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Objective: This study investigated copper (Cu) status in relation to abdominal obesity indices and liver function in patients with non-alcoholic fatty liver disease (NAFLD). This case-control study was carried out on 80 overweight/obese patients with NAFLD and 80 apparently healthy age, sex, and body mass index (BMI)-matched controls. A validated and reliable 168-item semi-quantitative food frequency questionnaire was completed for each subject and fasting serum levels of liver aminotransferases, ferritin, Cu and ceruloplasmin were assessed. Results: Mean intakes of energy and carbophydrate were significantly lower in patients with NAFLD than the control group while mean protein intake was highre (p < 0.05). Although mean Cu intake was greater in cases than controls, low dietary intake of Cu was found in 7.5% and 32.5% of the cases and controls, respectively. Apart from serum levels of liver aminotransferases (p < 0.001) and ferritin (p = 0.010), no significant differences were found in serum levels of Cu and ceruloplasmin. Serum and dietary Cu were positively correlated with obesity indices and serum ceruloplasmin was correlated with waist to height ratio and ferritin only in cases (p < 0.05). Low Cu intake (< 0.95 mg/day) was more likely to increase the odds of NAFLD (p for trend = 0.002), after adjusting for potential confounders. [ABSTRACT FROM AUTHOR]

Background: Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease in human history and it is expected to surpass other causes of liver disease mortality by 2030. Therefore, finding an alternative way to diagnose steatosis in the early stage when imaging modalities are not available is crucial. This study decided to validate the optimal cut-off points and the sensitivity and specificity of the Fatty Liver Index (FLI) based on the Iranian population compared to ultrasonography. Methods: The data of 367 individuals, 108 males and 259 females over 35, were analyzed. Hepatic steatosis was identified by ultrasound. FLI was determined from waist circumference, gamma-glutamyl transferase, triglyceride, and body mass index data. The receiver operating characteristic curve (ROC) was used to determine the best FLI index cut point for diagnosing nonalcoholic fatty liver. The sensitivity and specificity indices were calculated for the determined cut point. Results: The AUC of the FLI index in diagnosing NAFLD in the total population was 0.733 (95% CI: 0.68–0.77, specificity = 0.6705, sensitivity = 0.7320) with the optimal COP of 40.6. There was a statistically significant association between non-alcoholic liver disease and FLI-based ultrasound (p < 0.0001). Furthermore, the sex-specific optimal COPs of FLI was 33.4, specificity = 0.6071, sensitivity = 0.8462 in men vs. 27.8, sensitivity = 0.8233, specificity = 0.7655 in women. Conclusion: FLI is a reliable tool for identifying individuals with NAFLD. It has the potential to aid in detecting and managing this condition in large-scale populations while other methods are not available. We also determine an optimal COP of 40.6 with sensitivity and specificity of 73.20% and 67.05% in the general population, respectively. [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 and Objectives The aim of this study was to investigate the Effect of eight weeks of selected Pilates training on lipid profile, fasting blood sugar, blood pressure and fat percentage of women with non-alcoholic fatty liver disease in Ahvaz city. Subjects and Methods In this semi-experimental study, 20 women with non-alcoholic fatty liver were randomly simple divided into two groups: Pilates training (N=10) with an average age of 42.2±8.68 years and an average weight of 79.8±4.7 kg, and control group (N=10) with an average age of 40.1±8.97 years and an average weight of 80.4±5.10 kg. The training group did Pilates training for 60 minutes three days a week for eight weeks. The control group did not participate in any sports activities. Following data collection, independent samples t-test and analysis of covariance were run and the data were analyzed using SPSS26 software at a significance level of P<0.05. Results The results of this study showed that eight weeks of selected Pilates training increased HDL levels and as well as significantly decreased the levels of TC, TG, LDL, VLDL, FBS and indicators blood pressure (systolic and diastolic) and body fat percentage in the Pilates training group compared to the control group (P<0.05). Conclusion According to the results of this research Pilates training can be used to reduce the levels of TC, TG, LDL,VLDL, FBS, blood pressure (systolic and diastolic) and fat percentage and increase HDL levels [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of liver dysfunction, and its prevalence has increased significantly. Based on the research conducted, physical activity while increasing the expression of proteins such as peroxisome proliferator-activated receptor alpha (PPARa) with increasing energy consumption causes a decrease in the accumulation of fat in the liver and thus affects NAFLD. The goal of the present study is to identify critical genes and key pathways associated with NAFLD, and to analyze the gene networks involved in this disease, alongside the impact of exercise on these pathways. Furthermore, bioinformatics analyses have been conducted to clarify the interactions between these genes and pathways. We determined the pathways by using the analyzed transcriptional data and hub genes involved in NAFLD-related pathways. Network cluster analysis confirmed the result of Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The discovered genes are fatty acid synthase (FASN), acyl-CoA oxidase 1 (ACOX1), Sterol regulatory element-binding transcription factor 1 (SREBF1-c), PPARa, which are involved in the processes of pathogenesis or resistance to NAFLD. The results of this study provide a list of hub genes, important pathways and new insights for the future development of NAFLD treatment and elucidate the underlying mechanism of liver response to exercise. [ABSTRACT FROM AUTHOR]

Abstract Objective This study investigated copper (Cu) status in relation to abdominal obesity indices and liver function in patients with non-alcoholic fatty liver disease (NAFLD). This case-control study was carried out on 80 overweight/obese patients with NAFLD and 80 apparently healthy age, sex, and body mass index (BMI)-matched controls. A validated and reliable 168-item semi-quantitative food frequency questionnaire was completed for each subject and fasting serum levels of liver aminotransferases, ferritin, Cu and ceruloplasmin were assessed. Results Mean intakes of energy and carbophydrate were significantly lower in patients with NAFLD than the control group while mean protein intake was highre (p

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease in human history and it is expected to surpass other causes of liver disease mortality by 2030. Therefore, finding an alternative way to diagnose steatosis in the early stage when imaging modalities are not available is crucial. This study decided to validate the optimal cut-off points and the sensitivity and specificity of the Fatty Liver Index (FLI) based on the Iranian population compared to ultrasonography. Methods The data of 367 individuals, 108 males and 259 females over 35, were analyzed. Hepatic steatosis was identified by ultrasound. FLI was determined from waist circumference, gamma-glutamyl transferase, triglyceride, and body mass index data. The receiver operating characteristic curve (ROC) was used to determine the best FLI index cut point for diagnosing nonalcoholic fatty liver. The sensitivity and specificity indices were calculated for the determined cut point. Results The AUC of the FLI index in diagnosing NAFLD in the total population was 0.733 (95% CI: 0.68–0.77, specificity = 0.6705, sensitivity = 0.7320) with the optimal COP of 40.6. There was a statistically significant association between non-alcoholic liver disease and FLI-based ultrasound (p

Non-alcoholic fatty liver disease (NAFLD) is one abnormal buildup of fat within the liver, independent of excessive alcohol intake. In type 2 diabetes, the presence of NAFLD can exacerbate chronic kidney diseases and mortality in patients. Hepatocyte nuclear factor 1 homeobox A (HNF1A) predominantly expressed in the liver, owns one crucial role in liver development, function and tumorigenesis. However, the precise regulatory role of HNF1A on the progression of type 2 diabetes combined with NAFLD keep dimness. This investigation uncovered that HNF1A levels, both in protein and mRNA expressions, were elevated in high-fat diet plus hyperglycemia (HFG) mice. Furthermore, liver steatosis was strengthened in the HFG group, which was mitigated following the HNF1A inhibition. Knockdown of HNF1A ameliorated glucose and lipid metabolism disorders in HFG mice. Lastly, the study observed an stimulation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway in HFG mice, but this change was neutralized uponHNF1A silencing. In conclusion, knockdown of HNF1A improved type 2 diabetes combined with NAFLD, as well as disorders in glucose and lipid metabolism, and retarded the PI3K/AKT/mTOR signaling pathway. These finding demonstrated that HNF1A may be one serviceable target for ameliorating type 2 diabetes combined with NAFLD.

Background: Hypothyroidism can play an important role in the development of non-alcoholic fatty liver disease (NAFLD). This study compared the thyroid function tests in overweight and obese children and adolescents with and without NAFLD. Methods: This case-control study was conducted on 100 children and adolescents aged 4-18 years who referred to the endocrinology clinic of Amirkola Children's Hospital, Babol, Iran in 2021. 42 obese and overweight children with NAFLD were considered as case group and 56 persons without NAFLD as control group. They were selected after physical examination and body mass index (BMI) assessment. Then, TSH, T4, FBS, lipid profile, 25(OH) vit D3 (VD), AST and ALT levels were measured. Abdominal ultrasound was performed to survey fatty liver. T-test and Chi-score were used for analysis and p< 0.05 was considered significant. Results: The mean age in both group was 11.63±2.55 and 10.07±2.61 years, respectively (P=0.004). Hypothyroidism was not seen in the groups. Two groups in terms of mean TSH (P=0.92), T4 (P=0.87), FBS (P=0.33), cholesterol (P=0.44), LDL (P=0.35), VD (P=0.07) had no significant difference. However, difference was found between the two groups in terms of the mean level of AST (P=0.003), ALT (P=0.001), TG (P=0.02), HDL (P=0.01) and BMI (P

Background: Hypothyroidism can play an important role in the development of nonalcoholic fatty liver disease (NAFLD). This study compared the thyroid function tests in overweight and obese children and adolescents with and without NAFLD. Methods: This case-control study was conducted on 100 children and adolescents aged 4-18 years who referred to the endocrinology clinic of Amirkola Children's Hospital, Babol, Iran in 2021. 42 obese and overweight children with NAFLD were considered as case group and 56 persons without NAFLD as control group. They were selected after physical examination and body mass index (BMI) assessment. Then, TSH, T4, FBS, lipid profile, 25(OH) vit D3 (VD), AST and ALT levels were measured. Abdominal ultrasound was performed to survey fatty liver. T-test and Chi-score were used for analysis and p< 0.05 was considered significant. Results: The mean age in both group was 11.63±2.55 and 10.07±2.61 years, respectively (P=0.004). Hypothyroidism was not seen in the groups. Two groups in terms of mean TSH (P=0.92), T4 (P=0.87), FBS (P=0.33), cholesterol (P=0.44), LDL (P=0.35), VD (P=0.07) had no significant difference. However, difference was found between the two groups in terms of the mean level of AST (P=0.003), ALT (P=0.001), TG (P=0.02), HDL (P=0.01) and BMI (P=0.001). Conclusion: This study showed that the mean level of thyroid hormones in both groups did not have significant difference and hypothyroidism was not seen. Other studies with larger sample size and longer periods of time are suggested. [ABSTRACT FROM AUTHOR]

The objective was to assess the potential differential effects of human versus mouse growth hormone in vivo, given that human unlike mouse growth hormone can bind prolactin as well as the growth hormone receptor. To this end, a transgenic CD-1 mouse expressing human but not mouse growth hormone was generated, and the phenotypes of male mice fed with a regular chow or high-fat diet were assessed. Pancreas and epididymal white adipose tissue gene expression and/or related function were targeted as the pancreas responds to both prolactin and growth hormone receptor signaling, and catabolic effects like lipolytic activity are more directly attributable to growth hormone and growth hormone receptor signaling. The resulting human growth hormone-expressing mice are smaller than wildtype CD-1 mice, despite higher body fat and larger adipocytes, but both mouse types grow at the same rate with similar bone densities. Unlike wild-type mice, there was no significant delay in glucose clearance in human growth hormone-expressing mice when assessed at 8 versus 24 weeks on a high-fat diet. However, both mouse types showed signs of hepatic steatosis that correlated with elevated prolactin but not growth hormone RNA levels. The larger adipocytes in human growth hormone-expressing mice were associated with modified leptin (higher) and adiponectin (lower) RNA levels. Thus, while limited to observations in the male, the human growth hormone-expressing mice exhibit signs of growth hormone insufficiency and adipocyte dysfunction as well as an initial resistance to the negative effects of high-fat diet on glucose clearance. [ABSTRACT FROM AUTHOR]

BackgroundNon-alcoholic fatty liver disease (NAFLD) is a widespread liver condition associated with diabetes, metabolic syndrome, and cardiovascular diseases, yet public awareness remains low. Early detection of risk factors is crucial, but liver biopsy, the diagnostic gold standard, is invasive and costly. Non-invasive anthropometric indices provide a safer alternative. This study examines these indices to identify the most reliable predictor of NAFLD in adults.MethodsIn the present cross-sectional study, we used the Fasa Cohort Data, conducted on about 10,000 people, of whom 1,047 were diagnosed with NAFLD. NAFLD diagnosis in this study was confirmed by physicians based on medical history and ultrasonographic evaluations, ensuring accurate and reliable identification of cases. General, anthropometric, and dietary assessments were performed using interviews, tools, and valid questionnaires. Biochemical evaluation was also done. Waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), Body mass index (BMI), a body shape index (ABSI), body roundness index (BRI), and visceral fat index (VAI) were also calculated using these measurements and formulas. This study used descriptive tests, binary logistic regression, and ROC curve analysis.ResultsIn both crude and adjusted models, significant associations were found between WHR, WHtR, BMI, and VAI with NAFLD. ROC analysis revealed that WHtR and BMI were the most accurate predictors of NAFLD in both genders (WHtR: men AUC = 0.750, women AUC = 0.702; BMI: men AUC = 0.754, women AUC = 0.701). BRI showed significant accuracy, but WHR (men: AUC = 0.727, women: AUC = 0.640) and VAI (men: AUC = 0.621, women: AUC = 0.622) were less effective. ABSI demonstrated poor predictive power (men: AUC = 0.530, women: AUC = 0.505) and is not recommended for NAFLD prediction.ConclusionBased on the findings, BMI and WHtR emerge as the most practical and accessible indicators for early screening of NAFLD in both men and women, while ABSI shows minor effectiveness in identifying the disease.

A type of oligosaccharide named mulberry galacto-oligosaccharides (MGO), was isolated from mulberry with a galactose-only, weighs 987 Da and displays diverse biological properties. The objective of this work was to investigate the protective effects of MGO in non-alcoholic fatty liver disease (NAFLD) mice. The results showed that MGO can reduce the body weight and liver weight of NAFLD mice, and reduce the levels of NEFA, TG, TC and LDL-C in serum and liver as well as the activities of AST and ALT. Increase HDL-C content, SOD, and GSH activity in serum and improve pathological damage. MGO regulates the AMPK lipid metabolism pathway, upregulates the expression of ATGL, downregulates the expression of SREBP-1, inhibits lipogenesis, and promotes lipolysis. MGO alleviates liver function damage in NAFLD mice, improves blood lipids, liver metabolism, and increases the body’s antioxidant capacity, suggesting MGO potential as a dietary supplement and functional food to combat HFD-induced NAFLD.

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

This study aimed to systematically evaluate the efficacy of liraglutide in treating type 2 diabetes mellitus (T2DM) complicated with non-alcoholic fatty liver disease (NAFLD) by comparing liraglutide with placebo or other drugs (mainly insulin). The PubMed, Web of Science, and National Library of Medicine databases were systematically searched from their inception until December 1, 2023. A meta-analysis was performed using Stata 15.1 software. A total of 12 studies with 13 outcome measures were included. The meta-analysis results revealed that liraglutide significantly reduced body mass index (mean difference [MD] = –1.06, 95%CI: –1.41, –0.70, p < 0.001), triglycerides (MD = –0.35, 95%CI: –0.61, –0.09, p = 0.0009), visceral adipose tissue (MD = –21.06, 95%CI: –34.58, –7.55, p = 0.002), and subcutaneous adipose tissue (MD = –20.53, 95%CI: –29.15, –11.90, p < 0.001) levels in patients with T2DM and NAFLD. Of the 11 studies, 2 reported the occurrence of adverse reactions, which were primarily gastrointestinal. Compared with placebo and other drugs (e.g., insulin), liraglutide may improve glucose metabolism, lipid and liver function parameters, and visceral and subcutaneous fat in patients with T2DM and NAFLD, thus constituting an effective treatment for these patients.

Objective: This study aimed to assess the effect of sumac supplement in biochemical and anthropometric measurements in overweight or obese patients with non-alcoholic fatty liver disease.Materials and Methods: In this double-blind randomized controlled trial, 45 NAFLD patients were randomly divided into two groups. The intervention group received sumac capsules (3 g/day) with a balanced diet for 8 weeks, while the placebo group received placebo with a balanced diet. Anthropometric indices, lipid profile, fasting blood glucose, insulin, Homeostatic Model Assessment for Insulin Resistance, aspartate transaminase, alanine aminotransferase, high sensitivity C-reactive protein and malondialdehyde were measured at baseline and at the end of the study.Results: The results revealed a significant decrease in anthropometric indices (weight (p=0.001), body mass index (p=0.001), waist circumference (p=0.001), body fat mass (p=0.001), body fat percentage (p=0.001), visceral fat score (p=0.001), biochemical levels of total cholesterol (p=0.007), fasting blood sugar (p=0.006), insulin (p=0.004) and HOMA-IR (p=0.002)) after the intervention compared to the baseline. However, no significant difference was observed between the two groups concerning anthropometric and biochemical indices.Conclusion: In this study, no significant differences were observed between the two groups regarding anthropometric and biochemical indices. Thus, further studies with larger sample sizes are recommended to be conducted on the issue.

Objective: Considering the high prevalence of non-alcoholic fatty liver disease and its complications, this study aims to determine and compare the effect of nano-silymarin and silymarin on non-alcoholic fatty liver in rats.Materials and Methods: Rats were divided into 5 groups: Control, high-fat diet, high-fat diet and atorvastatin, high-fat diet and silymarin, and high-fat diet and nano-silymarin. After 12 weeks, blood samples were taken to measure cholesterol, triglyceride, HDL, LDL, ALT and AST. The animals were killed and the liver tissue was removed to examine the histopathological changes.Results: Feeding with a high-fat diet caused a significant increase in cholesterol, triglyceride and LDL-C in serum of rats compared to the control. Nano-silymarin and silymarin could significantly reduce serum triglyceride compared to negative group but the reduction of cholesterol, LDL-C, AST and ALT by nano-silymarin was not significant as compared to silymarin. The liver histology evaluation mainly showed that in the group receiving nano-silymarin, a significant decrease in the percentage of fat vacuoles and degree of steatosis was observed compared to the negative group. In the positive group, the percentage of fat vacuoles and the degree of steatosis showed a significant decrease compared to the negative group. Group receiving atorvastatin showed a greater protective effect than silymarin and nano-silymarin.Conclusion: The use of nano-silymarin similar to silymarin in rats treated with a high-fat diet led to a decrease in the percentage of fat vacuoles and the degree of hepatic steatosis mainly and can be used to prevent non-alcoholic fatty liver disease.

Abstract Purpose To analyze the role of and mechanism underlying obstructive sleep apnea (OSA)-derived exosomes in inducing non-alcoholic fatty liver (NAFLD). Methods The role of OSA-derived exosomes was analyzed in inducing hepatocyte fat accumulation in mice models both in vivo and in vitro. Results OSA-derived exosomes caused fat accumulation and macrophage activation in the liver tissue. These exosomes promoted fat accumulation; steatosis was more noticeable in the presence of macrophages. Macrophages could internalize OSA-derived exosomes, which promoted macrophage polarization to the M1 type. Moreover, it inhibited sirtuin-3 (SIRT3)/AMP-activated protein kinase (AMPK) and autophagy and promoted the activation of nucleotide-binding domain, leucine-rich–containing family, pyrin domain–containing-3 (NLRP3) inflammasomes. The use of 3-methyladenine (3-MA) to inhibit autophagy blocked NLRP3 inflammasome activation and inhibited the M1 polarization of macrophages. miR-421 targeting inhibited SIRT3 protein expression in the macrophages. miR-421 was significantly increased in OSA-derived exosomes. Additionally, miR-421 levels were increased in OSA + NAFLD mice- and patient-derived exosomes. In the liver tissues of OSA and OSA + NAFLD mice, miR-421 displayed similar co-localization with the macrophages. Intermittent hypoxia-induced hepatocytes deliver miR-421 to the macrophages via exosomes to inhibit SIRT3, thereby participating in macrophage M1 polarization. After OSA and NAFLD modeling in miR-421−/− mice, liver steatosis and M1 polarization were significantly reduced. Additionally, in the case of miR-421 knockout, the inhibitory effects of OSA-derived exosomes on SIRT3 and autophagy were significantly alleviated. Furthermore, their effects on liver steatosis and macrophage M1 polarization were significantly reduced. Conclusions OSA promotes the delivery of miR-421 from the hepatocytes to macrophages. Additionally, it promotes M1 polarization by regulating the SIRT3/AMPK-autophagy pathway, thereby causing NAFLD.

N-acetyl cysteine (NAC) is a versatile drug used in various conditions, but the limitations and toxicities are not clear. The acute toxicity and toxicological mechanisms of an intraperitoneal injection of NAC in normal mice were deciphered. The LD50 for male and female BALB/cByJNarl mice were 800 mg/kg and 933 mg/kg. The toxicological mechanisms of 800 mg/kg NAC (N800) were investigated. The serum biomarkers of hepatic and renal indices dramatically increased, followed by hepatic microvesicular steatosis, renal tubular injury and necrosis, and splenic red pulp atrophy and loss. Thus, N800 resulted in mouse mortality mainly due to acute liver, kidney, and spleen damages. The safe dose (275 mg/kg) of NAC (N275) increased hepatic antioxidant capacity by increasing glutathione levels and catalase activity. N275 elevated the hepatic gene expressions of lipid transporter, lipid synthesis, β-oxidation, and ketogenesis, suggesting a balance between lipid production and consumption, and finally, increased ATP production. In contrast, N800 increased hepatic oxidative stress by decreasing glutathione levels through suppressing Gclc, and reducing catalase activity. N800 decreased the hepatic gene expressions of lipid transporter, lipid synthesis, and interferred β-oxidation, leading to lipid accumulation and increasing Cyp2E1 expression, and finally, decreased ATP production. Therefore, NAC doses are limited for normal individuals, especially via intraperitoneal injection or similar means. [ABSTRACT FROM AUTHOR]

Background: Early identification and treatment of non-alcoholic fatty liver disease (NAFLD) could reduce overall mortality. Anthropometric measurements offer a simple and cost-effective method to potentially improve early detection of NAFLD and prevent its complications. This study aims to estimate the prevalence of NAFLD using the fatty liver index (FLI) and evaluate the effectiveness of certain anthropometric measurements in predicting NAFLD as diagnosed by FLI. Method: A cross-sectional analytical study was conducted with 1264 Saudi population without Type 2 diabetes mellitus (T2DM) non-alcoholic individuals at primary health care centers (PHCCs) in Jeddah city. Measurements included triglycerides, gamma-glutamyl transferase (GGT), glycated hemoglobin (HbA1c), and fasting plasma glucose (FPG). Measurements for neck circumference (NC), and calculations for weight-to-height ratio (WHtR) and weight-to-hip ratio (WHpR), along with FLI, were performed. NAFLD was identified in individuals with an FLI ⩾60. The receiver operating characteristic (ROC) curve analysis was utilized to assess the accuracy of WHtR, WHpR, and NC in detecting NAFLD, with Youden's index determining the optimal cutoff points for these 3 indices. Result: The prevalence of NAFLD was found to be 30.9%. Among the markers, WHtR emerged as the most significant in indicating NAFLD, achieving an area under the curve (AUC) of 0.916; whereas NC and WHpR exhibited identical AUC values of 0.783. WHtR demonstrated superior diagnostic efficacy for identifying elevated FLI, with gender-specific cutoff values established at >0.57 for females and >0.61 for males. In all 3 markers, females exhibited higher sensitivity, specificity, and negative predictive value (NPV) compared to males. Conclusion: WHtR could serve as a useful tool in the initial clinical screening for NAFLD among Saudi population without T2DM to identify those who may benefit from more comprehensive testing. Further local studies are warranted to confirm the levels of accuracy and the calculated cutoffs. [ABSTRACT FROM AUTHOR]

Aim: Non‐alcoholic fatty liver is the most common cause of chronic liver disease. GPR40 is a potential therapeutic target for energy metabolic disorders. GPR40 is a potential therapeutic target for energy metabolic disorders. SZZ15‐11 is a newly synthesized GPR40 agonist. In this study, we estimate the potency of SZZ15‐11 in fatty liver treatment. Methods: In vivo, diet‐induced obese (DIO) mice received SZZ15‐11 (50 mg/kg) and TAK875 (50 mg/kg) for 6 weeks. Blood glucose and lipid, hepatocyte lipid and liver morphology were analysed. In vitro, HepG2 cells and GPR40‐knockdown HepG2 cells induced with 0.3 mM oleic acid were treated with SZZ15‐11. Triglyceride and total cholesterol of cells were measured. At the same time, the AMPK pathway regulating triglycerides and cholesterol esters synthesis was investigated via western blot and quantitative polymerase chain reaction in both liver tissue and HepG2 cells. Results: SZZ15‐11 was found to not only attenuate hyperglycaemia and hyperlipidaemia but also ameliorate fatty liver disease in DIO mice. At the same time, SZZ15‐11 decreased triglyceride and total cholesterol content in HepG2 cells. Whether examined in the liver of DIO mice or in HepG2 cells, SZZ15‐11 upregulated AMPKα phosphorylation and then downregulated the expression of the cholesterogenic key enzyme 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase and inhibited acetyl‐CoA carboxylase activity. Furthermore, SZZ15‐11 promotes AMPK activity via [cAMP]i accumulation. Conclusion: This study confirmed that SZZ15‐11, a novel GPR40 agonist, improves hyperlipidaemia and fatty liver, partially via Gs signalling and the AMPK pathway in hepatocytes. [ABSTRACT FROM AUTHOR]

Objective To explore the mechanism of Canopy homolog 2 (CNPY2) and aerobic exercise through nuclear factor kappa-B (NF-kB) signal pathway in non-alcoholic fatty liver disease (NAFLD) induced by high fat diet. Methods Male CNPY2 knockout (CNPY2 KO) mice and wild (WT) mice aged (12±1) weeks were randomly divided into control group (CON), hyperlipidemic model group (MOD), and hyperlipidemic model exercise group (MOD+EX) after one week of adaptive feeding, CON group was fed with normal diet, and MOD group and MOD+EX group were fed with high fat diet until the end of 18 weeks. From the 10th week, the mice in the MOD+EX group received adaptive treadmill training for a week, followed by continuous exercise intervention until the end of the 18-week experiment The serum levels of TC, TG, LDL-C, HDL-C, ALT, and AST were detected by automatic biochemical analyzer, the pathological morphology of liver was analyzed by HE staining and oil red 0 staining, the protein expressions of CNPY2, IkB a, p-lKBot, NF-kB, and NF-kB in liver were detected by Western Blot, the levels of TNF-ot and IL6 in liver were detected by ELISA, and the expressions of NF-kB mRNA, TNF-a mRNA, and IL-6 mRNA in liver were detected by q RT-PCR. The data were analyzed by single factor analysis of variance and independent sample t -test. Results The expression of CNPY2 in MOD group was higher than that in CON group Q 二 一5.730, P=0.001) while the expression of CNPY2 in MOD+EX group was lower than that in MOD group(£=3.714, P=0.010). Compared with CON group, the serum levels of TC, TG, LDL-c, ALT, and AST in MOD group of WT mice and CNPY2 KO mice were higher (WT: £二一13.325, P < 0.001; £=-4.889, P < 0.001; i=-10.442, P < 0.001; £=-3.500： P=0.003; £=-15.122： P < 0.001; CNPY2 KO： =一6.910, P < 0.001; =-4.962, P < 0.001;匸一7.457, P < 0.001; =-4.584： P < 0.001;匸一7.336, P < 0.001). The levels of TNF-ot, IL-6, p~IKBa/lKBot, p-NF~kB/NF-kB, NF-kB mRNA, TNF-ct mRNA, and IL-6 mRNA in liver were increased significantly (WT: £=-25.179; P < 0,001; £=-21.043, P < 0.001; £=-9.177, P < 0,001; i=-12.207, P < 0.001;匸一5205, P=0.002; *-6.910, P < 0.001; z =-4.802, P二0.003; CNPY2 KO： e-18.87& P < 0.001; =-21.840, P < 0.001; h--14.033： P < 0.001; =--12.511, P < 0.001;匸一6.870： P < 0.001; =-9.546, P < 0,001;匸一8.303, P < 0.001), HDL-C level decreased (WT: 11.695, P < 0.001; CNPY2 KO: £=6.59& P < 0.001), and hepatocyte steatosis with large amount of lipid droplets was observed. Compared with MOD group, the above-mentioned indexes were effectively improved in WT mice and CNPY2 KO mice in MOD+EX group. Compared with WT mice, the above -mentioned indexes of CNPY2 KO mice were improved effectively. Conclusion CNPY2 regulates NF-kB signal pathway and participates in the formation and development of NAFLD. Both CNPY2 gene deletion and aerobic exercise can improve NAFLD, which may be related to the decrease of liver CNPY2 expression, inhibition of NF-kB signal pathway, down-regulation of liver inflammatory cytokines and reduction of liver inflammation. [ABSTRACT FROM AUTHOR]

Background and Aim: The study of lipid formation and degradation in response to dietary and exercise stimuli may provide a better perspective for preventing and treating nonalcoholic fatty liver disease. Therefore, this study aims to investigate the effects of diet, exercise, and hypoxia on the molecular mechanisms related to lipid metabolism. Materials and Methods: A total of twenty-four male Wistar rats aged approximately five weeks with an average weight of 165.9±9.94 grams were randomly divided into four groups including normal diet (ND), high-fat diet (HFD), high-fat diet+exercise in normoxia (HFD+NE), and high-fat diet+exercise in hypoxia (HFD+HE). The maximal aerobic velocity (MAV) was determined under normoxic conditions (at an altitude of approximately 50 m) and hypoxic-hypobaric conditions (at an altitude of approximately 3000 m). Following this, considering overload, exercise sessions were conducted three times a week for a duration of 12 weeks at intensities ranging from 68 to 80 percent of MAV. At the end, tissue samples were collected to measure changes in the expression of Srebf1, Chreb and Atgl genes. Gene expression was measured using Real-Time PCR method and data were analyzed using ANOVA and Tukey tests at a significance level of p<0.05. Results: The results showed that in all groups receiving a HFD, liver fat content and expression of Srebf1 and Chreb, genes were increased; whereas the increase in Srebf1 and Chreb was greater in the HFD+HE group than in the other groups. Moreover, Atgl gene expression was lower in the HFD group than in other groups. Conclusion: A HFD apparently increases liver fat content by increasing lipogenesis and decreasing lipolysis. Exercise is thought to regulate the increase in liver fat content in rats on HFD by increasing the expression of lipolysis genes. Training probably plays a lesser role than diet in altering lipogenic genes expression than nutrition. Hypoxic training had no additional effect on reducing liver fat content. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the role of and mechanism underlying obstructive sleep apnea (OSA)-derived exosomes in inducing non-alcoholic fatty liver (NAFLD). Methods: The role of OSA-derived exosomes was analyzed in inducing hepatocyte fat accumulation in mice models both in vivo and in vitro. Results: OSA-derived exosomes caused fat accumulation and macrophage activation in the liver tissue. These exosomes promoted fat accumulation; steatosis was more noticeable in the presence of macrophages. Macrophages could internalize OSA-derived exosomes, which promoted macrophage polarization to the M1 type. Moreover, it inhibited sirtuin-3 (SIRT3)/AMP-activated protein kinase (AMPK) and autophagy and promoted the activation of nucleotide-binding domain, leucine-rich–containing family, pyrin domain–containing-3 (NLRP3) inflammasomes. The use of 3-methyladenine (3-MA) to inhibit autophagy blocked NLRP3 inflammasome activation and inhibited the M1 polarization of macrophages. miR-421 targeting inhibited SIRT3 protein expression in the macrophages. miR-421 was significantly increased in OSA-derived exosomes. Additionally, miR-421 levels were increased in OSA + NAFLD mice- and patient-derived exosomes. In the liver tissues of OSA and OSA + NAFLD mice, miR-421 displayed similar co-localization with the macrophages. Intermittent hypoxia-induced hepatocytes deliver miR-421 to the macrophages via exosomes to inhibit SIRT3, thereby participating in macrophage M1 polarization. After OSA and NAFLD modeling in miR-421−/− mice, liver steatosis and M1 polarization were significantly reduced. Additionally, in the case of miR-421 knockout, the inhibitory effects of OSA-derived exosomes on SIRT3 and autophagy were significantly alleviated. Furthermore, their effects on liver steatosis and macrophage M1 polarization were significantly reduced. Conclusions: OSA promotes the delivery of miR-421 from the hepatocytes to macrophages. Additionally, it promotes M1 polarization by regulating the SIRT3/AMPK-autophagy pathway, thereby causing NAFLD. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) refers to the presence of hepatic steatosis (accumulation of fat in the liver to over 5% of its weight) in the absence of secondary causes of fat accumulation in the liver such as excessive alcohol use. NAFLD is divided into two types: non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH). Therefore, in this clinical guideline, we sought to determine general and important policies for this disease and modify its management approaches. We adapted this guideline for the management of NAFLD in Isfahan Province. This guideline was developed by clinical appraisal and review of the evidence, available clinical guidelines, and in consultation with members of the Isfahan Chamber of the Iranian Association of Gastroenterology and Hepatology. Biopsy is recommended as the most reliable method (gold standard) to diagnose steatohepatitis and fibrosis in patients with NAFLD. NAFLD fibrosis score (NFS) and fibrosis-4 (FIB-4) are recommended as the test with the highest predictive value for advanced fibrosis in patients with NAFLD compared to other serologic tests. Among the noninvasive methods used to assess liver fibrosis, transient elastography (TE) is preferable to other methods. [ABSTRACT FROM AUTHOR]

Objective: Considering the high prevalence of non-alcoholic fatty liver disease and its complications, this study aims to determine and compare the effect of nano-silymarin and silymarin on nonalcoholic fatty liver in rats. Materials and Methods: Rats were divided into 5 groups: Control, high-fat diet, high-fat diet and atorvastatin, high-fat diet and silymarin, and high-fat diet and nano-silymarin. After 12 weeks, blood samples were taken to measure cholesterol, triglyceride, HDL, LDL, ALT and AST. The animals were killed and the liver tissue was removed to examine the histopathological changes. Results: Feeding with a high-fat diet caused a significant increase in cholesterol, triglyceride and LDL-C in serum of rats compared to the control. Nano-silymarin and silymarin could significantly reduce serum triglyceride compared to negative group but the reduction of cholesterol, LDL-C, AST and ALT by nano-silymarin was not significant as compared to silymarin. The liver histology evaluation mainly showed that in the group receiving nanosilymarin, a significant decrease in the percentage of fat vacuoles and degree of steatosis was observed compared to the negative group. In the positive group, the percentage of fat vacuoles and the degree of steatosis showed a significant decrease compared to the negative group. Group receiving atorvastatin showed a greater protective effect than silymarin and nano-silymarin. Conclusion: The use of nano-silymarin similar to silymarin in rats treated with a high-fat diet led to a decrease in the percentage of fat vacuoles and the degree of hepatic steatosis mainly and can be used to prevent non-alcoholic fatty liver disease. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to assess the effect of sumac supplement in biochemical and anthropometric measurements in overweight or obese patients with non-alcoholic fatty liver disease. Materials and Methods: In this double-blind randomized controlled trial, 45 NAFLD patients were randomly divided into two groups. The intervention group received sumac capsules (3 g/day) with a balanced diet for 8 weeks, while the placebo group received placebo with a balanced diet. Anthropometric indices, lipid profile, fasting blood glucose, insulin, Homeostatic Model Assessment for Insulin Resistance, aspartate transaminase, alanine aminotransferase, high sensitivity C-reactive protein and malondialdehyde were measured at baseline and at the end of the study. Results: The results revealed a significant decrease in anthropometric indices (weight (p=0.001), body mass index (p=0.001), waist circumference (p=0.001), body fat mass (p=0.001), body fat percentage (p=0.001), visceral fat score (p=0.001), biochemical levels of total cholesterol (p=0.007), fasting blood sugar (p=0.006), insulin (p=0.004) and HOMA-IR (p=0.002)) after the intervention compared to the baseline. However, no significant difference was observed between the two groups concerning anthropometric and biochemical indices. Conclusion: In this study, no significant differences were observed between the two groups regarding anthropometric and biochemical indices. Thus, further studies with larger sample sizes are recommended to be conducted on the issue. [ABSTRACT FROM AUTHOR]

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This study investigates the effectiveness of Shenlin Baizhu powder in managing non-alcoholic fatty liver disease (NAFLD) during pregnancy and its mechanism through the PI3K/AKT/mTOR signaling pathway. Eight healthy male and 24 female Sprague-Dawley rats were used. After acclimatization, 6 female rats were fed normal chow, and 18 female rats were fed high-fat chow to induce NAFLD. After 8 weeks, female rats were mated with males to create a pregnant NAFLD model. The rats were divided into four groups: normal feeding, high-fat diet with saline, high-fat diet with 1.6 g/kg Shenlin Baizhu powder, and high-fat diet with 4.8 g/kg Shenlin Baizhu powder. Maternal body weight, serum and liver levels of aspartate aminotransferase (AST), alanine transaminase (ALT), triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), related inflammatory indexes interleukin-1 β (IL-1 β), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were measured. Liver tissue was examined using hematoxylin and oil red O staining, and protein expression related to the PI3K/AKT/mTOR pathway was assessed via Western blotting, immunohistochemistry and RT-PCR. Results showed significant weight gain and increases in ALT, AST, TG, TC, LDL-C, IL-1β, TNF-α, and IL-6, along with decreased HDL-C in NAFLD rats compared to controls. The high and low-dose Shenlin Baizhu powder groups exhibited improvements in body weight, liver histopathology, and reductions in serum TG, TC, LDL-C, ALT, AST, IL-1β, TNF-α, and IL-6, with increased HDL-C levels. Notably, the high-dose group showed greater efficacy in reducing hepatic fat accumulation, liver function markers, blood lipids, and inflammatory indexes, and decreased expression of hepatic PPARγ mRNA, SREBP1 mRNA, AKT mRNA, and related proteins. Shenlin Baizhu powder demonstrates potential in ameliorating high-fat diet-induced NAFLD in pregnant rats, likely through modulation of the PI3K/AKT/mTOR pathway, suggesting its therapeutic potential for gestational NAFLD.

Background: Non-alcoholic fatty liver disease is related to lipid accumulation and inflammation. Considering the role of lipin-1 and lipin-2 in fat homeostasis and inflammation, this study aimed to explore the effect of galbanic acid (Gal) and resveratrol (RSV) on alterations in the gene expression levels and protein abundance of lipin-1 and lipin-2 in HepG2 liver cells lipid-enriched with palmitate (Pal). Materials and Methods: HepG2 cells were subjected to different amounts of Gal and RSV for 24 hours in the presence of Pal to induce lipid accumulation. The RT-PCR method was employed to assess the expression of lipin-1 and lipin-2 genes, while protein levels were evaluated by western blot analysis. Lipid accumulation was determined qualitatively and semi-quantitatively using the oil-red staining technique. Results: Gal treatment increased lipin-1 and lipin-2 gene expression (P < 0.05). In contrast, the groups treated with RSV did not show a substantial variance in the expression levels of the two genes (P > 0.05). In the groups treated with Gal/RSV, the intensity of lipin-2 protein bands was higher compared to the Pal group (P > 0.01); however, the intensity of lipin-1 protein bands was not significantly different (P > 0.05). Conclusion: Gal, a coumarin compound, significantly increased the expression of lipin-1 and lipin-2 in HepG2 cells treated with Pal. Consequently, this research suggests gal as a novel strategy for regulating fat homeostasis in HepG2 cells.

Non-alcoholic fatty liver disease (NAFLD) is a prevalent liver disorder, affecting approximately 25 % of the population. Coffee-drinking obese smokers exhibit lower body weights and decreased NAFLD rates, but the reasons behind this remain unclear. Additionally, the effect of nicotine, the main component of tobacco, on the development of NAFLD is still controversial. Our study aimed to explore the possible reasons that drinking coffee could alleviate NAFLD and gain weight and identify the real role of nicotine in NAFLD of obese smokers. A NAFLD model in mice was induced by administering nicotine and a high-fat diet (HFD). We recorded changes in body weight and daily food intake, measured the weights of the liver and visceral fat, and observed liver and adipose tissue histopathology. Lipid levels, liver function, liver malondialdehyde (MDA), superoxide dismutase (SOD), serum inflammatory cytokine levels and the expression of hepatic genes involved in lipid metabolism were determined. Our results demonstrated that nicotine exacerbated the development of NAFLD and caffeine had a hepatoprotective effect on NAFLD. The administration of caffeine could ameliorate nicotine-plus-HFD-induced NAFLD by reducing lipid accumulation, regulating hepatic lipid metabolism, alleviating oxidative stress, attenuating inflammatory response and restoring hepatic functions. These results might explain why obese smokers with high coffee consumption exhibit the lower incidence rate of NAFLD and tend to be leaner. It is essential to emphasise that the detrimental impact of smoking on health is multifaceted. Smoking cessation remains the sole practical and effective strategy for averting the tobacco-related complications and reducing the risk of mortality. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the protective effect of Crataegus pinnatifida polysaccharide (CPP) on non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet (HFD) in mice. The findings demonstrated that CPP improved free fatty acid (FFA)-induced lipid accumulation in HepG2 cells and effectively reduced liver steatosis and epididymal fat weight in NAFLD mice, as well as decreased serum levels of TG, TC, AST, ALT, and LDL-C. Furthermore, CPP exhibited inhibitory effects on the expression of fatty acid synthesis genes FASN and ACC while activating the expression of fatty acid oxidation genes CPT1A and PPARa. Additionally, CPP reversed disturbances in intestinal microbiota composition caused by HFD consumption. CPP decreased the firmicutes/Bacteroidetes ratio, increased Akkermansia abundance, and elevated levels of total short-chain fatty acid (SCFA) content specifically butyric acid and acetic acid. Our results concluded that CPPmay intervene in the development of NAFLD by regulating of intes-tinal microbiota imbalance and SCFAs production. Our study highlights that CPP has a potential to modulate lipid-related pathways via alterations to gut microbiome composition thereby ex-erting inhibitory effects on obesity and NAFLD development. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we investigated the impact of a high-cholesterol, low-choline diet on non-alcoholic fatty liver disease (NAFLD) in laying hens, a condition known to decrease egg production. Our research focused on bile-acid metabolism as a potential avenue for addressing NAFLD. Using 7-week-old ISA female chickens, we induced NAFLD through a 6-week diet intervention, analyzed serum and cecal bile acids through LC/MS, and conducted 16S rRNA sequencing on cecal digesta DNA. The results revealed significant differences in bile-acid distribution between healthy and diet-induced NAFLD chickens. Notably, the diet led to alterations in both serum and cecal bile-acid profiles, affecting synthesis enzymes in the liver. Microbiota analysis demonstrated distinct differences in abundance and composition between the two groups. This study sheds light on the changes in bile acid and microflora associated with a chicken NAFLD model, contributing valuable insights into fatty liver disease metabolism and offering potential targets for intervention. Excessive liver fat causes non-alcoholic fatty liver disease (NAFLD) in laying hens, reducing egg production. Addressing NAFLD via bile-acid metabolism is gaining attention. We induced NAFLD in 7-week-old ISA female chickens with a high-cholesterol, low-choline diet (CLC) for 6 weeks. LC/MS was used to analyze serum and cecal bile acids, while cecal digesta DNA underwent 16S rRNA sequencing. The distribution of bile acid varied in healthy (CON) and CLC-fed chickens. CLC increased secondary bile acids (TLCA, TUDCA, THDCA, TDCA) in serum and primary bile acids (CDCA, TCDCA, isoDCA) in serum, as well as glycochenodeoxycholic acid (GCDCA) in cecal contents. CLC upregulated bile-acid synthesis enzymes (CYP7A1, CYP8B1) in the liver. Bile-acid receptor gene expression (HNF4A, FXR, LXR) was similar between groups. Microbiota abundance was richer in CON (alpha-diversity), with distinct separation (beta-diversity) between CON and CLC. The Firmicutes/Bacteroidetes ratio slightly decreased in CLC. Taxonomic analysis revealed higher Bacteroides, Alistipes, Megamonas in CLC but lower Barnesiella. CLC had more Mucispirillum, Eubacterium_coprostanoligenes_group, Shuttleworthia, and Olsenella, while CON had more Enterococcus, Ruminococcaceae_UCG_014, and Faecalibacterium. This study unveils bile-acid and microflora changes in a chicken NAFLD model, enhancing our understanding of fatty liver disease metabolism and aiding targeted interventions. [ABSTRACT FROM AUTHOR]

Objective: The prevalence of obesity and related comorbidities is increasing in children and adolescents. This study aimed to specify the prevalence of non-alcoholic fatty liver disease (NAFLD) in obese children and adolescents and to identify the predictive factors associated with NAFLD. Material and Methods: Obese children and adolescents aged 6 to 18 years were included in the study. The presence and degree of hepatosteatosis were evaluated using liver US. The groups with and without NAFLD were compared in terms of demographic, anthropometric, and biochemical parameters. Results: One hundred fifty-five obese children and adolescents with a median age of 13.8 (4.93) years (43 males, 131 pubertal) were included in the study. We found that 57.4% of obese cases had NAFLD. In the group with NAFLD, serum ALT level, AST level, HOMA-IR, and triglyceride level were significantly higher (p<0.001, p<0.001, p=0.015, p=0.021, respectively), and serum HDL-C level was significantly lower (p=0.001) compared to the group without NAFLD. In the binomial logistic regression analysis, age (ß=0.213, OR=1.23, p=0.040) and serum ALT level (ß=0.047, OR=1.04, p=0.011) were determining factors for hepatosteatosis. The diagnostic accuracy of elevated serum ALT level in detecting NAFLD was found to be 65.8% with a sensitivity of 77.3% and a specificity of 57.3% (+LR 1.81 and -LR 0.40). Conclusion: The prevalence of NAFLD determined with US in obese children and adolescents was 57.4%. Age and serum ALT level were found to be predictive factors for hepatosteatosis. Increased ALT alone shows insufficient performance in detecting NAFLD. [ABSTRACT FROM AUTHOR]

Lipophagy is a cellular pathway targeting the lysosomal degradation of lipid droplets, playing a role in promoting lipid turnover and renewal. Abnormal lipophagy processes can lead to the occurrence and development of non-alcoholic fatty liver disease (NAFLD), characterized by the deposition of lipid droplets (LDs) in the liver. The importance of exercise training in preventing and improving NAFLD has been well-established, but the exact mechanisms remain unclear. Recent research findings suggest that lipophagy may serve as a crucial hub for liver lipid turnover under exercise conditions. Exercise may alleviate hepatic lipid accumulation and mitigate inflammatory responses and fibrosis through lipophagy, thereby improving the onset and progression of NAFLD. [ABSTRACT FROM AUTHOR]

Background: The increasing prevalence of non-alcoholic fatty liver disease (NAFLD) in recent years has raised concerns about its significant risks for public health. According to previous studies, a diet with low phytochemicals and high inflammatory index is related to non-alcoholic fatty liver disease. In this study, we intend to investigate the relationship between inflammatory diet and phytochemical diet with NAFLD. Methods: In this case control study, 112 newly diagnosed patients with NAFLD referred to the Shahid Rahimi Hospital clinic in Khorramabad between January 1400 and April 1401 and 112 healthy individuals without NAFLD and any other chronic diseases as the control group, with the range 23-59 years old were selected. General information, demographics, physical activity level and food intake were collected using general information questionnaire, physical activity questionnaire and valid semi-quantitative food frequency questionnaire (FFQ). The energy received between the people of the two groups was adjusted. People's diet was divided into two anti-inflammatory and proinflammatory groups based on the DII index based on the score quartiles. Results: The results showed a significant relationship between DII score and NAFLD in the crude model (OR: 2.22, 95% CI: 1.04 -4.73), model I (adjusted for energy and age classification) (OR: 2.4, 95% CI:1.07-5.58), model II (adjusted for model I+physical activity, sex, education) (OR:2.77, 95% CI:1.14-6.77) and model III (model II+BMI) (OR: 2.16, 95% CI: 0.81-5.71) and DPI score and NAFLD the crude model (OR: 0.69, 95% CI: 0.32-1.47), model I (adjusted for energy and age classification) (OR: 0.56, 95% CI: 1.29-5.58), model II (adjusted for model I+physical activity, sex, education) (OR:0.58, 95% CI: 0.23-1.44) and model III (model II+BMI) (OR: 0.65, 95% CI: 0.24-1.75). Conclusion: The results obtained from this study showed an inverse relationship between following an anti-inflammatory diet and the risk of NAFLD. However, there was no correlation between receiving a diet with a high phytochemical index and NAFLD. [ABSTRACT FROM AUTHOR]

BackgroundNon-alcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disease. Portulaca oleracea exhibits anti-oxidant, anti-inflammatory, and hepatoprotective effects. This clinical trial aimed to investigate the potential benefits of Portulaca oleracea in improving NAFLD.MethodsThis double-blind, randomized clinical trial enrolled 70 patients with NAFLD assigned to either the intervention group (n = 35) or placebo group (n = 35) using stratified block randomization. The intervention group received 700 mg Portulaca oleracea supplement for eight weeks, while the control group received placebo capsules. In addition, all participants received a calorie-restricted diet. Liver steatosis and fibrosis were assessed using elastography along with liver function and metabolic tests, blood pressure measurements, body composition analysis and dietary records pre-and post-intervention.ResultsThe average age of the participants was 44.01 ± 8.6 years, of which 34 (48.6%) were women. The group receiving Portulaca oleracea showed significant weight changes, body mass index, fat mass index, and waist circumference compared to the placebo (p

The growing prevalence of NAFLD and its global health burden have provoked considerable research on possible diagnostic and therapeutic options for NAFLD. Although various pathophysiological mechanisms and genetic factors have been identified to be associated with NAFLD, its treatment remains challenging. In recent years, exosomes have attracted widespread attention for their role in metabolic dysfunctions and their efficacy as pathological biomarkers. Exosomes have also shown tremendous potential in treating a variety of disorders. With increasing evidence supporting the significant role of exosomes in NAFLD pathogenesis, their theragnostic potential has become a point of interest in NAFLD. Expectedly, exosome-based treatment strategies have shown promise in the prevention and amelioration of NAFLD in preclinical studies. However, there are still serious challenges in preparing, standardizing, and applying exosome-based therapies as a routine clinical option that should be overcome. Due to the great potential of this novel theragnostic agent in NAFLD, further investigations on their safety, clinical efficacy, and application standardization are highly recommended.

Abstract Introduction Non-alcoholic fatty liver disease (NAFLD) is a common liver disease characterized by an increase in fat in liver cells. The outbreak of NAFLD is estimated to be 32.4% worldwide, with higher rates in Asia and Iran. Nutritional factors such as excessive calorie intake, high fructose intake, copper deficiency, and increased iron intake play an important role in NAFLD. Since there is no specific treatment for NAFLD, intermittent fasting (IF) diet has been suggested as an alternative treatment for obesity and related complications. Previous studies showed the potential positive effects of IF on metabolic health and the reduction of oxidative stress in NAFLD. This randomized controlled trial (RCT) will be aimed to examine the effect of the IF diet in comparison with a low-calorie diet (LCD) on lipid profile, glycemic status, and liver fibrosis in patients with NAFLD. Methods and analysis This is a parallel randomized clinical trial conducted on 52 overweight and obese patients with NAFLD. Participants will be randomly assigned to receive either 16:8 IF (fasting from 8 P.M. to 12 P.M. the next day) or a low-calorie (55% carbohydrate- 30% fat, 15% protein) diet for 12 weeks. Anthropometric measurements, liver assessments, and metabolic evaluations will be assessed before and after the intervention. Primary outcomes include liver steatosis and fibrosis, while secondary outcomes include liver function enzymes, insulin resistance, lipid profile, and anthropometric measurements. Discussion Since obesity and insulin resistance are the most important risk factors of NAFLD, and there is no treatment for it, it seems that lifestyle changes such as low caloric diet like IF and exercise can improve lipid metabolism and liver enzymes. Trial registration Iranian registry of clinical trials (IRCT20170202032367N5).

Abstract Background and aims Excess energy intake can lead to metabolic dysfunction-associated steatotic liver disease (MASLD), but the relationship between dietary carbohydrate intake and liver fat content remains unclear. This study aimed to examine the associations between types and sources of dietary carbohydrates and liver fat content. Methods UK Biobank participants with no pre-existing diabetes, liver disease or cardiovascular disease reported dietary intake of types and sources of carbohydrates (total carbohydrates, free sugars, non-free sugars, starch from whole grains, starch from refined grains, and fibre) on at least two 24-h dietary assessments. In cross-sectional analyses, (n = 22,973), odds ratios (OR) of high liver fat content (defined as a score of ≥ 36 in the hepatic steatosis index) by quintiles of carbohydrate intakes were estimated using multivariable logistic regression models. In prospective analyses, a second sample (n = 9268) had liver proton density fat fraction (PDFF) measured by magnetic resonance imaging (2014–2020). Multivariable linear regression models estimated geometric means of PDFF (%) by quintiles of carbohydrate intakes. Models were adjusted for demographic and lifestyle confounders, including total energy intake. Results In the cross-sectional analyses, 6894 cases of high liver fat content were identified. Inverse associations between intakes of fibre (OR of highest vs. lowest quintile 0.46 [95% CI: 0.41–0.52]), non-free sugars (0.63 [0.57–0.70]) and starch from whole grains (0.52 [0.47–0.57]) with liver fat were observed. There were positive associations between starch from refined grains and liver fat (1.33 [1.21–1.46]), but no association with free sugars (p=0.61). In prospective analyses, inverse associations with PDFF (%) were observed for intakes of fibre (− 0.48 geometric mean difference between highest and lowest quintile of intake [− 0.60 to − 0.35]), non-free sugars (− 0.37 [− 0.49 to − 0.25]) and starch from whole grains (− 0.31 [− 0.42 to − 0.19]). Free sugars, but not starch from refined grains, were positively associated with PDFF (0.17 [0.05 to 0.28]). Conclusion This study suggests that different carbohydrate types and sources have varying associations with liver fat, which may be important for MASLD prevention. Non-free sugars, fibre, and starch from whole grains could be protective, while associations with free sugars and starch from refined grains are less clear.

Non-alcoholic fatty liver disease (NAFLD) refers to the presence of hepatic steatosis (accumulation of fat in the liver to over 5% of its weight) in the absence of secondary causes of fat accumulation in the liver such as excessive alcohol use. NAFLD is divided into two types: non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH). Therefore, in this clinical guideline, we sought to determine general and important policies for this disease and modify its managment approaches. We adapted this guideline for the management of NAFLD in Isfahan Province. This guideline was developed by clinical appraisal and review of the evidence, available clinical guidelines, and in consultation with members of the Isfahan Chamber of the Iranian Association of Gastroenterology and Hepatology. Biopsy is recommended as the most reliable method (gold standard) to diagnose steatohepatitis and fibrosis in patients with NAFLD. NAFLD fibrosis score (NFS) and fibrosis-4 (FIB-4) are recommended as the test with the highest predictive value for advanced fibrosis in patients with NAFLD compared to other serologic tests. Among the noninvasive methods used to assess liver fibrosis, transient elastography (TE) is preferable to other methods.

Abstract The response rate to obeticholic acid (OCA), a potential therapeutic agent for non-alcoholic fatty liver disease, is limited. This study demonstrated that upregulation of the alternative bile acid synthesis pathway increases the OCA treatment response rate. The hepatic transcriptome and bile acid metabolite profile analyses revealed that the alternative bile acid synthesis pathway (Cyp7b1 and muricholic acid) in the OCA-responder group were upregulated compared with those in the OCA-non-responder group. Intestinal microbiome analysis also revealed that the abundances of Bacteroidaceae, Parabacteroides, and Bacteroides, which were positively correlated with the alternative bile acid synthesis pathway, were higher in the OCA-responder group than in the non-responder group. Pre-study hepatic mRNA levels of Cyp8b1 (classic pathway) were downregulated in the OCA-responder group. The OCA response rate increased up to 80% in cases with a hepatic Cyp7b1/Cyp8b1 ratio ≥ 5.0. Therefore, the OCA therapeutic response can be evaluated based on the Cyp7b1/Cyp8b1 ratio or the alternative/classic bile acid synthesis pathway activity.

Background: In the context of Persian traditional medicine, there are several therapeutic strategies for managing diseases, ranging from lifestyle changes to herbal remedies. Objectives: Given the application of Persian traditional medicine in the management of chronic diseases, the burden of chronic illnesses, and the public’s recourse to traditional medicine specialists, this study aimed to assess the cost-effectiveness of traditional medicine dietary regimens for the treatment of non-alcoholic fatty liver disease from the perspective of the payer. Methods: In this study, we investigated the cost-effectiveness of providing nutrition counseling for lifestyle modification (changes in the aforementioned Setteh-e-Zarurieah) by a traditional medicine specialist compared to receiving counseling from a nutritionist for nonalcoholic fatty liver disease from the payer’s perspective. The outcomes measured were changes in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) enzymes, body mass index (BMI), and the grade of fatty liver. Cost and effectiveness data were entered into Excel software, and the ICER ratio was calculated. Results: The results indicated that the dietary regimen prescribed by Persian traditional medicine when compared to the nutritionist’s recommended diet, resulted in a lower decrease in AST and ALT enzymes but led to a greater decrease in BMI (mean change = 0.42) and a significant change in the grade of fatty liver (OR = 9.75). Since the costs of tests, ultrasounds, and visits were equal in both groups, the cost difference was zero. In the first scenario, where traditional medicine is considered an alternative therapy and liver enzymes are the primary focus, providing nutritional counseling services by Persian traditional medicine may not be cost effective. However, if we consider the grade of fatty liver and BMI as the primary variables, providing nutritional counseling services by Persian traditional medicine may be cost-effective. Conclusions: Based on the available evidence, the treatment of fatty liver using Persian traditional medicine can be considered an effective and cost-effective complementary (or alternative) intervention. Considering the long-term costs imposed by the health system and insurance organizations, it is predicted that adding visits to Persian traditional medicine specialists may reduce overall healthcare system costs.

BACKGROUND: In recent years, with the improvement of living standards, non-alcoholic fatty liver disease has a gradually increasing trend. miRNA-122 is one of the most abundant microRNAs in the liver, which plays an important role in maintaining the environmental stability and differentiation of the liver. Exercise training is a non-drug treatment for non-alcoholic fatty liver disease, which may improve liver lipid metabolism by regulating the expression of miRNA-122. OBJECTIVE: To review the effects of miRNA-122 on the pathological factors related to non-alcoholic fatty liver disease as well as the effects of exercise on the expression of miRNA-122 and the occurrence and development of nonalcoholic fatty liver disease. METHODS: The first author searched the databases of CNKI, WanFang, VIP, PubMed, Geenmedical, EBSCO, Medline, Web of Science, and Elsevier using “non-alcoholic fatty liver disease, microRNA, microRNA-122, lipid metabolism, inflammatory response, insulin resistance, exercise, physical exercise, exercise training” as the English and Chinese search terms for all relevant literature published before June 5, 2022. All included documents were screened, summarized, and analyzed. Finally, 68 documents were included for review. RESULTS AND CONCLUSION: Compared with the healthy control group, the expression of circulating miRNA-122 is increased in patients with non-alcoholic fatty liver disease. The level of miRNA-122 may show different expression levels at different stages of non-alcoholic fatty liver disease. miRNA-122 can regulate the expression of downstream-related proteins, influence lipid metabolism, inflammatory response, insulin resistance and other pathogenic factors in nonalcoholic fatty liver disease by targeting base complementary pairing sites on mRNA or directly acting as physiological ligands of some RNA receptors. Different exercise modes can improve non-alcoholic fatty liver disease. Therefore, patients with non-alcoholic fatty liver disease need to complete at least 120 minutes of moderate-intensity exercise every week to have a positive effect. For patients who can tolerate various exercises, priority should be given to the combination of aerobic and resistance exercises 4-5 times a week. The exercise intensity should be 50%-70% of the maximum heart rate and the exercise should last for > 3 months. For patients with poor tolerance, resistance exercise may be more feasible than aerobic exercise. In addition, patients with non-alcoholic fatty liver disease can also choose proper exercise modes according to their own disease conditions (such as liver enzymes and lipid levels). Exercise can be used as a feasible strategy to prevent non-alcoholic fatty liver disease, reduce liver steatosis, and alleviate liver inflammatory response and insulin resistance. Exercise training can regulate the expression of miRNA-122, but in patients with non-alcoholic fatty liver disease, the effect of exercise on miRNA-122 and its related signal pathways remains to be studied. [ABSTRACT FROM AUTHOR]

Background: In the context of Persian traditional medicine, there are several therapeutic strategies for managing diseases, ranging from lifestyle changes to herbal remedies. Objectives: Given the application of Persian traditional medicine in the management of chronic diseases, the burden of chronic illnesses, and the public's recourse to traditional medicine specialists, this study aimed to assess the cost-effectiveness of traditional medicine dietary regimens for the treatment of non-alcoholic fatty liver disease from the perspective of the payer. Methods: In this study, we investigated the cost-effectiveness of providing nutrition counseling for lifestyle modification (changes in the aforementioned Setteh-e-Zarurieah) by a traditional medicine specialist compared to receiving counseling from a nutritionist for non- alcoholic fatty liver disease from the payer's perspective. The outcomes measured were changes in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) enzymes, body mass index (BMI), and the grade of fatty liver. Cost and effectiveness data were entered into Excel software, and the ICER ratio was calculated. Results: The results indicated that the dietary regimen prescribed by Persian traditional medicine when compared to the nutritionist's recommended diet, resulted in a lower decrease in AST and ALT enzymes but led to a greater decrease in BMI (mean change = 0.42) and a significant change in the grade of fatty liver (OR = 9.75). Since the costs of tests, ultrasounds, and visits were equal in both groups, the cost difference was zero. In the first scenario, where traditional medicine is considered an alternative therapy and liver enzymes are the primary focus, providing nutritional counseling services by Persian traditional medicine may not be cost-effective. However, if we consider the grade of fatty liver and BMI as the primary variables, providing nutritional counseling services by Persian traditional medicine may be cost-effective. Conclusions: Based on the available evidence, the treatment of fatty liver using Persian traditional medicine can be considered an effective and cost-effective complementary (or alternative) intervention. Considering the long-term costs imposed by the health system and insurance organizations, it is predicted that adding visits to Persian traditional medicine specialists may reduce overall healthcare system costs. [ABSTRACT FROM AUTHOR]