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Alcohol‐associated liver disease (ALD), including alcoholic fatty liver, is a serious problem in many countries, and its economic costs to society are enormous. There is evidence indicating the relations between gut environments and liver disease, and thus, improvement of gut environment is expected to be an effective approach for ALD prevention. In this study, we explored the preventive effect of partially hydrolyzed guar gum (PHGG) on ALD focusing on the gut–liver axis. Two weeks of PHGG pre‐feeding suppressed the liver fat accumulation in the experimental binge alcohol model mouse. In cecal microbiome, PHGG pre‐feeding increased beneficial Bifidobacterium with its metabolite acetate concentration and suppressed the alcohol‐induced increase in the potential pathobiont Streptococcus. PHGG pre‐feeding increased colonic gene expression of angiogenin genes, which act as antimicrobial peptides and decreased expression of genes for mast cell protease, which suggests a potential involvement in leaky gut. Correlation network analysis based on evaluated parameters revealed four relations worth noticing. (i) The abundance of Bifidobacterium positively correlated with cecal acetate. (ii) Cecal acetate negatively correlated with Streptococcus via colonic angiogenin expression. (iii) Streptococcus positively correlated with liver fat area. (iv) Cecal acetate had direct negative correlation with liver fat area. Considering these relations comprehensively, acetate produced by Bifidobacterium may be a key mediator in ALD prevention; it inhibited growth of potential pathobiont Streptococcus and also directly regulated liver lipid metabolism reaching through portal vein. This study demonstrated that regularly intake of PHGG may be effective in reducing the risk of alcoholic fatty liver via gut–liver axis. [ABSTRACT FROM AUTHOR]

This study aims to investigate the alterations in serum bile acid profiles among individuals with fatty liver (including non-alcoholic fatty liver (NAFL) and alcoholic fatty liver (AFL) and evaluate their clinical significance when combined with liver enzyme levels. Methods: A cohort of 110 individuals with fatty liver (including non-alcoholic fatty liver 58 individuals and alcoholic fatty liver 52 individuals) was selected from the Department of Gastroenterology at Wenzhou People's Hospital between January 2021 and December 2022, while a control group of 66 healthy individuals was recruited from the hospital's health examination center during the same period. Clinical data and blood samples were collected from all participants. Serum bile acid profiles were quantified using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). Statistical analysis was conducted in conjunction with liver enzyme indicators. Results: In the NAFL group, GCA, TCA, and TCDCA levels were significantly elevated compared to the control group, with GCA (AUC 0.754, sensitivity 0.707, specificity 0.712), TCA (AUC 0.770, sensitivity 0.724, specificity 0.712), and TCDCA (AUC 0.782, sensitivity 0.810, specificity 0.652) showing strong diagnostic value. In the AFL group, TCDCA, TCA, GCA, TUDCA, and GUDCA were significantly elevated, with AUC values ranging from 0.848 to 0.912. Among these, TUDCA had the highest sensitivity (0.885) and specificity (0.773) for AFL diagnosis. TUDCA (sensitivity 0.615, specificity 0.897) was the key bile acid distinguishing AFL from NAFL, with an optimal cut-off of 36.33 nmol/L. These bile acids show significant diagnostic potential for differentiating NAFL and AFL. Conclusion: The bile acid profiles in both NAFL and AFL patients show changes, which hold potential clinical significance and may serve as serum biomarkers to differentiate NAFL from AFL. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the effects of niacin combined with B. animalis F1-7 on the improvement of alcoholic fatty liver disease (AFLD) in mice and its potential regulatory mechanism. Methods: A total of 75 8-week-old male C57BL/6N mice were acclimated for one week and randomly divided into five groups: control group, alcohol model group (AFLD), niacin intervention group (NA), B. animalis F1-7 intervention group (F1-7), and niacin combined with B. animalis F1-7 intervention group (NF). The experiment lasted for 8 weeks. Results: The results showed that all intervention groups could effectively reduce the serum lipid levels and inflammatory response of mice induced by alcohol to varying degrees. The immunofluorescence analysis showed that the GPR109A in the liver and intestine of the NF group was significantly enhanced compared with the other groups. Niacin combined with B. animalis F1-7 better restored the gut microbiota. Meanwhile, each intervention group could increase their levels of SCFAs. Among them, the combination group increased the levels of acetic acid and butyric acid more significantly than the other two groups. The Spearman's correlation analysis of gut microbiota and SCFAs showed that Norank_f_Eubacterium_coprostanoligenes_group, Allobaculum, and Akkermansia were positively correlated with changes in SCFAs, while Coriobacteriaceae_UCG-002, Romboutsia, and Clostridium_sensu_stricro_1 were negatively correlated. Conclusions: Niacin combined with B. animalis F1-7 better regulated the gut microbial balance and increased the SCFAs in mice with alcoholic steatohepatitis. The mechanism was related to the activation of the target GPR109A, which regulates the key proteins involved in lipid synthesis and β-oxidation to improve lipid metabolic disorders. [ABSTRACT FROM AUTHOR]

Background : Steatotic liver disease (SLD) encompasses metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-associated liver disease (AALD) at extremes as well as an overlap group termed MASLD with increased alcohol intake (MetALD). The Alcoholic Liver Disease/Nonalcoholic Fatty Liver Disease Index (ANI) was proposed to differentiate ALD from nonalcoholic fatty liver disease (NAFLD). We analysed the performance of the ANI in differentiating within the SLD spectrum. Methods : In a cross-sectional study at a tertiary care center, 202 adults (>18 years) who were prospectively diagnosed with SLD defined by magnetic resonance imaging-proton density fat fraction >6.4% were enrolled. Alcohol consumption (AC) was recorded according to thresholds for significant AC: 140-350 g/week (or 20-50 g/day) for females and 210-420 g/week (or 30-60 g/day) for males. The ANI was calculated, and area under the receiver operating characteristic curve (AUROC) was generated. Results : Of 202 patients (47 years [interquartile range, IQR, 38 to 55], 23.75% females, 77% obese, 42.1% with diabetes, 38.1% hypertensive, 28.7% statin use), 40.5% were ever-alcohol consumers; 120 (59%), 50 (24.7%), and 32 (15.8%) were MASLD (ANI, -3.7 [IQR, -7 to -1.6]; MetALD, - 1.45 [IQR, -2.4 to 0.28]; and AALD, 0.71 [IQR, -1.3 to 4.8], respectively; P-1.49), respectively. The ANI outperformed aspartate transaminase/alanine transaminase (AST/ALT) ratio (AUROC=0.75 [IQR, 0.69 to 0.81]) and gamma glutamyl transpeptidase (GGT) (AUROC=0.74 [IQR, 0.67 to 0.80]). Addition of GGT did not improve model performance (AUCdiff=0.004; P=0.33). Conclusion : AC is common in MASLD. The ANI distinguishes MASLD and AALD, with individual cut-offs within the intermediate zone indicating MetALD. ANI also outperforms AST/ALT ratio or GGT.

Background: Steatotic liver disease (SLD) encompasses metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-associated liver disease (AALD) at extremes as well as an overlap group termed MASLD with increased alcohol intake (MetALD). The Alcoholic Liver Disease/Nonalcoholic Fatty Liver Disease Index (ANI) was proposed to differentiate ALD from nonalcoholic fatty liver disease (NAFLD). We analysed the performance of the ANI in differentiating within the SLD spectrum. Methods: In a cross-sectional study at a tertiary care center, 202 adults (>18 years) who were prospectively diagnosed with SLD defined by magnetic resonance imaging-proton density fat fraction >6.4% were enrolled. Alcohol consumption (AC) was recorded according to thresholds for significant AC: 140-350 g/week (or 20-50 g/day) for females and 210-420 g/week (or 30-60 g/day) for males. The ANI was calculated, and area under the receiver operating characteristic curve (AUROC) was generated. Results: Of 202 patients (47 years [interquartile range, IQR, 38 to 55], 23.75% females, 77% obese, 42.1% with diabetes, 38.1% hypertensive, 28.7% statin use), 40.5% were ever-alcohol consumers; 120 (59%), 50 (24.7%), and 32 (15.8%) were MASLD (ANI, -3.7 [IQR, -7 to -1.6]; MetALD, - 1.45 [IQR, -2.4 to 0.28]; and AALD, 0.71 [IQR, -1.3 to 4.8], respectively; P<0.05 for all). The AUROC of the ANI for MASLD and AALD was 0.79 (IQR, 0.72 to 0.84; cut-off <-3.5) and 0.80 (IQR, 0.74 to 0.86; cut-off >-1.49), respectively. The ANI outperformed aspartate transaminase/alanine transaminase (AST/ALT) ratio (AUROC=0.75 [IQR, 0.69 to 0.81]) and gamma glutamyl transpeptidase (GGT) (AUROC=0.74 [IQR, 0.67 to 0.80]). Addition of GGT did not improve model performance (AUCdiff=0.004; P=0.33). Conclusion: AC is common in MASLD. The ANI distinguishes MASLD and AALD, with individual cut-offs within the intermediate zone indicating MetALD. ANI also outperforms AST/ALT ratio or GGT. [ABSTRACT FROM AUTHOR]

Background & Aims: Nonalcoholic fatty liver disease (NAFLD) is typically first suspected when the results of liver function tests, measured as part of routine testing, are abnormal. Most often observed biochemical pattern in hepatic steatosis due to NAFLD is of increased levels of transaminases, with alanine aminotransferase (ALT) levels exceeding those of aspartate aminotransferase (AST). This classical pattern is particularly useful in differentiating between hepatic steatosis from NAFLD.The pathophysiology of non-metabolic complication like atherosclerosis and cardiovascular disease (CVD) depends vastly on fatty acids (lipid) transportation and Deposition. AIM Estimation of the AST: ALT, Albumin: Globulin, and TG: HDL ratios, along with their comparison among the Alcoholic and Non-alcoholic fatty liver disease patient. Materials & Methods: A prospective observational cohort study was conducted in the department of Biochemistry at GBCM & KKBM Subharti hospital, Jhajra, Dehradun after obtaining the ethical clearance from the institutional ethical committee (IEC) with registration no GBCM/IEC/2023/07-03 dated 25/07/2023. Cases comprised of 120 Ultrasonographically confirmed fatty liver patients by Random sampling method. 5ml blood sample was collected in the serum separation test tube (SST) and results were analysed using SPSS v.20. and statistical p-value of

Alcohol-associated liver disease (ALD) remains a major and increasingly pressing concern in hepatology. ALD includes spectrum of conditions, each with unique diagnostic and therapeutic challenges. Excessive alcohol intake is a leading preventable cause of physical harm, including ALD. The pathogenesis of ALD involves oxidative stress, inflammation, and lipid metabolism disruptions, with genetic predispositions playing a major role. ALD progresses from hepatic steatosis to steatohepatitis, and finally liver cirrhosis, which is marked by severe fibrosis and impaired liver function. Advanced ALD stages, particularly alcoholic hepatitis and liver cirrhosis, are characterized by high mortality rates. Management of ALD primarily involves strict abstinence from alcohol, which can reverse early-stage disease or halt progression. Nutritional support, vitamin supplementation, and symptomatic treatment are also essential. Liver transplantation is the only definitive treatment for alcoholic liver cirrhosis, but it is difficult for patients with a history of alcohol abuse to qualify for the procedure. Epidemiological data indicate a growing burden of ALD, especially among younger populations, exacerbated by increased alcohol consumption trends and the COVID-19 pandemic's influence on drinking behaviors. Despite ALD's significant impact, current therapies are limited, highlighting the need for innovative treatments and comprehensive patient management strategies. Individualized care, enhanced epidemiological research, and new therapeutic approaches are crucial to improving outcomes for ALD patients. [ABSTRACT FROM AUTHOR]

The liver is critical in alcohol metabolism, and excessive consumption heightens the risk of hepatic damage, potentially escalating to hepatitis and cirrhosis. Jiuzao, a by-product of Baijiu production, contains a rich concentration of naturally active polysaccharides known for their antioxidative properties. This study investigated the influence of Laowuzeng Jiuzao polysaccharide (LJP) on the development of ethanol-induced alcoholic fatty liver. Zebrafish larvae served as the model organisms for examining the LJPs hepatic impact via liver phenotypic and biochemical assays. Additionally, this study evaluated the LJPs effects on gene expression associated with alcoholic fatty liver and the composition of the intestinal microbiota through transcriptomic and 16 S rRNA gene sequencing analyses, respectively. Our findings revealed that LJP markedly mitigated morphological liver damage and reduced oxidative stress and lipid peroxidation in larvae. Transcriptome data indicated that LJP ameliorated hepatic fat accumulation and liver injury by enhancing gene expression involved in alcohol and lipid metabolism. Furthermore, LJP modulated the development of alcoholic fatty liver by altering the prevalence of intestinal Actinobacteriota and Firmicutes, specifically augmenting Acinetobacter while diminishing Chryseobacterium levels. Ultimately, LJP mitigated alcohol-induced hepatic injury by modulating gene expression related to ethanol metabolism, lipid metabolism, and inflammation and by orchestrating alterations in the intestinal microbiota. [ABSTRACT FROM AUTHOR]

Alcoholic liver disease (ALD) is a global liver disease that manifests in a variety of forms, including alcoholic hepatitis, liver inflammation, fatty liver, and liver cirrhosis. One of the early stages of ALD is alcoholic fatty liver (AFL) disease, which is primarily characterized by the accumulation of lipids and inflammation in hepatocytes. Guanylate binding protein 5 (GBP5) has been investigated for its involvement in disease progression. The regulatory effects of GBP5 on the progression of AFL disease are still not well understood. This study aims to investigate the impact of GBP5 on AFL progression and its underlying mechanism of action. To achieve this, gene expression was evaluated using western blot and reverse transcription quantitative polymerase chain reaction (RT-qPCR) methods. Lipid accumulation was confirmed using the Oil Red O staining assay, while the levels of Triglyceride (TG), aspartate aminotransferases (AST), and alanine aminotransferases (ALT) were measured using commercial kits. The levels of inflammatory cytokines were assessed using enzyme-linked immuno sorbent assay (ELISA) assay. Finally, cell apoptosis was evaluated using flow cytometry. Cell apoptosis was evaluated through flow cytometry. Our work demonstrated that GBP5 expression was up-regulated in the Ethyl Alcohol (EtOH) group. Additionally, lipid accumulation was increased after EtOH inducement, but this change was attenuated by silencing GBP5. Silencing of GBP5 reduced EtOH-mediated inflammation and cell apoptosis. Finally, it was discovered that knockdown of GBP5 retarded the EtOH-stimulated nuclear factor kappa-B (NF-κB) pathway. Knockdown of GBP5 alleviated lipid accumulation and inflammation in AFL through inhibition of NF-κB pathway. This finding suggested that GBP5 may be a useful bio-target for AFL treatment.

Alcohol effect hepatic lipid metabolism through various mechanisms, leading synergistically to an accumulation of fatty acids (FA) and triglycerides. Obesity, as well as dietary fat (saturated fatty acids (FA) versus poly-unsaturated fatty acids (PUFA)) may modulate the hepatic fat. Alcohol inhibits adenosine monophosphate activated kinase (AMPK). AMPK activates peroxisome proliferator activated receptor a (PPARα) and leads to a decreased activation of sterol regulatory element binding protein 1c (SRABP1c). The inhibition of AMPK, and thus of PPARα, results in an inhibition of FA oxidation. This ß-oxidation is further reduced due to mitochondrial damage induced through cytochrome P4502E1 (CYP2E1)-driven oxidative stress. Furthermore, the synthesis of FAs is stimulated through an activation of SHREP1. In addition, alcohol consumption leads to a reduced production of adiponectin in adipocytes due to oxidative stress and to an increased mobilization of FAs from adipose tissue and from the gut as chylomicrons. On the other side, the secretion of FAs via very-low-density lipoproteins (VLDL) from the liver is inhibited by alcohol. Alcohol also affects signal pathways such as early growth response 1 (Egr-1) associated with the expression of tumour necrosis factor α (TNF α), and the mammalian target of rapamycin (mTOR) a key regulator of autophagy. Both have influence the pathogenesis of alcoholic fatty liver. Alcohol-induced gut dysbiosis contributes to the severity of ALD by increasing the metabolism of ethanol in the gut and promoting intestinal dysfunction. Moreover, pathogen-associated molecular patterns (PAMPS) via specific Toll-like receptor (TLR) bacterial overgrowth leads to the translocation of bacteria. Endotoxins and toxic ethanol metabolites enter the enterohepatic circulation, reaching the liver and inducing the activation of the nuclear factor kappa-B (NFκB) pathway. Pro-inflammatory cytokines released in the process contribute to inflammation and fibrosis. In addition, cellular apoptosis is inhibited in favour of necrosis. [ABSTRACT FROM AUTHOR]

The effects of superfine grinding (SG) and microwave treatment (MT) on the structure and physicochemical properties of artichoke soluble dietary fiber (ASDF) and its protective effects on mice with alcoholic fatty liver (AFL) were studied. We compared the changes in structural characteristics and physicochemical properties of ASDF, SG-ASDF (ASDF treated by SG), MT-ASDF (ASDF treated by MT), and CM-ASDF (ASDF treated by SG and MT). Moreover, we evaluated the effects of the obtained ASDF on the growth characteristics, blood lipid levels, and liver of mice with AFL. Our results of the study showed that CM-ASDF had a more concentrated and uniform particle size, a higher extraction rate of ASDF and significantly improved water-holding capacity (WHC), oil-holding capacity (OHC) and water swelling capacity (WSC) of ASDF (p

Objective To analyze the effect of exenatide combined with polyene phosphatidyl choline on alcoholic fatty liver disease and their effect on serum high mobility group protein B1（HMGB1）and adiponectin （APN）levels. Methods A total of 108 patients with alcoholic fatty liver disease admitted to our hospital from January 2020 to January 2022 were divided into observation group and control group by random number table method, with 54 cases in each group. The control group was treated with polyene phosphatidyl choline, and the observation group was treated with exenatide on the basis of control group. The therapeutic effect and serum levels of HMGB1 and APN in 2 groups were observed and compared between the two groups. Results After 3 months of treatment, the clinical symptoms of both groups were significantly improved and the clinical symptoms disappeared faster. The total clinical effective rate of the observation group was significantly higher than that of the control group （96.30% vs. 83.33%, P<0.05）. There were no significant differences in the serum ALT, AST, TC, TG and TBil between the two groups before treatment（all P>0.05）. After treatment, the all indexes of the two groups were significantly decreased, and those of the observation group were lower than of the control group（P<0.01）. There was no significant difference in the serum HMGB1 and APN levels between the two groups before treatment. After treatment, the serum HMGB1 level in the two groups was significantly decreased（P<0.001）, and the serum HMGB1 level in the observation group was lower than that in the control group（P<0.05）. After treatment, the serum APN levels of both groups were significantly increased（P<0.001）, and the level of observation group was significantly higher than of the control group（P<0.05）. There was no significant difference in the adverse reactions between the two groups（P>0.05）. Conclusion Exenatide combined with polyene phosphatidyl choline can improve the therapeutic effect of alcoholic fatty liver disease, reduce serum HMGB1 level and increase serum APN level safely. [ABSTRACT FROM AUTHOR]

The tumor suppressor p53 is critical for tumor suppression, but the regulatory role of p53 in alcohol‐induced fatty liver remains unclear. Here, we show a role for p53 in regulating ethanol metabolism via acetaldehyde dehydrogenase 2 (ALDH2), a key enzyme responsible for the oxidization of alcohol. By repressing ethanol oxidization, p53 suppresses intracellular levels of acetyl‐CoA and histone acetylation, leading to the inhibition of the stearoyl‐CoA desaturase‐1 (SCD1) gene expression. Mechanistically, p53 directly binds to ALDH2 and prevents the formation of its active tetramer and indirectly limits the production of pyruvate that promotes the activity of ALDH2. Notably, p53‐deficient mice exhibit increased lipid accumulation, which can be reversed by ALDH2 depletion. Moreover, liver‐specific knockdown of SCD1 alleviates ethanol‐induced hepatic steatosis caused by p53 loss. By contrast, overexpression of SCD1 in liver promotes ethanol‐induced fatty liver development in wild‐type mice, while it has a mild effect on p53−/− or ALDH2−/− mice. Overall, our findings reveal a previously unrecognized function of p53 in alcohol‐induced fatty liver and uncover pyruvate as a natural regulator of ALDH2. Synopsis: The tumor suppressor p53 regulates diverse metabolic processes, but its contribution to the development of alcohol‐induced fatty liver remains unclear. This study shows that p53 regulates ethanol metabolism by inhibiting acetaldehyde dehydrogenase 2 (ALDH2). p53 directly binds ALDH2 and inhibits ethanol oxidation.Pyruvate also binds ALDH2 and enhances its activity.p53 suppresses the progression of alcoholic fatty liver disease in an ALDH2‐dependent manner.ALDH2 contributes to the p53‐dependent regulation of histone acetylation and lipid metabolism. [ABSTRACT FROM AUTHOR]

Mitochondria are generally considered the powerhouse of the cell, a small subcellular organelle that produces most of the cellular energy in the form of adenosine triphosphate (ATP). In addition, mitochondria are involved in various biological functions, such as biosynthesis, lipid metabolism, oxidative phosphorylation, cell signal transduction, and apoptosis. Mitochondrial dysfunction is manifested in different aspects, like increased mitochondrial reactive oxygen species (ROS), mitochondrial DNA (mtDNA) damage, adenosine triphosphate (ATP) synthesis disorder, abnormal mitophagy, as well as changes in mitochondrial morphology and structure. Mitochondrial dysfunction is related to the occurrence and development of various chronic liver diseases, including hepatocellular carcinoma (HCC), viral hepatitis, drug-induced liver injury (DILI), alcoholic fatty liver (AFL), and non-alcoholic fatty liver (NAFL). In this review, we summarize and discuss the role and mechanisms of mitochondrial dysfunction in chronic liver disease, focusing on and discussing some of the latest studies on mitochondria and chronic liver disease.

The liver is critical in alcohol metabolism, and excessive consumption heightens the risk of hepatic damage, potentially escalating to hepatitis and cirrhosis. Jiuzao, a by-product of Baijiu production, contains a rich concentration of naturally active polysaccharides known for their antioxidative properties. This study investigated the influence of Laowuzeng Jiuzao polysaccharide (LJP) on the development of ethanol-induced alcoholic fatty liver. Zebrafish larvae served as the model organisms for examining the LJPs hepatic impact via liver phenotypic and biochemical assays. Additionally, this study evaluated the LJPs effects on gene expression associated with alcoholic fatty liver and the composition of the intestinal microbiota through transcriptomic and 16 S rRNA gene sequencing analyses, respectively. Our findings revealed that LJP markedly mitigated morphological liver damage and reduced oxidative stress and lipid peroxidation in larvae. Transcriptome data indicated that LJP ameliorated hepatic fat accumulation and liver injury by enhancing gene expression involved in alcohol and lipid metabolism. Furthermore, LJP modulated the development of alcoholic fatty liver by altering the prevalence of intestinal Actinobacteriota and Firmicutes, specifically augmenting Acinetobacter while diminishing Chryseobacterium levels. Ultimately, LJP mitigated alcohol-induced hepatic injury by modulating gene expression related to ethanol metabolism, lipid metabolism, and inflammation and by orchestrating alterations in the intestinal microbiota.

Objective: To investigate the effect of Growth and Differentiation Factor 15 ( GDF15) on alcoholic fatty liver (AFL). Methods: A model of mouse with alcoholic fatty liver disease was constructed with liquor, and then the control group and the model group were injected with AAV8-GDF15 molecules overexpressing the liver in the tail vein, and the mice were divided into four groups-normal + tail vein injection control AAV8-NC group (Con+AAV8-NC), model (alcohol) + tail vein injection AAV8 control virus group (AFL+AAV8-NC), normal + tail vein injection overexpressed AAV8-Gdf15 group (Con+ AAV8-Gdf15), alcohol + tail vein injection overexpressed AAV8-Gdf15 group (AFL+AAV8-Gdf15). By measuring body weight, fasting blood glucose, Intraperitoneal glucose tolerance test (IPGTT), insulin release test (ITT), and using test kits for their serum lipids, liver fats, alanine transaminase (ALT),Determination of aspartate transaminase (AST); liver biopsy sections were detected by hematoxylin-eosinstaining (HE) staining to detect structural abnormalities; The effect of over expression of GDF15 on alcoholic fatty liver was observed via q-PCR detecting of lipid metabolism-related molecular RNA levels, etc. Results: Compared with the Con+AAV8-NC group, weight loss was observed in group AFL+AAV8-NC. The weight loss in the AFL+AAV8-Gdf15 group was reduced compared to AFL+AAV8-NC after over expression of GDF15. Compared with the Con+AAV8-NC group, the fasting blood glucose in the AFL+AAV8-NC group increased, and the sugar tolerance and insulin resistance decreased. After overexpression of GDF15, the AFL+AAV8-Gdf15 group decreased significantly in fasting blood glucose and increased glucose tolerance and insulin resistance compared with AFL+AAV8-NC. The AFL+AAV8-NC group was significantly elevated compared with the Con+AAV8-NC group, and the lipids of the AFL+AAV8-Gdf15 group decreased significantly compared with those in the AFL+AAV8-NC group after overexpression of GDF15. Compared with the Con+AAV8-NC group, the liver weight of the AFL+AAV8-NC group increased, the degree of liver function damage was more severe, and the fat content of the liver increased. After the expression of GDF15, the liver weight, degree of damage and fat content of the liver were significantly reduced in group AFL+AV8-Gdf15 compared with AFL+AAV8-NC group. Conclusion: Alcoholic fatty liver disease increases the expression of GDF15, and increased expression of GDF15 will improve the damage and metabolic abnormalities of alcoholic fatty liver. [ABSTRACT FROM AUTHOR]

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Background: At present, the incidence of alcoholic fatty liver disease (AFLD) is increasing year by year, and numerous studies have confirmed that liver diseases are closely related to intestinal flora. Seabuckthorn and Astragalus membranaceus, as traditional Chinese medicine (TCM) with the homology of medicine and food, have good liver protection, and their polysaccharides can regulate the intestinal flora. Here, we studied the effects of HRP, APS and the combination of the two polysaccharides on the intestinal flora of AFLD mice, which provided scientific basis for the treatment of AFLD with the two polysaccharides. Materials and methods: Thirty Kunming (KM) mice were randomly divided into the control group (Con), the model group (Mod), the HRP treatment group (HRP), the APS treatment group (APS), and HRP+APS treatment group (HRP+APS), with six mice in each group. The AFLD model was constructed by continuous intragastric administration of 42% vol Niulanshan ethanol solution for 28 days, and the mice in each polysaccharide group were given corresponding drugs. The levels of AST, ALT, TC and TG in serum of mice were measured. 16S rRNA amplicon sequencing technique was used to determine the diversity and richness of intestinal flora, and the relative abundance of intestinal flora at phylum level and genus level of the mice in each group. Results: HRP, APS and HRP+APS could reduce the serum levels of AST, ALT, TC and TG in mice. In addition, HRP, APS and HRP + APS restored the diversity, relative abundance and community structure of intestinal mucosa bacteria in AFLD mice to a certain extent. Specifically, HRP, APS and HRP+APS remarkably decreased the ratio of Firmicutes to Bacteroidetes, and ultimately increased the abundance of beneficial bacteria and reduced the abundance of pathogenic bacteria. Conclusion: HRP, APS, and HRP+APS can improve the intestinal microecology of AFLD model mice, alleviate liver injury, and maintain normal intestinal function in different degrees. [ABSTRACT FROM AUTHOR]

Lipid metabolism disorders are the primary causes for the occurrence and progression of various liver diseases, including non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) caused by a high-fat diet and ethanol. AMPK signaling pathway plays an important role in ameliorating lipid metabolism disorders. Progressive research has clarified that AMPK signal axes are involved in the prevention and reduction of liver injury. Upregulation of AMK can alleviate FLD in mice induced by alcohol or insulin resistance, type 2 diabetes, and obesity, and most natural AMPK agonists can regulate lipid metabolism, inflammation, and oxidative stress in hepatocytes, consequently regulating FLD in mice. In NAFLD and AFLD, increasing the activity of AMPK can inhibit the synthesis of fatty acids and cholesterol by down-regulating the expression of adipogenesis gene (FAS, SREBP-1c, ACC and HMGCR); Simultaneously, by increasing the expression of fatty acid oxidation and lipid decomposition genes (CPT1, PGC1, and HSL, ATGL) involved in fatty acid oxidation and lipid decomposition, the body's natural lipid balance can be maintained. At present, some AMPK activators are thought to be beneficial during therapeutic treatment. Therefore, activation of AMPK signaling pathway is a potential therapeutic target for disorders of the liver. We summarized the most recent research on the role of the AMPK pathway in FLD in this review. Simultaneously, we performed a detailed description of each signaling axis of the AMPK pathway, as well as a discussion of its mechanism of action and therapeutic significance. [ABSTRACT FROM AUTHOR]