Treatment Of Nonalcoholic Fatty Liver Disease Research Articles

Study the role of xanthine oxidase inhibitor, allopurinol in experimentally induced steatohepatitis

Nonalcoholic steatohepatitis (NASH) is a chronic liver disease which can lead to cirrhosis and hepatic failure. It is observed in patients with both type 1 and type 2 diabetes mellitus (T1DM, T2DM). Allopurinol, a xanthine oxidase inhibitor that is widely used in clinical practice, has been demonstrated to reduce hepatic oxidative stress and attenuate acute liver injury which may be through activation of antioxidant pathways. This work aimed at investigating the role of Allopurinol (ALP) in attenuation of type 1 diabetes associated with Nonalcoholic fatty liver disease (NAFLD) and exploring the possible molecular mechanism by which ALP attenuates NASH in type 1 diabetes. Forty-five adult male albino rats were included in the study. They were randomly allocated to 3 equal groups: group I (control), Group II (diabetic animals), Group III (diabetic animals with allopurinol treatment). At the end of this experimental study measurements of serum glucose, ALT, AST, cholesterol, triglyceride, serum levels of uric acid, malondialdehyde (MDA), serum superoxide dismutase (SOD) were done. Histological analysis of liver tissue to diagnose steatohepatitis and gene expression of nuclear factor-erythroid-2- related factor-2 (Nrf2) & TNFα were done. Diabetic rates treated with allopurinol (group III) showed decrease in serum levels of ALT, AST, cholesterol, uric acid and MDA compared to diabetic rat group. As regards TNF, gene expression was significantly decreased in group III compared to group II. This study also demonstrated that Nrf2α was significantly increased in group III compared to group II. Allopurinol also, ameliorated the histopathological changes observed in group II. In conclusion, allopurinol treatment increases the Nrf2 gene expression in the liver of STZ-induced diabetic rats and ameliorates steatohepatitis through modulation of TNF-α gene expression. Allopurinol could be a candidate for prevention or treatment of NAFLD.

The Impact of Sira Vedha (Phlebotomy) at the Right Elbow Joint in the Treatment of Non-Alcoholic Fatty Liver Disease - A Research Report

ABSTRACT Non-alcoholic fatty liver disease (NAFLD) affects 9%–53% of the Indian population. No Indian studies have examined Sira Vedha (phlebotomy) for NAFLD, although it has been studied for other conditions. Sushruta recommended Sira Vedha at the right elbow joint for liver diseases, but clinical evidence for its efficacy in NAFLD is lacking. This clinical trial aimed to generate evidence for Sira Vedha in NAFLD patients. One hundred eleven patients with Grade I/II NAFLD were randomly assigned to either a control group (diet and exercise) or an intervention group (Sira Vedha, diet, and exercise). Blood samples were collected for lipid profile and liver function tests before and after treatment. Results showed significant improvements in SGOT, SGPT, cholesterol, HDL, and triglyceride levels in the intervention group compared to the control group, supporting the efficacy of Sira Vedha in NAFLD treatment. This study highlights the need for clinical evidence to confirm traditional Ayurvedic practices.

Application and mechanism of Chinese herb medicine in the treatment of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver condition closely associated with metabolic syndrome, with its incidence rate continuously rising globally. Recent studies have shown that the development of NAFLD is associated with insulin resistance, lipid metabolism disorder, oxidative stress and endoplasmic reticulum stress. Therapeutic strategies for NAFLD include lifestyle modifications, pharmacological treatments, and emerging biological therapies; however, there is currently no specific drug to treat NAFLD. However Chinese herb medicine (CHM) has shown potential in the treatment of NAFLD due to its unique therapeutic concepts and methods for centuries in China. This review aims to summarize the pathogenesis of NAFLD and some CHMs that have been shown to have therapeutic effects on NAFLD, thus enriching the scientific connotation of TCM theories and facilitating the exploration of TCM in the treatment of NAFLD.

Daphnetin ameliorates hepatic steatosis by suppressing peroxisome proliferator-activated receptor gamma (PPARG) in ob/ob mice

Non-alcoholic fatty liver disease (NAFLD) is the predominant metabolic liver disorder and currently lacks effective and safe pharmaceutical interventions. Daphnetin (DA), a natural coumarin derivative with anti-inflammatory and antioxidant activities, is a promising agent for NAFLD treatment. In this study, we evaluated the effects and mechanisms of DA on hepatic lipid metabolism in ob/ob mice. Our results showed that DA effectively ameliorates glucose metabolism and hepatic lipid accumulation in ob/ob mice. Metabolomics and RNA sequencing (RNA-seq), combined with GEO data analysis, suggest that DA primarily modulates the peroxisome proliferator-activated receptor gamma (PPARG) pathway, as validated in vivo in ob/ob mice. Mechanistically, DA selectively targets PPARG in hepatic cells by inhibiting PPARG promoter activity and downregulating its expression, resulting in decreased transcription of downstream lipid metabolism-related genes, including fatty acid binding protein 4 (Fabp4), cluster of differentiation 36 (Cd36), and fatty acid synthase (Fasn). This effect was abolished in PPARG-deficient HepG2 cells subjected to palmitic acid (PA) insult. Our findings provide evidence that DA acts as a selective suppressor of hepatic PPARG, suggesting an attractive strategy by targeting PPARG for the prevention of hepatic steatosis.

Multiple Machine Learning Identifies Key Gene PHLDA1 Suppressing NAFLD Progression.

Non-alcoholic fatty liver disease (NAFLD) poses a serious global health threat, with its progression mechanisms not yet fully understood. While several molecular markers for NAFLD have been developed in recent years, a lack of robust evidence hampers their clinical application. Therefore, identifying novel and potent biomarkers would directly aid in the prediction, prevention, and personalized treatment of NAFLD. We downloaded NAFLD-related datasets from the Gene Expression Omnibus (GEO). Differential expression analysis and functional analysis were initially conducted. Subsequently, Weighted Gene Co-expression Network Analysis (WGCNA) and multiple machine learning strategies were employed to screen and identify key genes, and the diagnostic value was assessed using Receiver Operating Characteristic (ROC) analysis. We then explored the relationship between genes and immune cells using transcriptome data and single-cell RNA sequencing (scRNA-seq) data. Finally, we validated our findings in cell and mouse NAFLD models. We obtained 23 overlapping differentially expressed genes (DEGs) across three NAFLD datasets. Enrichment analysis revealed that DEGs were associated with Apoptosis, Parathyroid hormone synthesis, secretion and action, Colorectal cancer, p53 signaling pathway, and Biosynthesis of unsaturated fatty acids. After employing machine learning strategies, we identified one gene, pleckstrin homology like domain family A member 1 (PHLDA1), downregulated in NAFLD and showing high diagnostic accuracy. CIBERSORT analysis revealed significant associations of PHLDA1 with various immune cells. Single-cell data analysis demonstrated downregulation of PHLDA1 in NAFLD, with PHLDA1 exhibiting a significant negative correlation with macrophages. Furthermore, we found PHLDA1 to be downregulated in an in vitro hepatic steatosis cell model, and overexpression of PHLDA1 significantly reduced lipid accumulation, as well as the expression of key molecules involved in hepatic lipogenesis and fatty acid uptake, such as FASN, SCD-1, and CD36. Additionally, gene set enrichment analysis (GSEA) pathway enrichment analysis suggested that PHLDA1 may influence NAFLD progression through pathways such as Cytokine Cytokine Receptor Interaction, Ecm Receptor Interaction, Parkinson's Disease, and Ribosome pathways. Our conclusions were further validated in a mouse model of NAFLD. Our study reveals that PHLDA1 inhibits the progression of NAFLD, as overexpression of PHLDA1 significantly reduces lipid accumulation in cells and markedly decreases the expression of key molecules involved in liver lipogenesis and fatty acid uptake. Therefore, PHLDA1 may emerge as a novel potential target for future prediction, diagnosis, and targeted prevention of NAFLD.

Potential Mechanism of Perillaldehyde in the Treatment of Nonalcoholic Fatty Liver Disease Based on Network Pharmacology and Molecular Docking

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic metabolic liver diseases worldwide. Perillaldehyde (4-propyl-1-en-2-ylcyclohexene-1-aldehyde, PA) is a terpenoid compound extracted from Perilla, which has effective pharmacological activities such as anti-inflammatory, antidepressant, and anticancer. This study aimed to explore the pharmacological effects of PA in intervening with NAFLD and reveal its potential mechanisms. Firstly, we identified the core targets of PA intervention therapy for NAFLD through network pharmacology and molecular docking techniques. After that, in vitro animal experiments such as H&E and Masson staining, immunofluorescence, immunohistochemistry, and western blot were conducted to validate the results network effectively pharmacology predicted. Network pharmacology analysis suggested that PPAR-α may be the core target of PA intervention in NAFLD. H&E and Masson staining showed that after low-dose (50mg/kg) PA administration, there was a noticeable improvement in fat deposition in the livers of NAFLD mice, and liver tissue fibrosis was alleviated. Immunohistochemical and immunofluorescence analysis showed that low dose (50mg/kg) PA could reduce hepatocyte apoptosis, decrease the content of pro-apoptosis protein Bax, and increase the expression of anti-apoptosis protein Bcl-2 in NAFLD mice. Western blot results confirmed that low-dose (50mg/kg) PA could increase the expression of PPAR-α and inhibit the expression of NF-κB in NAFLD mice. Our study indicated that PA could enhance the activity of PPAR-α and reduce the level of NF-κB in NAFLD mice, which may positively affect the prevention of NAFLD.

Investigation of the mechanism by which Tegillarca granosa polysaccharide regulates non-alcoholic fatty liver disease in mice by modulating Lactobacillus Johnsonii

Non-alcoholic fatty liver disease (NAFLD), a prevalent chronic liver disease, is marked by excessive lipid deposition in the liver without alcohol abuse. Scapharca subcrenatum, a major Chinese farmed bivalve, yields S. subcrenatum polysaccharide (TGP), an active substance with known biological activity. Previous studies revealed TGP's significant regulatory effect on a high-fat diet (HFD)-induced NAFLD in mice. However, the precise mechanisms, particularly involving gut microbiota, remain unclear. In the current study, an antibiotic-treated mouse model was established to determine the mechanistic role of the gut microbiota in the observed anti-obesity effects of TGP. In addition, 16S rRNA genomic and metagenome-derived taxonomic analyses were performed to assess the gut microbial populations. The results showed that TGP selectively enhanced the number of the eosinophilic bacterium Lactobacillus johnsonii, which was reduced in HFD mice. Of note, the oral administration of L. johnsonii formulations to HFD mice alleviated NAFLD, and this was related to regulating lipid metabolism and the accumulation of lipids in the liver. Therefore, the current study uncovered a potential pathway for developing NAFLD treatment strategies based on the interaction between TGP and the gut microbiota.

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.

The Impact of SARS-CoV-2 on Liver Diseases and Potential Phytochemical Treatments

Abstract The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has brought about numerous challenges. One of these challenges is the impact of SARS-CoV-2 on the liver. Although this virus primarily affects the lungs, it can induce elevated transaminase levels and the development of scar tissue in the liver, exacerbating preexisting liver conditions. Individuals with preexisting conditions, such as non-alcoholic fatty liver disease (NAFLD), alcohol-induced liver disease (ALD), and hepatocellular carcinoma (HCC), face an increased risk of mortality from COVID-19. However, drugs currently used to treat COVID-19 have undesirable side effects that make them unsuitable for patients with pre-existing liver conditions. In this review, we explore the potential of phytochemicals, such as apigenin, berberine, curcumin, epigallocatechin-3-gallate, quercetin, resveratrol and silymarin, for treatment of the liver conditions NAFLD, ALD and HCC. We also discuss significant associations between phytochemicals and COVID-19 by depicting their molecular interactions. Based on the discussed overlapping functions, it is important to assess the therapeutic efficacy of phytochemicals that possess hepatoprotective properties as potential alternative COVID-19 treatments.

Exploring serum bile acids as potential noninvasive biomarkers for nonalcoholic fatty liver disease

BackgroundBile acids are vital regulators of liver metabolism, and their dysregulation is closely linked with the progression of nonalcoholic fatty liver disease (NAFLD). Profiling these bile acids may provide valuable diagnostic and prognostic markers for these conditions. This study aimed to evaluate bile acid profiles in NAFLD patients and assess their potential as biomarkers for diagnosing and predicting disease progression. Serum levels of 14 bile acids were measured in 25 normal healthy controls (NHC), 35patients with metabolic dysfunction–associated steatotic liver disease (MASLD), and 40 patients with NASH, categorized by the NAFLD Activity Score (NAS). Quantification was performed using high-performance liquid chromatography-tandem mass spectrometry (HPLC–MS/MS).ResultsPrimary unconjugated bile acids, CA and CDCA, along with conjugated acids GCA, GCDCA, TCA, and TCDCA, were significantly elevated in both MASLD and NASH compared to NHC (all p < 0.05). While levels increased progressively from NHC to MASLD to NASH, no significant differences were observed between MASLD and NASH except for GCA and TCA (P < 0.05). Similarly, secondary bile acids LCA, TLCA, GUDCA, and TUDCA were higher in MASLD and NASH compared to NHC (all p < 0.05).Logistic regression identified CA (odds ratio = 2.05, p = 0.02), CDCA (odds ratio = 1.58, p = 0.04), GCA (odds ratio = 1.92, p = 0.03) and DCA (odds ratio = 2.06, p = 0.04) as significant predictors of fibrosis. For active inflammation, GCA (odds ratio = 2.04, p = 0.04), and TCA (odds ratio = 1.94, p = 0.04) were significant predictors. In steatosis, CA, CDCA, GCA, DCA, TDCA, TLCA, and UDCA were notable predictors, with high odds ratios.ConclusionThe study highlights significant alterations in bile acid profiles associated with NAFLD progression. Specific bile acids, such as CA, GCA, TCA, and TCDCA are strong predictors of disease severity, indicating their potential as biomarkers for NAFLD treatment and prognosis.

Potential impact of ezetimibe on patients with NAFLD/NASH: a meta-analysis of randomized controlled trials.

Non-alcoholic fatty liver disease (NAFLD) is now the most common cause of chronic liver disease. Studies have found that ezetimibe may be utilized as a supplemental treatment for NAFLD. Additionally, many clinical trials reported the potential impacts of ezetimibe on patients with NAFLD, although some conclusions remain controversial. Therefore, this study aimed to evaluate the effects of ezetimibe on patients with NAFLD. Online search was conducted across databases including PubMed, Embase, Scopus, Web of Science, Cochrane Library, Wanfang, VIP, and CNKI to retrieve all relevant controlled studies on the treatment of NAFLD with ezetimibe from the inception of the databases until April 2024. This meta-analysis comprised 10 randomized controlled trials (RCTs). Statistical analysis was conducted using the Meta package in R v4.3.2. A total of ten RCTs were included in this study, encompassing 578 patients (290 in the ezetimibe group and 288 in the control group) diagnosed with NAFLD/non-alcoholic steatohepatitis (NASH). The results indicated that ezetimibe significantly reduced levels of aspartate aminotransferase (P < 0.01), glutamyl transferase (γ-GT) (P < 0.01), total cholesterol (P < 0.01), low-density lipoprotein cholesterol (P < 0.01), high-sensitivity C-reactive protein (P < 0.01), and interleukin-6 (P < 0.01), and markedly increased levels of glycated hemoglobin (P = 0.02). Ezetimibe may partially improve transaminase levels and positively impact liver function in patients with NAFLD/NASH. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023461467.

Stiff-Soft Hybrid Biomimetic Nano-Emulsion for Targeted Liver Delivery and Treatment of Early Nonalcoholic Fatty Liver Disease

Background: Nonalcoholic fatty liver disease (NAFLD) poses a risk for numerous metabolic diseases. To date, the U.S. Food and Drug Administration has not yet approved any medications for the treatment of NAFLD, for which developing therapeutic drugs is urgent. Dihydromyricetin (DMY), the most abundant flavonoid in vine tea, has been shown to be hepatoprotective. Its application was limited by low bioavailability in vivo; Methods: In order to improve the bioavailability of DMY and achieve liver-targeted delivery, we designed a DMY-loaded stiff-soft hybrid biomimetic nano drug delivery system (DMY-hNE). The in vivo absorption, distribution, pharmacokinetic profiles, and anti-NAFLD efficacy of DMY-hNE were studied; Results: DMY-hNE was composed of a stiff core and soft shell, which led to enhanced uptake by gastrointestinal epithelial cells and increased penetration of the mucus barrier, thus improving the in vivo absorption, plasma DMY concentration, and liver distribution versus free DMY. In an early NAFLD mouse model, DMY-hNE effectively ameliorated fatty lesions accompanied with reduced lipid levels and liver tissue inflammation; Conclusions: These findings suggested that DMY-hNE is a promising platform for liver drug delivery and treatment of hepatopathy.

7492 Fibroblast Growth Factor 21 In The Diagnosis And Treatment Of Metabolic Disorders

Abstract Disclosure: H.M. Heshmati: None. H.S. Abu-Lebdeh: None. Background: Fibroblast growth factor 21 (FGF21), a member of the human FGF superfamily, is a 181 amino acid peptide hormone primarily produced by the liver. The gene of FGF21, located on chromosome 19, was cloned in 2000. FGF21 is involved in the maintenance of metabolic homeostasis. This review presents an update on the relevance of FGF21 in the diagnosis and treatment of metabolic disorders including obesity, nonalcoholic fatty liver disease (NAFLD), dyslipidemia, and type 2 diabetes. Methods: A systematic search of literature was conducted using the search terms fibroblast growth factor 21, obesity, nonalcoholic fatty liver disease, dyslipidemia, and type 2 diabetes. Results: FGF21 is a stress hormone with effects on energy expenditure and metabolism of lipids and glucose. FGF21 exerts its endocrine action in the central nervous system and adipose tissue. The serum FGF21 levels in normal subjects increase with aging. Stressful conditions (e.g., fasting status, protein restriction, exercise, metabolic disorders, kidney diseases, cardiovascular diseases, and sepsis) increase FGF21 secretion. Serum FGF21 levels are increased in obesity, NAFLD, dyslipidemia, and type 2 diabetes. Some of these patients may have a state of FGF21 resistance. The resistance to FGF21 is related, at least in part, to the presence of high circulating levels of fibroblast activation protein, a protease that inactivates FGF21. It has been suggested that the exercise-induced weight loss can be due to increased FGF21 secretion and decreased FGF21 resistance in adipose tissue. Serum FGF21 level has the potential to be used as a biomarker for early diagnosis of metabolic disorders (e.g., NAFLD and type 2 diabetes). Based on different metabolic properties of FGF21, FGF21-based therapy has been considered as an attractive approach for the treatment of metabolic disorders. Since native FGF21 has poor pharmacodynamic properties (e.g., short half-life and proteolytic cleavage by proteases), long-acting FGF21 analogs (e.g., LY2405319, PF-05231023, pegozafermin, AKR-001, and LLF580) have been synthesized and tested in clinical trials for the treatment of obesity, NAFLD, dyslipidemia, and type 2 diabetes. The available results show that FGF21 analogs can reduce body weight, liver fat, blood lipids, and fasting insulin/insulin resistance. Overall, the treatment with these analogs is safe and well tolerated. Conclusion: FGF21 is a predominantly liver-derived peptide hormone regulating energy expenditure and metabolism of lipids and glucose. Serum FGF21 levels are increased in several metabolic disorders including obesity, NAFLD, dyslipidemia, and type 2 diabetes. FGF21 is an attractive target for the treatment of these metabolic disorders. Despite some promising results observed with the use of FGF21 analogs, more clinical studies are needed before recommending FGF21-based therapies in metabolic disorders. Presentation: 6/2/2024

A Systematic Review of the Beneficial Effects of Berry Extracts on Non-Alcoholic Fatty Liver Disease in Animal Models.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries and is strongly associated with several metabolic disorders. Plant-derived bioactive extracts, such as berry extracts, with high antioxidant capacity have been used for the treatment and prevention of this pathology. Moreover, they promote circular economy and sustainability. To study the beneficial effects of extracts from different parts of berry plants in animal models of NAFLD. A systematic research of the MEDLINE (via PubMed), Cochrane, and Scopus databases was conducted to identify relevant studies published after January 2011. In vivo animal studies of NAFLD were included in which berry extracts of different parts of the plant were administered and significantly improved altered biomarkers related to the pathology, such as lipid metabolism and hepatic steatosis, glucose and glycogen metabolism, and antioxidant and anti-inflammatory biomarkers. Of a total of 203 articles identified, 31 studies were included after implementation of the inclusion and exclusion criteria. Most of the studies showed a decrease in steatosis and a stimulation of genes related to β-oxidation and downregulation of lipogenic genes, with administration of berry extracts. Berry extracts also attenuated inflammation and oxidative stress. Administration of berry extracts seems to have promising potential in the design of enriched foodstuffs or nutraceuticals for the treatment of NAFLD.

Schisandrin A alleviates non-alcoholic fatty liver disease by improving liver metabolic disorders and suppressing the GSK3β signaling pathway

Non-alcoholic fatty liver disease (NAFLD) is a clinical pathological syndrome characterized by excessive fat deposition in liver cells, posing a new challenge in the field of contemporary medicine. Schisandrin A (SchA) is a lignan derived from the fruit of Schisandra chinensis, a functional food and also a traditional herbal medicine known for its hepatic protective effects. The study aims to identify potential target and regulation mechanism of SchA on NAFLD treatment. Metabolomics analysis revealed that SchA improved the abnormal metabolic profile of the liver in NAFLD mice. In addition to ameliorating lipid metabolism, SchA showed potential in elevating the levels of amino acids such as L-tryptophan, beta-alanine, L-aspartic acid, and L-tyrosine, which were deficient in NAFLD mouse livers, as well as restored the metabolism of abnormal vitamins like vitamin B6. Network pharmacology research and molecular docking suggested that GSK3β was a direct target of SchA, which was experimentally validated as well. These findings highlight the potential value of the active component SchA from Schisandra chinensis in the prevention and treatment of NAFLD.

Acupuncture, a Promising Therapy for Insulin Resistance and Non-Alcoholic Fatty Liver Disease.

Insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD) are representative metabolic diseases, and no pharmacological therapeutic strategies have been developed worldwide. In recent studies, acupuncture has increasingly been used as an integrative or complementary therapy for IR and NAFLD. In this review, we summarized 18 clinical trials and 25 animal studies to reveal the function and potential molecular mechanisms of acupuncture for IR and NAFLD treatment. We found that acupuncture can be a first-line treatment strategy for IR and has a positive therapeutic effect on NAFLD. Thus, this review provides clinicians with a deeper understanding of the scientific evidence for acupuncture treatment of IR and NAFLD. Finally, we highlighted three potential limitations of existing studies on acupuncture for the treatment of IR and NAFLD, including small sample sizes and inconsistent operating techniques.

Non-alcoholic fatty liver and periodontal disease in the adult population: Overview of systematic reviews

Introduction: Periodontal disease is a chronic inflammatory condition affecting the periodontal supporting tissues. In addition to dental loss, it has been associated with various metabolic disorders, including obesity, diabetes, dyslipidemia, and non-alcoholic fatty liver disease (NAFLD). This study aimed to analyze the effects of periodontal disease on the prevention and treatment of NAFLD in the adult population. Method: An electronic search of systematic reviews published between 2019 and 2024 was conducted in the Medline, Scopus, and Web of Science databases, as well as in the Epistemonikos meta-search engine. The search strategy was "Non-alcoholic Fatty Liver Disease AND Periodontitis". A total of 47 articles were identified, of which three systematic reviews with meta-analyses were analyzed. Results: The results indicated a potential association between periodontal disease and NAFLD, with an odds ratio (OR) of 1.48 (95% CI: 1.15 to 1.89; I² = 92%) and 1.91 (95% CI: 1.21 to 3.02; I² = 95%). However, this link has not been definitively proven, as heterogeneity decreases and the number of patients increases, resulting in an OR of 1.04 (95% CI: 0.97 to 1.12; I² = 58%). Conclusion: It is suggested that systemic inflammation and pro-inflammatory markers may play a significant role in the pathophysiology of both conditions. Nonetheless, further studies are needed to clarify this relationship and explore the common metabolic parameters.

Understanding Insulin Resistance in NAFLD: A Systematic Review and Meta-Analysis Focused on HOMA-IR in South Asians.

Non-alcoholic fatty liver disease (NAFLD), a metabolic condition, is becoming increasingly common in South Asia. While its clinical diagnosis primarily relies on sonography and altered hepatic biomarkers, the significance of non-hepatic indicators, such as Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), in relation to NAFLD requires further examination in the South Asian population due to ethnic differences in these markers. This study examined the relationship between insulin resistance, quantified using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), and NAFLD, along with other non-hepatic biomarkers. A thorough literature review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched the PubMed, Embase, and Google Scholar databases, yielding 287 articles. After applying the selection criteria and screening, 22 studies were selected for inclusion in the analysis. We extracted and meta-analyzed the data on HOMA-IR in patients with NAFLD, along with other relevant parameters. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of observational studies, whereas the RoB 2.0 tool was employed for randomized controlled trials (RCTs). The systematic review uncovered that individuals with NAFLD demonstrated statistically significant elevations in HOMA-IR levels, with a weighted mean difference (WMD) of 1.28 (95% confidence interval (CI): 1.00-1.58, I² = 98%, p < 0.0001) when compared to healthy subjects. Additionally, NAFLD patients showed markedly higher fasting blood glucose (FBG) levels, with a combined mean difference of 15.64 mg/dL (95% CI: 11.03-20.25, I² = 92%, p < 0.0001). The analysis also revealed increased triglyceride levels in NAFLD patients, with a pooled mean difference of 42.49 mg/dL (95% CI: 29.07-55.91, I² = 97%, p < 0.0001), and elevated C-reactive protein (CRP) levels, with a pooled mean difference of 2.17 mg/L (95% CI: 2.01-2.33, I² = 23%, p < 0.0001). Interestingly, subgroup analysis indicated that obese NAFLD patients exhibited significantly higher HOMA-IR levels than their non-obese counterparts, with a weighted mean difference of 5.85 (95% CI: 4.88-6.81, I² = 0%, p < 0.0001). Variations in study methodology, diagnostic techniques, and subject demographics were identified as sources of heterogeneity. The analysis found little evidence of publication bias, which lends credibility to the results. In South Asian populations, higher HOMA-IR, triglyceride-glucose (TyG) index, and CRP levels are associated with an increased risk of NAFLD. To improve the understanding and treatment of NAFLD in this specific demographic group, it is necessary to establish uniform diagnostic criteria and conduct additional studies, particularly RCTs.

Branched-chain amino acids alleviate NAFLD via inhibiting de novo lipogenesis and activating fatty acid β-oxidation in laying hens

The adverse metabolic impacts of branched-chain amino acids (BCAA) have been elucidated are mediated by isoleucine and valine. Dietary restriction of isoleucine promotes metabolic health and increases lifespan. However, a high protein diet enriched in BCAA is presently the most useful therapeutic strategy for nonalcoholic fatty liver disease (NAFLD), yet, its underlying mechanism remains largely unknown. Fatty liver hemorrhagic syndrome (FLHS), a specialized laying hen NAFLD model, can spontaneously develop fatty liver and hepatic steatosis under a high-energy and high-protein dietary background that the pathogenesis of FLHS is similar to human NAFLD. The mechanism underlying dietary BCAA control of NAFLD development in laying hens remains unclear. Herein, we demonstrate that dietary supplementation with 67 % High BCAA has unique mitigative impacts on NAFLD in laying hens. A High BCAA diet alleviates NAFLD, by inhibiting the tryptophan-ILA-AHR axis and MAPK9-mediated de novo lipogenesis (DNL), promoting ketogenesis and energy metabolism, and activating PPAR-RXR and pexophagy to promote fatty acid β-oxidation. Furthermore, we uncover that High BCAA strongly activates ubiquitin-proteasome autophagy via downregulating UFMylation to trigger MAPK9-mediated DNL, fatty acid elongation and lipid droplet formation-related proteins ubiquitination degradation, activating PPAR-RXR and pexophagy mediated fatty acid β-oxidation and lipolysis. Together, our data highlight moderating intake of high BCAA by inhibiting the AHR/MAPK9 are promising new strategies in NAFLD and FLHS treatment.

Current strategies for nonalcoholic fatty liver disease treatment (Review).

Nonalcoholic fatty liver disease (NAFLD), the most common chronic hepatic disease, has become a leading health problem worldwide. The present review summarized the methods and mechanisms to treat NAFLD, including the Mediterranean diet, physical activity and exercise, bariatric surgery and specific therapeutic agents, including statins, peroxisome proliferator‑activated receptor agonists, cenicriviroc and farnesoid X receptor agonists. Biologically active substances, such as peptides, alkaloids, polyphenolic compounds, silymarin, antibiotics, fatty acids, vitamins, probiotics, synbiotics and lamiaceae have also demonstrated actions that combat NAFLD. Considering their different mechanisms of action, combining some of them may prove an efficacious treatment for NAFLD. In this light, the present review describes recent progress and future prospects in treating NAFLD.