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1.
World J Gastroenterol ; 30(20): 2633-2637, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38855152

ABSTRACT

This editorial builds on the article titled "Establishment and validation of an adherence prediction system for lifestyle interventions in non-alcoholic fatty liver disease" by Zeng et al. We carried out a critical examination of nonalcoholic fatty liver disease (NAFLD) pathogenesis and how lifestyle interventions could facilitate disease resolution, particularly highlighting that non-alcoholic steatohepatitis (NASH) is a severe form of NAFLD. Our discussion details that weight loss is a pivotal factor in disease outcomes: A 3%-5% reduction is enough for resolution in 50% of non-obese individuals, while a 7%-10% reduction achieves similar benefits in obese individuals, as demonstrated by magnetic resonance spectroscopy. Additionally, the editorial underscores that such lifestyle changes are instrumental not only in resolving NAFLD but also in reversing hepatic steatosis and inflammation. These insights, derived from the research, emphasize the critical role of personalized lifestyle modifications in halting the progression of NAFLD to NASH and even reversing fibrosis, thus offering a template for effective patient management.


Subject(s)
Disease Progression , Life Style , Non-alcoholic Fatty Liver Disease , Weight Loss , Non-alcoholic Fatty Liver Disease/therapy , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/etiology , Non-alcoholic Fatty Liver Disease/pathology , Humans , Obesity/diagnosis , Obesity/complications , Liver/pathology , Risk Reduction Behavior , Liver Cirrhosis/therapy , Liver Cirrhosis/pathology , Treatment Outcome
2.
World J Gastroenterol ; 30(20): 2629-2632, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38855158

ABSTRACT

This editorial delves into the research article by Zeng et al published in the latest issue of World Journal of Gastroenterology. The manuscript contributes significantly to addressing the global health issue of nonalcoholic fatty liver disease (NAFLD) by introducing and validating the Exercise and Diet Adherence Scale (EDAS). The article effectively conveys the importance of the study, highlighting the prevalence of NAFLD, the lack of approved drugs for its treatment, and the crucial role of lifestyle correction. The use of the Delphi method for scale deve-lopment and the subsequent evaluation of its reliability add scientific rigor to the methodology. The results demonstrate that the scale is correlated with key lifestyle indicators, which makes it a promising tool for assessing patient adherence to interventions. The identification of specific score thresholds for predicting adherence to daily calorie intake and exercise adds practical value to the scale. The differentiation among scores indicative of good, average, and poor adherence enhances its clinical applicability. In conclusion, the manuscript introduces EDAS, a valuable instrument that can contribute substantially to the field of NAFLD research and clinical practice.


Subject(s)
Exercise , Non-alcoholic Fatty Liver Disease , Patient Compliance , Humans , Non-alcoholic Fatty Liver Disease/therapy , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/epidemiology , Patient Compliance/statistics & numerical data , Reproducibility of Results , Life Style , Delphi Technique , Diet , Surveys and Questionnaires/statistics & numerical data
3.
Phytomedicine ; 130: 155756, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-38833791

ABSTRACT

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a persistent liver condition that affects both human health and animal productive efficiency on a global scale. A number of naturally occurring compounds activate nuclear factor erythroid 2-related factor 2 (Nrf2) as a transcription factor with important protective effects against many liver diseases, including NAFLD. Raffinose (Ra), an oligosaccharide extracted from several plants, exhibits diverse biological functions. However, the uncertainty lies in determining whether the activation of Nrf2 by Ra can provide a preventive effect on liver lipotoxicity. PURPOSE: The aim of this study was to shed light on the molecular pathways by which Ra possesses its protective benefits against NAFLD. METHODS: Experimental protocols were established using WT and Nrf2-null (Nrf2-/-) mice. Liver samples from each group were collected for Western blot, RT-qPCR, H & E, Sirius red and Oil red O staining. Additionally, serums were processed for ELISA. ALM12 cells were gathered for Western blot and immunofluorescence. Moreover, to elucidate the molecular mechanism of Ra, molecular docking was performed. RESULTS: Our results indicated that Ra remarkably alleviated liver lipotoxic in vivo and in vitro. Ra treatment effectively corrected hepatic steatosis, the release of AST, ALT, TG, and TC, as well as the depletion of HDL and LDL. Meanwhile, Ra efficiently prevented inflammation by inhibiting the TLR4-MyD88-NF-κB pathway and pyroptosis. Additionally, these findings implied that Ra reduced the production of fibrosis-related proteins, which enhanced collagen deposition. Molecular docking revealed that Ra possessed the ability to bind specific regions of Nrf2, resulting in the enhancement of Nrf2 activation and nuclear translocation. Ra treatment restored serum redox factors and antioxidant enzymes to normal levels; however, these alterations were clearly reversed in Nrf2-/- mice. CONCLUSION: This study reveals novel information on Ra's protective benefits against liver injury caused by abnormal lipid metabolism; these effects are mostly mediated by Nrf2 activation, suggesting a potential new medicine or treatment strategy for NAFLD.


Subject(s)
NF-E2-Related Factor 2 , Non-alcoholic Fatty Liver Disease , Pyroptosis , Animals , Non-alcoholic Fatty Liver Disease/drug therapy , NF-E2-Related Factor 2/metabolism , Pyroptosis/drug effects , Mice , Toll-Like Receptor 4/metabolism , Male , Lipid Metabolism/drug effects , Mice, Inbred C57BL , Inflammation/drug therapy , Liver/drug effects , Liver/metabolism , Molecular Docking Simulation , Antioxidants/pharmacology , Liver Cirrhosis/drug therapy , Liver Cirrhosis/metabolism , Mice, Knockout , Signal Transduction/drug effects , Myeloid Differentiation Factor 88/metabolism , NF-kappa B/metabolism
4.
BMC Cancer ; 24(1): 694, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38844890

ABSTRACT

BACKGROUND: Hepatocellular Carcinoma (HCC) can be classified as one of the most common malignancies worldwide. There is scarcity of the published data on the risk factors for HCC in the Gulf Cooperation Council countries specifically Kuwait. Therefore, this case-control study sought to examine the risk factors associated with HCC in Kuwait. METHODS: Fifty-three histopathologically confirmed HCC cases were recruited from the Kuwait Cancer Control Center Registry. One hundred ninety-six controls (1:4 ratio) were selected from medical and/ or surgical outpatient's clinics at all six public hospitals of Kuwait. A structured questionnaire was used to collect the data both from cases and controls through face-to-face interviews. A multivariable logistic regression model was fitted to the case-control data. Adjusted odds ratios (ORadj) and their 95% confidence intervals (CI) were computed using the parameters' estimates of the final model and used for interpretation of the model. RESULTS: The HCC cases compared with the controls were 41.6 times more likely to have had the history of non-alcoholic fatty liver disease (NAFLD) (ORadj = 41.6; 95% CI: 8.9-193.5; p < 0.001). The cases compared with the controls were more likely to have reported the history of heavy alcohol drinking (ORadj = 14.2; 95% CI: 1.2-173.4; p = 0.038). Furthermore, compared with the controls, the HCC cases tended to frequently consume milk and/or milk substitutes (≥ 3 glass/ week) (ORadj = 7.2; 95% CI: 1.2-43.4). Conversely however, there was a significant protective effect if the participants reportedly have had regularly used olive oil in their routine diet as a source of fat (ORadj = 0.17; 95% CI: 0.04-0.80) or regularly used non-steroid anti-inflammatory drugs (NSAIDs) (ORadj = 0.20; 95% CI: 0.05-0.71). CONCLUSIONS: This study showed that heavy alcohol consumption, NAFLD history, and excessive consumption of milk/ milk substitutes were associated with a significantly increased HCC risk. Conversely however, regular use of olive oil in the diet as a source of fat or regular use of NSAIDs had a significantly protective effect against HCC risk. Adapting healthy dietary habits and preventing/ treating NAFLD may minimize the HCC risk. Future research with a larger sample size may contemplate validating the results of this study and unraveling additional risk factors contributing to HCC risk. The resultant data may help design and implement evidence-based educational programs for the prevention of HCC in this and other similar settings.


Subject(s)
Carcinoma, Hepatocellular , Diet , Life Style , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/etiology , Liver Neoplasms/epidemiology , Female , Male , Case-Control Studies , Middle Aged , Risk Factors , Kuwait/epidemiology , Aged , Comorbidity , Adult , Alcohol Drinking/adverse effects , Alcohol Drinking/epidemiology , Non-alcoholic Fatty Liver Disease/epidemiology
5.
Cardiovasc Diabetol ; 23(1): 188, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38824550

ABSTRACT

BACKGROUNDS: Insulin resistance (IR) plays a vital role in the pathogenesis of the metabolic dysfunction-associated steatotic liver disease (MASLD). However, it remains unclear whether triglyceride-glucose (TyG) related parameters, which serve as useful biomarkers to assess IR, have prognostic effects on mortality outcomes of MASLD. METHODS: Participants in the National Health and Nutrition Examination Survey (NHANES) database from 1999 to 2018 years were included. TyG and its related parameters [TyG-waist circumference (TyG-WC) and TyG-waist to height ratio (TyG-WHtR)] were calculated. Kaplan-Meier curves, Cox regression analysis, and restricted cubic splines (RCS) were conducted to evaluate the association between TyG-related indices with the all-cause and cardiovascular mortality of adults with MASLD. The concordance index (C-index) was used to evaluate the prediction accuracy of TyG-related indices. RESULTS: A total of 8208 adults (4209 men and 3999 women, median age 49.00 years) with MASLD were included in this study. Multivariate-adjusted Cox regression analysis revealed that high quartile levels of TyG-related indices were significantly associated with the all-cause mortality of participants with MASLD [TyGadjusted hazard ratio (aHR) = 1.25, 95% confidence interval (CI) 1.05-1.50, P = 0.014; TyG-WCaHR for all-cause mortality = 1.28, 95% CI 1.07-1.52, P = 0.006; TyG-WHtRaHR for all-cause mortality = 1.50, 95% CI 1.25-1.80, P < 0.001; TyG-WCaHR for cardiovascular mortality = 1.81, 95% CI 1.28-2.55, P = 0.001; TyG-WHtRaHR for cardiovascular mortality = 2.22, 95% CI 1.55-3.17, P < 0.001]. The C-index of TyG-related indices for predicting all-cause mortality was 0.563 for the TyG index, 0.579 for the TyG-WC index, and 0.585 for the TyG-WHtR index, respectively. Regarding cardiovascular mortality, the C-index was 0.561 for the TyG index, 0.607 for the TyG-WC index, and 0.615 for the TyG-WHtR index, respectively. Nonlinear trends were observed between TyG and TyG-WC indices with all-cause mortality of MASLD (P < 0.001 and = 0.012, respectively). A non-linear relationship was observed between the TyG index and cardiovascular mortality of MASLD (P = 0.025). Subgroup analysis suggested that adults aged < 65 years old and those without comorbidities were more sensitive to the mortality prediction of TyG-related indices. CONCLUSION: Findings of this study highlight the predictive value of TyG-related indices, especially the TyG-WHtR index, in the mortality outcomes of adults with MASLD. TyG-related indices would be surrogate biomarkers for the clinical management of MASLD.


Subject(s)
Biomarkers , Blood Glucose , Cardiovascular Diseases , Cause of Death , Insulin Resistance , Nutrition Surveys , Triglycerides , Humans , Female , Male , Middle Aged , Triglycerides/blood , Prognosis , Risk Assessment , Biomarkers/blood , United States/epidemiology , Blood Glucose/metabolism , Cardiovascular Diseases/mortality , Cardiovascular Diseases/blood , Cardiovascular Diseases/diagnosis , Adult , Time Factors , Databases, Factual , Aged , Risk Factors , Non-alcoholic Fatty Liver Disease/mortality , Non-alcoholic Fatty Liver Disease/blood , Non-alcoholic Fatty Liver Disease/diagnosis , Cross-Sectional Studies , Predictive Value of Tests , Retrospective Studies
6.
Clin Transl Sci ; 17(6): e13760, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38847320

ABSTRACT

Metabolic dysfunction-associated steatohepatitis (MASH) is the severe form of non-alcoholic fatty liver disease which has a high potential to progress to cirrhosis and hepatocellular carcinoma, yet adequate effective therapies are lacking. Hypoadiponectinemia is causally involved in the pathogenesis of MASH. This study investigated the pharmacological effects of adiponectin replacement therapy with the adiponectin-derived peptide ALY688 (ALY688-SR) in a mouse model of MASH. Human induced pluripotent stem (iPS) cell-derived hepatocytes were used to test cytotoxicity and signaling of unmodified ALY688 in vitro. High-fat diet with low methionine and no added choline (CDAHF) was used to induce MASH and test the effects of ALY688-SR in vivo. Histological MASH activity score (NAS) and fibrosis score were determined to assess the effect of ALY688-SR. Transcriptional characterization of mice through RNA sequencing was performed to indicate potential molecular mechanisms involved. In cultured hepatocytes, ALY688 efficiently induced adiponectin-like signaling, including the AMP-activated protein kinase and p38 mitogen-activated protein kinase pathways, and did not elicit cytotoxicity. Administration of ALY688-SR in mice did not influence body weight but significantly ameliorated CDAHF-induced hepatic steatosis, inflammation, and fibrosis, therefore effectively preventing the development and progression of MASH. Mechanistically, ALY688-SR treatment markedly induced hepatic expression of genes involved in fatty acid oxidation, whereas it significantly suppressed the expression of pro-inflammatory and pro-fibrotic genes as demonstrated by transcriptomic analysis. ALY688-SR may represent an effective approach in MASH treatment. Its mode of action involves inhibition of hepatic steatosis, inflammation, and fibrosis, possibly via canonical adiponectin-mediated signaling.


Subject(s)
Adiponectin , Disease Models, Animal , Hepatocytes , Non-alcoholic Fatty Liver Disease , Animals , Adiponectin/metabolism , Adiponectin/pharmacology , Adiponectin/deficiency , Mice , Humans , Hepatocytes/metabolism , Hepatocytes/drug effects , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/prevention & control , Non-alcoholic Fatty Liver Disease/pathology , Non-alcoholic Fatty Liver Disease/etiology , Male , Mice, Inbred C57BL , Signal Transduction/drug effects , Diet, High-Fat/adverse effects , Metabolism, Inborn Errors/metabolism , Metabolism, Inborn Errors/drug therapy , Metabolism, Inborn Errors/pathology , Metabolic Diseases/drug therapy , Metabolic Diseases/metabolism , Metabolic Diseases/prevention & control , Metabolic Diseases/etiology , Liver/metabolism , Liver/drug effects , Liver/pathology , Fatty Liver/prevention & control , Fatty Liver/metabolism , Fatty Liver/drug therapy , Fatty Liver/pathology
7.
Medicine (Baltimore) ; 103(23): e38342, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38847670

ABSTRACT

In this study, we aimed to explore the clinical significance of serum CK18-M65 and CK18-M30 levels in patients with chronic hepatitis B (CHB) complicated by nonalcoholic steatohepatitis (NASH) and liver fibrosis. The observation and control groups comprised 133 patients with CHB complicated by NASH and 50 healthy patients from our hospital, respectively. Liver function indices, including alanine aminotransferase, glutamic aminotransferase, γ-glutamyltransferase, total bilirubin, total protein, and total cholesterol, were determined using an automatic biochemical analyzer. Hyaluronic acid, type III procollagen, type IV collagen, laminin, and CK18-M65 and M30 levels were detected using ELISA. Serum CK18-M65 and M30 levels in patients with CHB complicated by NASH were positively correlated with the liver fibrosis stage (P < .05). While serum CK18-M65 demonstrated a low diagnostic value for liver fibrosis in the S0-1 stage, it exhibited good diagnostic value for S2-3 stage liver fibrosis. Serum CK18-M30 displayed good diagnostic value for S0-1 and S2-3 hepatic fibrosis, particularly for S2-3 hepatic fibrosis. Elevated serum CK18-M65 and CK18-M30 levels in patients with CHB complicated with NASH suggest their potential utility in evaluating the progression of liver fibrosis in this population. In particular, CK18-M30 exhibits superior diagnostic efficiency.


Subject(s)
Biomarkers , Hepatitis B, Chronic , Keratin-18 , Liver Cirrhosis , Non-alcoholic Fatty Liver Disease , Humans , Non-alcoholic Fatty Liver Disease/blood , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/diagnosis , Hepatitis B, Chronic/blood , Hepatitis B, Chronic/complications , Male , Female , Keratin-18/blood , Liver Cirrhosis/blood , Liver Cirrhosis/diagnosis , Adult , Middle Aged , Biomarkers/blood , Peptide Fragments/blood , Liver Function Tests/methods , Case-Control Studies , Clinical Relevance
8.
Sci Rep ; 14(1): 12922, 2024 06 05.
Article in English | MEDLINE | ID: mdl-38839921

ABSTRACT

The incidence of non-alcoholic fatty liver disease (NAFLD) tends to be younger. And the role of theobromine in fatty liver disease remains unclear. The purpose of this study was to investigate the relationship between dietary theobromine intake and degree of hepatic steatosis in individuals aged 45 and below, using data from the 2017-2020 National Health and Nutrition Examination Survey (NHANES) and liver ultrasonography transient elastography. A total of 1796 participants aged below 45 years were included from NHANES 2017-2020 data after applying exclusion criteria. Multivariate regression and subgroup analyses were conducted to examine the associations between theobromine intake and controlled attenuation parameter (CAP), adjusting for potential confounders. Generalized additive models and two-piecewise linear regression were used to analyze nonlinear relationships. In the unadjusted Model 1 and preliminarily adjusted Model 2, there was no significant correlation between theobromine intake and CAP values. However, in Models 3 and 4, which accounted for confounding factors, a higher intake of theobromine was significantly associated with lower CAP values. Subgroup analyses in the fully adjusted Model 4 revealed a significant negative correlation among individuals aged 18-45, women, and white populations. Nonlinear analysis revealed a U-shaped relationship in black Americans, with the lowest CAP values at 44.5 mg/day theobromine. This study provides evidence that higher theobromine intake is correlated with lower degree of hepatic steatosis in young people, especially those aged 18-45 years, women, and whites. For black Americans, maintaining theobromine intake around 44.5 mg/day may help minimize liver steatosis. These findings may help personalize clinical nutritional guidance, prevent the degree of hepatic steatosis, and provide pharmacological approaches to reverse fatty liver disease in young people.


Subject(s)
Non-alcoholic Fatty Liver Disease , Nutrition Surveys , Theobromine , Humans , Theobromine/administration & dosage , Female , Male , Adult , Non-alcoholic Fatty Liver Disease/epidemiology , Adolescent , Young Adult , Middle Aged , Liver/diagnostic imaging , Liver/pathology , Elasticity Imaging Techniques , Fatty Liver/epidemiology , Fatty Liver/diagnostic imaging
9.
Front Endocrinol (Lausanne) ; 15: 1400448, 2024.
Article in English | MEDLINE | ID: mdl-38846493

ABSTRACT

Background and aims: According to previous studies, triglyceride-glucose (TyG) is related to chronic kidney disease (CKD), but no studies have explored the correlation between TyG and CKD among adults with metabolic dysfunction-associated fatty liver disease (MAFLD). We aimed to explore the associations of the TyG index with CKD among adults with MAFLD. Methods: In this retrospective observational cohort study, data from 11,860 participants who underwent a minimum of three health assessments between 2008 and 2015 were retrospectively collected. Participants were followed up until the final medical visit or health examination. CKD refers to an eGFR < 60 mL/min per 1·73 m2 or the occurrence of two or more incidents of proteinuria. Results: Within a median 10·02-year follow-up period, 2005 (16·9%) participants reported developing CKD. Multivariate Cox regression models indicated a noticeable correlation between the TyG index and CKD incidence (HR per unit increase, 1.19; 95% CI: 1.09-1.29) and between the TyG index and CKD incidence (HR per SD increase, 1.12; 95% CI: 1.06-1.18). The CKD incidence increased by 1.8 times in participants in the highest TyG index quartile relative to patients in the lowest quartile of the TyG index quartile (HR 1·18, 95% CI: 1.01-1.38, P = 0.007). According to subgroup analysis, an elevated TyG index is likely to become more harmful to participants younger than 60 years (P for interaction = 0.035). Conclusion: An elevated TyG index may increase CKD incidence among MAFLD adults, particularly among younger people. Early intervention may help reduce the incidence of CKD.


Subject(s)
Blood Glucose , Renal Insufficiency, Chronic , Triglycerides , Humans , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/epidemiology , Male , Female , Middle Aged , Triglycerides/blood , Retrospective Studies , Follow-Up Studies , Adult , Blood Glucose/analysis , Blood Glucose/metabolism , Incidence , Non-alcoholic Fatty Liver Disease/blood , Non-alcoholic Fatty Liver Disease/epidemiology , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/metabolism , Aged , Risk Factors
10.
Front Endocrinol (Lausanne) ; 15: 1329294, 2024.
Article in English | MEDLINE | ID: mdl-38828415

ABSTRACT

Aim: Short-term use of pemafibrate (PEM), a selective modulator of peroxisome proliferator-activated receptor alpha, has been reported to improve abnormal liver function in patients with nonalcoholic fatty liver disease with hypertriglyceridemia (HTG-NAFLD). This study aimed to clarify the effects and predictive factors of long-term 72-week PEM administration on body composition, and laboratory tests in HTG-NAFLD patients. Methods: Fifty-three HTG-NAFLD patients receiving a 72-week PEM regimen were retrospectively enrolled. Routine blood and body composition results were analyzed immediately before and at the end of the study period. Results: PEM treatment significantly improved liver enzyme levels such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, and gamma-glutamyl transferase, along with lipid profiles including triglyceride, total cholesterol, and low-density lipoprotein cholesterol. PEM did not have any detectable impact on body composition parameters. The factors of female, higher AST (≥ 46 U/L) and fat mass (≥ 31.9%), as well as lower soft lean mass (< 61.6%), skeletal muscle mass (< 36%), and skeletal muscle mass index (< 6.9 kg/m2) were significantly associated with the treatment response status of a > 30% decrease in ALT. All patients completed the treatment without any adverse effects. Conclusions: Long-term PEM treatment had a positive impact on liver enzymes and lipid profiles, but it did not result in significant changes in body composition among HTG-NAFLD patients. In predicting the response to PEM treatment, the evaluation of AST and body composition may be useful.


Subject(s)
Body Composition , Hypertriglyceridemia , Non-alcoholic Fatty Liver Disease , Humans , Female , Male , Middle Aged , Hypertriglyceridemia/drug therapy , Hypertriglyceridemia/complications , Hypertriglyceridemia/blood , Retrospective Studies , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/blood , Body Composition/drug effects , Benzoxazoles/therapeutic use , Benzoxazoles/administration & dosage , Adult , Butyrates/therapeutic use , Adipose Tissue/drug effects , Adipose Tissue/metabolism , Adipose Tissue/pathology , Aged , Hypolipidemic Agents/therapeutic use , Hypolipidemic Agents/administration & dosage
11.
Front Endocrinol (Lausanne) ; 15: 1343853, 2024.
Article in English | MEDLINE | ID: mdl-38828414

ABSTRACT

Introduction: Metabolic dysfunction-associated fatty liver disease (MAFLD) is closely associated with serum fibroblast growth factor (FGF) 21; however, previous studies have typically focused on the static fasting state, and the relationships between postprandial FGF21 levels, postprandial metabolic status, and MAFLD remain unclear. Therefore, we measured postprandial lipids, inflammatory factors, and FGF21 levels in MAFLD and further analyzed their relationship using an oral fat tolerance test (OFTT). Patients and methods: In total, 103 non-diabetic adult volunteers, including 46 patients with MAFLD, were included in this study. All participants underwent the OFTT. Venous blood samples were collected at 0, 2, 4, and 6 h. Circulating total cholesterol (TC), triglyceride (TG), free fatty acid (FFA), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), hypersensitive-C reactive protein(hs-CRP) and FGF21 were assessed. Results: Serum FGF21 significantly increased in the fasting state (P < 0.05) and showed a biphasic change of first decreasing and then increasing in MAFLD during the OFTT. The postprandial levels of TG, TC, LDL-C, FFA, IL-6, TNF-α and hs-CRP were significantly increased in MAFLD (P < 0.05). After adjusting for multiple factors, the FGF21 incremental area under the curve (iAUC) was linearly correlated with the FFA iAUC, TG iAUC, and IL-6 iAUC (P < 0.05) and was an independent factor for MAFLD (P < 0.05, OR=1.403). Conclusion: Dyslipidemia and excessive inflammation in MAFLD are associated to FGF21 levels in the postprandial period. An abnormal postprandial FGF21 response may be an important mechanism of MAFLD.


Subject(s)
Fibroblast Growth Factors , Inflammation , Postprandial Period , Humans , Fibroblast Growth Factors/blood , Male , Female , Middle Aged , Adult , Inflammation/blood , Inflammation/metabolism , Lipids/blood , Non-alcoholic Fatty Liver Disease/blood , Non-alcoholic Fatty Liver Disease/metabolism , Triglycerides/blood , Dietary Fats , Biomarkers/blood , Fatty Acids, Nonesterified/blood
12.
Sci Rep ; 14(1): 12829, 2024 06 04.
Article in English | MEDLINE | ID: mdl-38834647

ABSTRACT

The present cross-sectional study aimed to explore the relationship between systemic inflammatory indices (SIIs) and anthropometric measures, metabolic, and liver function biomarkers in patients with non-alcoholic fatty liver disease (NAFLD). This study was carried out on 238 NAFLD patients with overweight or obesity, aged 18-55 years. Anthropometric measurements were done and body mass index (BMI), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) were estimated. Metabolic factors including serum glucose, lipid profile, liver function biomarkers, and complete blood cell count were assessed after a 24-h fasting state. SIIs including the ratios of neutrophil to lymphocyte (NLR), monocytes to lymphocyte (MLR), platelet to lymphocyte (PLR), and monocytes to high-density lipoprotein cholesterol (MHR) were calculated. Results indicate that apart from PLR, all of the SIIs significantly changed by increasing steatosis severity (all p < 0.05). Moreover, changes in NLR showed a significant association with anthropometric indices including waist circumference (p = 0.032), BMI (p = 0.047), and WHtR (p = 0.002), as well as levels of fasting blood sugar (p = 0.045), triglycerides, (p = 0.025) and low-density lipoprotein cholesterol (p = 0.006). The findings also indicate the relations between lipid profile and all studied SIIs, notably MHR and MLR. All of the SIIs exhibited associations with some liver function indices as well. MHR was positively correlated with the metabolic risk factors of NAFLD while, oppositely, PLR was considered as a preventive marker of NAFLD.


Subject(s)
Body Mass Index , Non-alcoholic Fatty Liver Disease , Humans , Non-alcoholic Fatty Liver Disease/blood , Non-alcoholic Fatty Liver Disease/metabolism , Adult , Male , Female , Middle Aged , Cross-Sectional Studies , Adolescent , Young Adult , Inflammation/blood , Inflammation/metabolism , Biomarkers/blood , Liver/metabolism , Liver/pathology , Anthropometry , Obesity/complications , Obesity/metabolism , Obesity/blood , Liver Function Tests , Blood Glucose/metabolism , Waist-Hip Ratio
13.
BMC Endocr Disord ; 24(1): 79, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38834991

ABSTRACT

BACKGROUND: Research on Metabolic Associated Fatty Liver Disease (MAFLD) is still in its early stages, with few studies available to identify and predict effective indicators of this disease. On the other hand, early diagnosis and intervention are crucial to reduce the burden of MAFLD. Therefore, the aim of this research was to investigate the effectiveness of eleven anthropometric indices and their appropriate cut-off values as a non-invasive method to predict and diagnose MAFLD in the Iranian population. METHODS: In this cross-sectional study, we analyzed baseline data from the Hoveyzeh Cohort Study, a prospective population-based study conducted in Iran that enrolled a total of 7836 subjects aged 35 to 70 years from May 2016 through August 2018. RESULTS: The optimal cut-off values of anthropometric indices for predicting MAFLD risk were determined for waist circumference(WC) (102.25 cm for males and 101.45 cm for females), body mass index (BMI) (27.80 kg/m2 for males and 28.75 kg/m2 for females), waist-to-hip ratio (WHR) (0.96 for both males and females), waist-to-height ratio (WHtR) (0.56 for males and 0.63 for females), body adiposity index (BAI) (23.24 for males and 32.97 for females), visceral adiposity index (VAI) (1.64 for males and 1.88 for females), weight-adjusted waist index (WWI) (10.63 for males and 11.71 for females), conicity index (CI) (1.29 for males and 1.36 for females), body roundness index (BRI) (4.52 for males and 6.45 for females), relative fat mass (RFM) (28.18 for males and 44.91 for females) and abdominal volume index (AVI) (18.85 for males and for 21.37 females). VAI in males (sensitivity: 77%, specificity: 60%, Youden's Index: 0.37) and RFM in females (sensitivity: 76%, specificity: 59%, Youden's Index: 0.35) were found to have higher sensitivity and specificity compared to other anthropometric indices. Furthermore, anthropometric indices demonstrated statistically significant correlations with various hepatic and cardiometabolic indices. Among these, the strongest positive correlations were observed between WC, BMI, BAI, BRI, and AVI with the Hepatic Steatosis Index (HSI), TyG-BMI, and TyG-WC, as well as between VAI and the Atherogenic Index of Plasma (AIP), Lipid Accumulation Product (LAP), Cardiometabolic Index (CMI), and the Triglyceride and Glucose (TyG) Index. CONCLUSION: Anthropometric indices are effective in predicting MAFLD risk among Iranian adults, with WWI, VAI, and RFM identified as the strongest predictors. The proposed cutoff values could serve as a straightforward and non-invasive methods for the early diagnosis of MAFLD.


Subject(s)
Anthropometry , Humans , Male , Female , Middle Aged , Adult , Cross-Sectional Studies , Anthropometry/methods , Iran/epidemiology , Aged , Prospective Studies , Body Mass Index , Waist-Hip Ratio , Waist Circumference , Non-alcoholic Fatty Liver Disease/epidemiology , Non-alcoholic Fatty Liver Disease/diagnosis , Risk Factors , Prognosis , Adiposity , Metabolic Syndrome/diagnosis , Metabolic Syndrome/epidemiology , Follow-Up Studies
14.
Front Endocrinol (Lausanne) ; 15: 1371444, 2024.
Article in English | MEDLINE | ID: mdl-38836220

ABSTRACT

Objective: Individuals with hypopituitarism (HPs) have an increased risk of developing non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) due to growth hormone deficiency (GHD). We aimed to investigate the possible mechanisms underlying the relationship between GHD and NAFLD using proteomic and metabolomic insights. Methods: Serum metabolic alternations were assessed in male HPs using untargeted metabolomics. A rat model of HP was established through hypophysectomy, followed by recombinant human growth hormone (rhGH) intervention. The mechanisms underlying GHD-mediated NAFLD were elucidated through the application of label-free proteomics and phosphorylation proteomics. Results: Metabolomic analysis revealed that biomarkers of mitochondrial dysfunction and oxidative stress, such as alanine, lactate, and creatine, were significantly elevated in HPs compared to age-matched controls. In rats, hypophysectomy led to marked hepatic steatosis, lipid peroxidation, and reduced glutathione (GSH), which were subsequently modulated by rhGH replacement. Proteomic analysis identified cytochrome P450s, mitochondrial translation elongation, and PPARA activating genes as the major distinguishing pathways in hypophysectomized rats. The processes of fatty acid transport, synthesis, oxidation, and NADP metabolism were tightly described. An enhanced regulation of peroxisome ß-oxidation and ω-oxidation, together with a decreased NADPH regeneration, may exacerbate oxidative stress. Phosphoproteome data showed downregulation of JAK2-STAT5B and upregulation of mTOR signaling pathway. Conclusions: This study identified proteo-metabolomic signatures associated with the development of NAFLD in pituitary GHD. Evidence was found of oxidative stress imbalance resulting from abnormal fatty acid oxidation and NADPH regeneration, highlighting the role of GH deficiency in the development of NAFLD.


Subject(s)
Hypopituitarism , Metabolomics , Non-alcoholic Fatty Liver Disease , Oxidative Stress , Proteomics , Animals , Male , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/etiology , Rats , Hypopituitarism/metabolism , Hypopituitarism/etiology , Rats, Sprague-Dawley , Human Growth Hormone/deficiency , Human Growth Hormone/metabolism , Humans
15.
BMC Med ; 22(1): 221, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38825687

ABSTRACT

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) are implicated in the aetiology of non-communicable diseases. Our study aimed to evaluate associations between NAFLD and MetS with overall and cause-specific mortality. METHODS: We used dietary, lifestyle, anthropometric and metabolic biomarker data from a random subsample of 15,784 EPIC cohort participants. NAFLD was assessed using the fatty liver index (FLI) and MetS using the revised definition. Indices for metabolic dysfunction-associated fatty liver disease (MAFLD) were calculated. The individual associations of these indices with overall and cause-specific mortality were assessed using multivariable Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (95%CIs). As a subobjective, risk associations with adaptations of new classifications of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic and alcohol-related liver disease (MetALD) were also assessed. RESULTS: Among the 15,784 sub-cohort participants, a total of 1997 deaths occurred (835 due to cancer, 520 to CVD, 642 to other causes) over a median 15.6 (IQR, 12.3-17.1) years of follow-up. Compared to an FLI < 30, FLI ≥ 60 was associated with increased risks of overall mortality (HR = 1.44, 95%CI = 1.27-1.63), and deaths from cancer (HR = 1.32, 95%CI = 1.09-1.60), CVD (HR = 2.06, 95% CI = 1.61-2.63) or other causes (HR = 1.21, 95%CI = 0.97-1.51). Mortality risk associations were also elevated for individuals with MAFLD compared to those without. Individuals with MetS were at increased risk of all mortality endpoints, except cancer-specific mortality. MASLD and MetALD were associated with higher risk of overall mortality. CONCLUSIONS: Our findings based on a prospective cohort suggest that individuals with hepatic steatosis or metabolic dysfunction have a higher overall and cause-specific mortality risk.


Subject(s)
Metabolic Syndrome , Non-alcoholic Fatty Liver Disease , Humans , Male , Female , Middle Aged , Prospective Studies , Metabolic Syndrome/mortality , Non-alcoholic Fatty Liver Disease/mortality , Adult , Aged , Risk Factors , Cohort Studies , Fatty Liver/mortality
16.
J Appl Microbiol ; 135(6)2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38830802

ABSTRACT

AIMS: The incidence of nonalcoholic fatty liver disease (NAFLD) is increasing annually, leading to substantial medical and health burdens. Numerous studies have demonstrated the potential effectiveness of intestinal probiotics as a treatment strategy for NAFLD. Therefore, the objective of this study is to identify a probiotic for the treatment of NAFLD. METHODS AND RESULTS: In this study, blood and fecal samples were collected from 41 healthy volunteers and 44 patients diagnosed with NAFLD. Analysis of the 16S rDNA sequencing data and quantitative real-time PCR (RT-qPCR) revealed a significant reduction in the abundance of Coprococcus in NAFLD patients. Subsequent animal experiments demonstrated that Coprococcus was able to effectively reverse liver lipid accumulation, inflammation, and fibrosis induced by a high-fat diet (HFD) in mice. CONCLUSIONS: This study provides the first in vivo evidence that Coprococcus is a beneficial bacterium capable of preventing NAFLD and has the same probiotic effect in mice as Lactobacillus GG (LGG), a positive control. Therefore, Coprococcus has the potential to serve as a probiotic for the prevention and treatment of NAFLD in humans.


Subject(s)
Diet, High-Fat , Non-alcoholic Fatty Liver Disease , Probiotics , Animals , Non-alcoholic Fatty Liver Disease/prevention & control , Non-alcoholic Fatty Liver Disease/microbiology , Non-alcoholic Fatty Liver Disease/etiology , Diet, High-Fat/adverse effects , Probiotics/pharmacology , Probiotics/therapeutic use , Mice , Humans , Male , Mice, Inbred C57BL , Feces/microbiology , Feces/chemistry , Adult , Female , Liver/metabolism , Gastrointestinal Microbiome , Middle Aged , Disease Models, Animal
17.
Eur J Gastroenterol Hepatol ; 36(7): 961-969, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38829946

ABSTRACT

Fatty liver disease (FLD) affects approximately 25% of global adult population. Metabolic-associated fatty liver disease (MAFLD) is a term used to emphasize components of metabolic syndrome in FLD. MAFLD does not exclude coexistence of other liver disease, but impact of coexisting MAFLD is unclear. We investigated prevalence and characteristics of MAFLD in patients with biopsy-proven autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), or toxic liver disease. Liver histopathology and clinical data from Helsinki University Hospital district (1.7 million inhabitants) between 2009 and 2019 were collected from patients with AIH, PBC, PSC, or toxic liver disease at the time of diagnosis. MAFLD was diagnosed as macrovesicular steatosis ≥5% together with obesity, type-2 diabetes, or signs of metabolic dysregulation. Of 648 patients included, steatosis was observed in 15.6% (n = 101), of which 94.1% (n = 95) was due to MAFLD. Prevalence of coexisting MAFLD in the four liver diseases varied between 12.4 and 18.2% (P = 0.483). Fibrosis was more severe in MAFLD among patients with toxic liver disease (P = 0.01). Histopathological characteristics otherwise showed similar distribution among MAFLD and non-FLD controls. Alcohol consumption was higher in MAFLD group among patients with AIH or PBC (P < 0.05 for both). In AIH, smoking was more common in patients with coexisting MAFLD (P = 0.034). Prevalence of coexisting MAFLD in other primary liver diseases is lower than reported in general population. Histopathology of MAFLD patients did not clearly differ from non-FLD ones. Alcohol and smoking were associated with MAFLD in AIH.


Subject(s)
Cholangitis, Sclerosing , Hepatitis, Autoimmune , Liver Cirrhosis, Biliary , Humans , Male , Female , Middle Aged , Hepatitis, Autoimmune/complications , Hepatitis, Autoimmune/epidemiology , Prevalence , Liver Cirrhosis, Biliary/epidemiology , Liver Cirrhosis, Biliary/complications , Cholangitis, Sclerosing/complications , Cholangitis, Sclerosing/epidemiology , Adult , Finland/epidemiology , Aged , Chemical and Drug Induced Liver Injury/etiology , Chemical and Drug Induced Liver Injury/epidemiology , Fatty Liver/epidemiology , Fatty Liver/pathology , Fatty Liver/complications , Non-alcoholic Fatty Liver Disease/epidemiology , Non-alcoholic Fatty Liver Disease/complications , Obesity/complications , Obesity/epidemiology , Metabolic Syndrome/epidemiology , Metabolic Syndrome/complications , Biopsy , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Retrospective Studies , Risk Factors
18.
J Obes ; 2024: 7204607, 2024.
Article in English | MEDLINE | ID: mdl-38831961

ABSTRACT

Obesity is a complex chronic disease characterized by excess body fat (adipose) that is harmful to health and has been a major global health problem. It may be associated with several diseases, such as nonalcoholic fatty liver disease (NAFLD). Polyunsaturated fatty acids (PUFA) are lipid mediators that have anti-inflammatory characteristics and can be found in animals and plants, with capybara oil (CO) being a promising source. So, we intend to evaluate the hepatic pathophysiological alterations in C57Bl/6 mice with NAFLD, caused by obesity, and the possible beneficial effects of OC in the treatment of this disease. Eighteen 3-month-old male C57Bl/6 mice received a control or high-fat diet for 18 weeks. From the 15th to the 18th week, the animals received treatment-through orogastric gavage-with placebo or free capybara oil (5 g/kg). Parameters inherent to body mass, glucose tolerance, evaluation of liver enzymes, percentage of hepatic steatosis, oxidative stress, the process of cell death with the apoptotic biomarkers (Bax, Bcl2, and Cytochrome C), and the ultrastructure of hepatocytes were analyzed. Even though the treatment with CO was not able to disassemble the effects on the physiological parameters, it proved to be beneficial in reversing the morphological and ultrastructural damage present in the hepatocytes. Thus, demonstrating that CO has beneficial effects in reducing steatosis and the apoptotic pathway, it is a promising treatment for NAFLD.


Subject(s)
Apoptosis , Liver , Non-alcoholic Fatty Liver Disease , Oils , Rodentia , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease/etiology , Non-alcoholic Fatty Liver Disease/therapy , Male , Animals , Mice , Hepatocytes/drug effects , Hepatocytes/pathology , Hepatocytes/ultrastructure , Oils/pharmacology , Oils/therapeutic use , Obesity/complications , Apoptosis/drug effects , Liver/drug effects , Liver/pathology , Liver/ultrastructure , Oxidoreductases/metabolism , Enzyme Activation/drug effects , Oxidative Stress/drug effects
19.
Sci Rep ; 14(1): 13801, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38877074

ABSTRACT

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a predominant liver disease worldwide, lacking approved drugs for clinical intervention at present. The composite dietary antioxidant index (CDAI) is used to assess the anti-inflammatory properties of diets, with higher CDAI indicating greater exposure to antioxidants. Therefore, our study aimed to explore the relationship between CDAI and MASLD in order to identify potential therapeutic approaches. We collected data from 12,286 participants in the National Health and Nutrition Examination Survey (NHANES) database from 2017 to 2020 for analysis. The correlation between CDAI and MASLD status, controlled attenuation parameter (CAP), and liver stiffness measurement (LSM) was evaluated by adjusting for confounding variables using weighted binary logistic regression model, linear regression model, and restricted cubic spline (RCS) regression. The median CDAI in this study was - 0.3055 (interquartile range [IQR], - 2.299 to 2.290). The CDAI was higher in the population characterized by being young, female, higher income, absence of diabetes, and non-MASLD. After multivariable adjustment, the results of the weighted linear regression model suggested that higher CDAI may be associated with a decrease in CAP values; the results of the RCS regression model indicated significant non-linear relationships between MASLD status, CAP, LSM, and CDAI. The CDAI corresponding to the inflection points of the relationship curves between MASLD status, CAP, LSM, and CDAI were 0.349, 0.699, and 0.174, respectively. After further stratification by gender, we found that the relationship between MASLD status, CAP, and CDAI was significantly linear for females, whereas for males, it was non-linear, and the CDAI values corresponding to the inflection points in the curves for males were 1.325 and 0.985, respectively. We found that higher CDAI may be associated with decreased CAP values, particularly significant in females, suggesting that the intake of complex dietary antioxidants may ameliorate hepatic steatosis and reduce the occurrence of MASLD. Therefore, promoting dietary patterns rich in antioxidants may be an appropriate strategy to reduce the incidence of MASLD.


Subject(s)
Antioxidants , Nutrition Surveys , Humans , Male , Female , Antioxidants/metabolism , Cross-Sectional Studies , Adult , Middle Aged , Diet , Non-alcoholic Fatty Liver Disease/metabolism
20.
Nutr J ; 23(1): 64, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38872173

ABSTRACT

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a globally increasing health epidemic. Lifestyle intervention is recommended as the main therapy for NAFLD. However, the optimal approach is still unclear. This study aimed to evaluate the effects of a comprehensive approach of intensive lifestyle intervention (ILI) concerning enhanced control of calorie-restricted diet (CRD), exercise, and personalized nutrition counseling on liver steatosis and extrahepatic metabolic status in Chinese overweight and obese patients with NAFLD. METHODS: This study was a multicenter randomized controlled trial (RCT) conducted across seven hospitals in China. It involved 226 participants with a body mass index (BMI) above 25. These participants were randomly assigned to two groups: the ILI group, which followed a low carbohydrate, high protein CRD combined with exercise and intensive counseling from a dietitian, and a control group, which adhered to a balanced CRD along with exercise and standard counseling. The main measure of the study was the change in the fat attenuation parameter (FAP) from the start of the study to week 12, analyzed within the per-protocol set. Secondary measures included changes in BMI, liver stiffness measurement (LSM), and the improvement of various metabolic indexes. Additionally, predetermined subgroup analyses of the FAP were conducted based on variables like gender, age, BMI, ethnicity, hyperlipidemia, and hypertension. RESULTS: A total of 167 participants completed the whole study. Compared to the control group, ILI participants achieved a significant reduction in FAP (LS mean difference, 16.07 [95% CI: 8.90-23.25] dB/m) and BMI (LS mean difference, 1.46 [95% CI: 1.09-1.82] kg/m2) but not in LSM improvement (LS mean difference, 0.20 [95% CI: -0.19-0.59] kPa). The ILI also substantially improved other secondary outcomes (including ALT, AST, GGT, body fat mass, muscle mass and skeletal muscle mass, triglyceride, fasting blood glucose, fasting insulin, HbA1c, HOMA-IR, HOMA-ß, blood pressure, and homocysteine). Further subgroup analyses showed that ILI, rather than control intervention, led to more significant FAP reduction, especially in patients with concurrent hypertension (p < 0.001). CONCLUSION: In this RCT, a 12-week intensive lifestyle intervention program led to significant improvements in liver steatosis and other metabolic indicators in overweight and obese Chinese patients suffering from nonalcoholic fatty liver disease. Further research is required to confirm the long-term advantages and practicality of this approach. TRIAL REGISTRATION: This clinical trial was registered on ClinicalTrials.gov (registration number: NCT03972631) in June 2019.


Subject(s)
Caloric Restriction , Life Style , Non-alcoholic Fatty Liver Disease , Obesity , Overweight , Humans , Male , Female , Caloric Restriction/methods , China , Non-alcoholic Fatty Liver Disease/diet therapy , Non-alcoholic Fatty Liver Disease/therapy , Non-alcoholic Fatty Liver Disease/complications , Middle Aged , Obesity/diet therapy , Obesity/therapy , Obesity/complications , Overweight/therapy , Overweight/complications , Overweight/diet therapy , Adult , Liver/metabolism , Body Mass Index , Exercise/physiology , Counseling/methods
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