished the ROS and MDA levels while augmenting the SOD activity. Moreover, A14 was found to elevate the protein expression of PI3K, AKT, Nrf2, and HO-1, and increase the mRNA levels of these targets as well as NQO1. A. officinarum could play a therapeutic role in IR through multiple components, targets, and pathways. The most active component of A. officinarum responsible for combating IR is A14, which has the ability to regulate oxidative stress in IR-HepG2 cells by activating the PI3K/AKT/Nrf2 pathway. These findings suggest a potential pharmacological intervention strategy for the treatment of IR.