Nonalcoholic Fatty Liver Disease Research Articles

Does Breast Feeding Protect Mothers From Obesity?

Hepatosteatosis, which we frequently observe today with change in lifestyle, is often unnoticed, but preventable and reversible; if not prevented, it can lead to serious comorbidities. There is contradicting evidence in the literature; we believe that breastfeeding has a protective effect on hepatosteatosis. In this cross-sectional study we conducted, we aimed to examine the relationship between breastfeeding duration, metabolic parameters and fatty liver. We examined the data of 135 patients aged 20-40 years who have had at least one pregnancy and were admitted to our polyclinic. Forty-five healthcare staff who never breastfed were included in the control group. Measurements of height and weight were taken, and number of children and total breastfeeding time were questioned. Blood values were measured to calculate insulin resistance, non-alcoholic fatty liver disease (NAFLD) fibrosis score and Fibrosis-4 (FIB-4) score. Consequently, there was no significant correlation between total breastfeeding time and body mass index (BMI), NAFLD fibrosis score, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) value and hemoglobin A1C (HbA1C). When two groups were formed as patients breastfeeding for less than six months and patients breastfeeding for more than six months, a significant difference in BMI was observed between these two groups (p: 0.02). There was a significant relationship between BMI and NAFLD (p: 0.00) and HOMA-IR (p: 0.00). It was observed that there was a significant difference between BMI FIB-4 and NAFLD fibrosis scores of the control group and breastfed group. Lactation should be maintained for at least six months for maternal health together with the baby's health, and more comprehensive studies should be conducted for long-term data.

Prognostic Accuracy of Transient Elastography-Based Predictors in Diabetes and Obesity: A Multicenter International Cohort Study.

Liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) is recommended for risk stratification of patients with nonalcoholic fatty liver disease (NAFLD). More recently, AGILE3 + and AGILE4 have combined LSM with clinical parameters to identify patients with advanced fibrosis and cirrhosis, respectively. However, there are limited data on prognostic performance of these scores in key at-risk subgroups such as those with diabetes and obesity compared to LSM alone. This is a retrospective cohort study including 1903 adult patients with NAFLD from tertiary care centers in the United States and Singapore undergoing VCTE between 2015 and 2022. Primary predictors were FAST, LSM, AGILE3 + , and AGILE4 scores and the primary outcome was liver-related events (LRE). Patients were further stratified by diabetes and obesity status. Prognostic performance was measured using the time-dependent area under the receiver operating characteristic curve (tAUC) at 5years. In total, 25 LRE occurred and the overall incidence rate of LRE was 4.4 per 1000 person-years. tAUC for predicting LRE in the overall group was significantly higher with AGILE3 + (0.94 [95% CI: 0.90-0.98]) and AGILE4 (0.94 [95% CI: 0.90-0.98]) compared to LSM (0.87 [95% CI: 0.80-0.94]) (p = 0.001 and 0.009, respectively) and FAST (0.73 [95% CI: 0.59-0.86]) (p < 0.001 for both). Similarly, tAUC was significantly higher in those with T2D for AGILE3 + compared to LSM (0.92 vs 0.86, respectively) (p = 0.015) and FAST (0.92 vs 0.73, respectively) (p = 0.008). Among people with obesity, tAUC was significantly higher for AGILE3 + compared to LSM (0.95 vs 0.89, respectively) (p = 0.005) and FAST (0.95 vs 0.76, respectively) (p = 0.0035). Though AGILE4 had a higher tAUC in these subgroups compared to LSM, it did not reach statistical significance. AGILE3 + significantly outperforms LSM and FAST for predicting LRE in patients with NAFLD including in those with diabetes or obesity.

Exercise training alleviates cholesterol and lipid accumulation in mice with non-alcoholic steatohepatitis: Reduction of KMT2D-mediated histone methylation of IDI1

Exercise training is a cornerstone treatment for non-alcoholic fatty liver disease (NAFLD). This study aims to investigate the effects of exercises on lipid accumulation in non-alcoholic steatohepatitis (NASH) and to explore the molecular mechanism. Established NASH mice were remained sedentary or subjected to moderate-intensity continuous training or high-intensity interval training (HIIT). The two training regimens, especially the latter one, reduced liver weight, steatosis, inflammation, lipid accumulation, collagen deposition, and cholesterol content in the mouse liver. Similarly, the HIIT regimen improved clinical presentation of NAFLD patients. RNA sequencing analysis revealed lysine methyltransferase 2D (Kmt2d) and isopentenyl-diphosphate delta isomerase 1 (Idi1) as two important genes downregulated in mice underwent HIIT. By using mouse hepatocytes AML12, we found that KMT2D promoted Idi1 expression by catalyzing H3K4me1 modification near its promoter. Upregulation of either KMT2D or IDI1 blocked the ameliorating effects of HIIT on mice. Meanwhile, in AML12 cells modeled by palmitic acid and oleic acid treatment, KMT2D and IDI1 were found to be correlated with lipid accumulation, cholesterol content, inflammation, and cell death and senescence. In conclusion, this study demonstrates that the ameliorating effects of exercise training on NASH might involve the downregulation of the KMT2D/IDI1 axis.

Semaglutide treatment for children with obesity: an observational study

ObjectiveTo assess efficacy and tolerability of semaglutide as a weight loss treatment for children living with comorbid obesity.DesignRetrospective observational study of the first 50 children from a weight management service...

Identifying metabolic dysfunction-associated steatotic liver disease in patients with type 2 diabetes mellitus using clinic-based prediction tools.

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is a global cause of chronic liver disease. The prevalence of MASLD is high in patients with type 2 diabetes mellitus (T2DM). Various non-invasive tools such as the fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS), liver ultrasound, and FibroScan can aid in the detection of liver fibrosis in MASLD, while the Hamaguchi ultrasound-based liver grading system has demonstrated high sensitivity and specificity comparable to liver biopsy. We assessed the frequency of MASLD in patients with T2DM using the liver ultrasound Hamaguchi score and the accuracy of NFS and Fib-4 in identifying MASLD. We retrospectively collected data and reviewed the charts of all patients with T2DM who underwent liver ultrasound and laboratory tests during the past 5 years. A total of 6,214 medical records were screened, and only 153 patients (68.6% women; mean age, 59 ± 12.2 years) fulfilled the selection criteria. MASLD was diagnosed using the Hamaguchi grading criteria in 45.1% of patients. A high/intermediate NFS had a higher sensitivity (79.7%) for diagnosing MASLD with a specificity of 10.7%, while a high/intermediate Fib-4 score showed only 30.4% sensitivity but a higher specificity of 54.8%. Our study indicates that MASLD is frequent in patients with T2DM, and clinical prediction tools such as NFS and Fib-4 can be applied in clinic/primary care settings with variable results.

Metabolic Dysfunction-Associated Steatotic Liver Disease in Patients with Inflammatory Bowel Diseases: A Pilot Study.

Inflammatory bowel disease (IBD) is characterized by persistent inflammation and is often associated with metabolic dysfunction-associated steatotic liver disease (MASLD). IBD patients are at risk of developing MASLD due to shared risk factors such as gut dysbiosis and systemic inflammation. The new MASLD nomenclature emphasizes the link between liver steatosis and cardiometabolic comorbidities. However, the prevalence of MASLD in IBD patients remains poorly explored. The main aim of this cross-sectional study is to assess the prevalence of ultrasound (US) and the clinical features of MASLD in patients with IBDs. We conducted a retrospective study enrolling 272 Italian IBD patients attending Renato Dulbecco Teaching Hospital in a period between 1 January 2021 and 31 December 2023. MASLD was diagnosed based on the presence of liver steatosis with cardiometabolic risk factors, using established guidelines. Demographic, clinical, and laboratory data were collected and analyzed. Statistical significance was determined at a p-value < 0.05. Of the 272 IBD patients, 6% had non-alcoholic fatty liver disease (NAFLD), while 18% had MASLD. Patients with IBD-MASLD were significantly older, had higher body mass index, waist circumference, and triglyceride levels, and were more likely to have type 2 diabetes mellitus and hypertension compared to those with IBD-NAFLD. IBD-MASLD patients also showed higher disease activity scores and required more frequent surgical interventions. Bivariate logistic regression revealed triglyceride levels as a significant predictor of MASLD in IBD patients. MASLD is more prevalent in IBD patients, highlighting the importance of early detection of liver steatosis in this at-risk population. The association between MASLD and cardiometabolic risk factors underscores the need for a multidisciplinary approach to manage these patients effectively. Further studies in larger cohorts are necessary to confirm these findings and explore the pathophysiological mechanisms involved.

Liver-specific actions of GH and IGF1 that protect against MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD; also known as nonalcoholic fatty liver disease) is a chronic condition associated with metabolic syndrome, a group of conditions that includes obesity, insulin resistance, hyperlipidaemia and cardiovascular disease. Primary growth hormone (GH) deficiency is associated with MASLD, and the decline in circulating levels of GH with weight gain might contribute to the development of MASLD. Raising endogenous GH secretion or administering GH replacement therapy in the context of MASLD enhances insulin-like growth factor 1 (IGF1) production and reduces steatosis and the severity of liver injury. GH and IGF1 indirectly control MASLD progression by regulating systemic metabolic function. Evidence supports the proposal that GH and IGF1 also have a direct role in regulating liver metabolism and health. This Review focuses on how GH acts on the hepatocyte in a sex-dependent manner to limit lipid accumulation, reduce stress, and promote survival and regeneration. In addition, we discuss how GH and IGF1 might regulate non-parenchymal cells of the liver to control inflammation and fibrosis, which have a major effect on hepatocyte survival and regeneration. Development of a better understanding of how GH and IGF1 coordinate the functions of specific, individual liver cell types might provide insight into the aetiology of MASLD initiation and progression and suggest novel approaches for the treatment of MASLD.

Polysaccharides from Tremella Fuciformis Enhance Glucose and Lipid Metabolism in HepG2 Cells Through Activating the AMPK Signaling Pathway.

Polysaccharides have gained substantial attention for their diverse biological activities. The present study was conucted to elucidate the effects and molecular mechanisms of Tremella fuciformis-derived polysaccharides (PTP-3a) on glucose and lipid metabolism in palmitic acid (PA) - treated HepG2 cells. Multiple parameters were assessed following PTP-3a treatment, including lipid accumulation, glycogen content, glucose consumption, and enzyme activities, including pyruvate kinase (PK) and hexokinase (HK). Additionally, the expression levels of genes associated with glucose and lipid metabolism was evaluated using western blot analysis. PTP-3a effectively inhibited lipid accumulation, promoted the glucose consumption, increased the amount of cellular glycogen, and enhanced PK and HK activities in PA-treated cells. Furthermore, PTP-3a induced a significant increase in the p-AMPK/AMPK ratio and the expression level of PPARa, while decreasing the expression levels of SREBP, FAS, ACC, and SOCS3. In conclusion, these findings suggested that PTP-3a exerted beneficial effects on glucose and lipid metabolism by activating the AMPK signaling pathway, resulting in the inhibition of lipogenesis, promotion of fatty acid oxidation, and enhancement of cellular glycogen synthesis and glycolysis. These findings hold clinical relevance and provide a foundation for potential treatments for non-alcoholic fatty liver disease (NAFLD) and and related metabolic disorders.

Progression from Non-alcoholic Steatohepatitis to Advanced Liver Diseases and Mortality Among Medicare Patients.

Non-alcoholic steatohepatitis (NASH) may progress to more advanced liver disease. This study aimed to characterize NASH progression and mortality in the Medicare population. Patients with NASH in 100% Medicare fee-for-service claims accrued from2015-2021 who were≥66years old at index diagnosis, continuously enrolled for≥12months prior to and≥6months following index (unless death), and had no evidence of other causes of liver disease were included. Diagnosis codes defined severity states: non-cirrhotic NASH, compensated cirrhosis (CC), decompensated cirrhosis (DCC), hepatocellular carcinoma (HCC), and liver transplant (LT). Survival analyses of disease progression and mortality were conducted for each state and by year of progression (Y1-5). Cox proportional hazards models assessed risk factors of worsening disease. Mean age and follow-up were 72.2 and 2.8years in 14,806 unique patients (n=12,990 NASH; 1899 CC; 997 DCC; 209 HCC; 140 LT). Progression rates were highest for patients with CC (11-37% for Y1-5), followed by DCC (3-18%), NASH (3-12%), and HCC (2-4%). Mortality rates were highest for patients with HCC (41-85% for Y1-5), followed by DCC (41-76%), LT (7-33%), CC (6-26%), and NASH (2-12%). Patients with any disease progression had a 5-year mortality rate more than double that of patients without progression (41% vs. 16%). Delayed progression from NASH was associated with lower mortality risk; the 5-year mortality rate was 26% lower for patients with progression in Y2 vs. Y1 (32% vs. 43%) and further decreased for progression in Y3-Y5. Risk factors included age, nursing home use, congestive heart failure, coagulopathy, fluid/electrolyte disorders, and unexplained weight loss. Medicare patients≥66years with NASH experience high risk of disease progression associated with increased mortality rates. Slower disease progression is associated with lower mortality rates, suggesting that therapies that can delay or prevent NASH progression may reduce morbidity and mortality.

The impact of vildagliptin as an add-on therapy on matrix metalloproteinase-14 levels, liver stiffness and subclinical atherosclerosis in adolescents with type 1 diabetes and non-alcoholic steatohepatitis: A randomized controlled trial.

Many patients with type 1 diabetes mellitus (T1DM) met the histological criteria for non-alcoholic steatohepatitis (NASH), which leads to cardiovascular disease morbidity and mortality. Matrix metalloproteinase-14 (MMP-14) is involved in cardiovascular disease and atherosclerosis. To assess the impact of oral dipeptidyl peptidase-4 inhibitor, vildagliptin, as adjunctive therapy on NASH in adolescents with T1DM and its effect on glycaemic control, MMP-14 levels and carotid intima media thickness (CIMT). Sixty adolescents with T1DM and NASH were randomly assigned to receive oral vildagliptin (50 mg once daily) for 6 months or not. Glycated haemoglobin, lipid profile, hepatic steatosis index, triglyceride glucose (TyG) index and MMP-14 levels were assessed. Transient elastography with controlled attenuation parameter (CAP) was performed together with measuring CIMT. By transient elastography, 12 (20%) patients with T1DM with NASH had elevated liver stiffness ≥7 kPa (F2 stage or higher). Baseline MMP-14 was positively correlated to insulin dose (p = 0.016), triglycerides and TyG index, CIMT, liver stiffness and CAP levels among the studied patients (p < 0.001 for all). After 6 months, patients with T1DM on vildagliptin therapy had significantly lower glycated haemoglobin, lipid profile, hepatic steatosis index and TyG index, as well as MMP-14 (p < 0.001). CIMT, liver stiffness and CAP were significantly decreased post-therapy compared with baseline levels and compared with the control group (p < 0.001). Vildagliptin was safe and well-tolerated. Administration of vildagliptin for adolescents with T1DM and NASH improved glycaemic control, dyslipidaemia and MMP-14 levels and decreased liver stiffness and CIMT; hence, reducing subclinical atherosclerosis and disease progression.

Non-Invasive Serum Markers of Non-Alcoholic Fatty Liver Disease Fibrosis: Potential Tools for Detecting Patients with Cardiovascular Disease.

Non-alcoholic fatty liver disease (NAFLD), one of the most common chronic liver diseases with a prevalence of 23%-25% globally, is an independent risk factor for cardiovascular diseases (CVDs). Growing evidence indicates that the development of NAFLD, ranging from non-alcoholic fatty liver (NAFL), non-alcoholic steatohepatitis (NASH), advanced fibrosis to cirrhosis, and even hepatocellular carcinoma, is at substantial risk for CVDs, which clinically contribute to increased cardiovascular morbidity and mortality. Non-invasive serum markers assessing liver fibrosis, such as fibrosis-4 (FIB-4) score, aspartate transaminase-to-platelet ratio index (APRI), and NAFLD fibrosis score (NFS), are expected to be useful tools for clinical management of patients with CVDs. This review aims to provide an overview of the evidence for the relationship between the progression of NAFLD and CVDs and the clinical application of non-invasive markers of liver fibrosis in managing patients with CVDs.

Extra Virgin Olive Oil Reduces the Risk of Non-Alcoholic Fatty Liver Disease in Females but Not in Males: Results from the NUTRIHEP Cohort

Background: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide. One way to resolve this reversible condition is by making dietary changes. Extra virgin olive oil (EVOO) is often associated with an improvement in this disease. The aim of this study was to explore the protective role of EVOO on NAFLD conditions, stratified by gender. Methods: The study cohort included 1426 participants assessed in the second recall of the NUTRIHEP cohort (2014–2018), subdivided by gender and dividing the EVOO intake into quartiles of daily gram intake. Results: The results indicated a protective role of the last quartile of EVOO only for female subjects, OR = 0.43, p = 0.02, 0.21 to 0.85 at 95% C.I., whereas in the male sub-cohort, the effect was not statistically significant. Conclusions: The protective role of EVOO is different between genders. This difference has not been explored in the literature, so we conclude that this is one of the few papers in the literature to evaluate a gender difference in the intestinal absorption of humans based on an epidemiological study.

Significance of Immune and Non-Immune Cell Stroma as a Microenvironment of Hepatocellular Carcinoma—From Inflammation to Hepatocellular Carcinoma Progression

Hepatocellular carcinoma (HCC) is the most common liver cancer as well as the most prevalent cause of death in the adult patient population with cirrhosis. The occurrence of HCC is primarily caused by chronic liver inflammation that might occur because of a viral infection, non-alcoholic fatty liver disease (NAFLD), or various lifestyle-associated factors. The objective of this review was to summarize the current knowledge regarding the microenvironment of HCC, indicating how immune- and non-immune-cell stroma might affect the onset and progression of HCC. Therefore, in the following narrative review, we described the role of tumor-infiltrating neutrophils, bone-marrow-derived cells, tumor-associated mast cells, cancer-associated fibroblasts, tumor-associated macrophages, liver-sinusoidal endothelial cells, lymphocytes, and certain cytokines in liver inflammation and the further progression to HCC. A better understanding of the HCC microenvironment might be crucial to introducing novel treatment strategies or combined therapies that could lead to more effective clinical outcomes.

New Application of an Old Drug: Anti-Diabetic Properties of Phloroglucinol.

Phloroglucinol (PHG), an analgesic and spasmolytic drug, shows promise in preventing high-fat-diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) and insulin resistance. In Wistar rats, 10 weeks of PHG treatment did not prevent HFD-induced weight gain but significantly mitigated fasting hyperglycemia, impaired insulin responses, and liver steatosis. This protective effect was not linked to hepatic lipogenesis or AMP-activated protein kinase (AMPK) activation. Instead, PHG improved mitochondrial function by reducing oxidative stress, enhancing ATP production, and increasing anti-oxidant enzyme activity. PHG also relaxed gastric smooth muscles via potassium channel activation and nitric oxide (NO) signaling, potentially delaying gastric emptying. A pilot intervention in pre-diabetic men confirmed PHG's efficacy in improving postprandial glycemic control and altering lipid metabolism. These findings suggest PHG as a potential therapeutic for NAFLD and insulin resistance, acting through mechanisms involving mitochondrial protection, anti-oxidant activity, and gastric motility modulation. Further clinical evaluation is warranted to explore PHG's full therapeutic potential.

Tea intake and non-alcoholic fatty liver disease risk: A two-sample Mendelian randomization study

BackgroundNon-alcoholic fatty liver disease (NAFLD) is a major global health problem due to its great disease and economic burdens. Tea is a popular beverage consumed by billions of people.globally owing to its health benefits. However, the evidence regarding the association between tea intake and NAFLD risk is inconsistent. ObjectiveTo examine the genetically predicted causal association between tea intake and NAFLD risk using the two-sample Mendelian randomization (MR) method. MethodsSingle‐nucleotide polymorphisms (SNPs) strongly associated with tea intake were obtained from a large dataset (N = 447,485) in the UK biobank, and summary‐level genetic data for NAFLD (2,275 cases and 375,002 controls) were collected from the FinnGen consortium. The two-sample MR method was used to investigate the causal association between tea intake and NAFLD risk. The random‐effects inverse‐variance weighted (IVW) was used as the primary approach for estimating the causal effect, and MR Egger, weighted median, simple mode, and weighted mode were used to verify the robustness of the primary results. ResultsTwenty-four valid SNPs were selected as the instrumental variables for tea intake. The IVW results indicated that tea intake was not causally associated with NAFLD risk (Odds ratio: 1.48; 95 % confidence interval: 0.64, 3.43; p = 0.364); moreover, the results from other methods were consistent with this finding. A leave-one-out analysis further demonstrated the robustness of our results. No evidence of heterogeneity, outliers, or horizontal pleiotropy was found. ConclusionOur results do not support tea intake being causally associated with a decreased risk of NAFLD.

Non-alcoholic fatty liver disease: Genetic susceptibility

The prevalence of Non-alcoholic Fatty Liver Disease (NAFLD) is increasing, particularly in individuals who consume minimal to no alcohol. Currently, NAFLD affects at least 32% of the global population. Although not all but approximately 5-10% cases of NAFLD progress to non-alcoholic steatohepatitis (NASH), a condition arising from lipotoxicity. Patients with NASH may further develop liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). However, it is important to note that progression from NAFLD to NASH and HCC is not inevitable for all patients. The pathogenesis of HCC in the context of NAFLD and NASH remains poorly understood, however, fat accumulation, often due to obesity or metabolic syndrome, leads to lipotoxicity. In individuals with type 2 diabetes (T2D), elevated insulin levels promote lipolysis in adipose tissue and activate lipid-synthesizing enzymes such as fatty acid synthase (FAS) and stearoyl-CoA desaturase 1 (SCD1), which contribute to lipid accumulation in the liver. Additionally, high glucose levels in T2D can alter gene regulation by activating carbohydrate response-element binding protein (ChREBP) and insulin can increase the activity of sterol regulatory element binding protein (SREBP-1c). These lipogenic transcription factors are known to directly or indirectly activate patatin-like phospholipase domain-containing protein 3 (PNPLA3). Recent research has found elevated levels of angiotensinogen (AGT) and des-angiotensin in both experimental animals and patients with NAFLD. Emerging evidence highlights the significance of genetic factors in the risk of developing NAFLD. Here we explore the association between specific genes and hepatosteatosis, detailing the roles of T2D and obesity in the progression from NAFLD to NASH, and involvement of hepatic stellate cells in liver fibrosis. Additionally, we examine the impact of genes such as PNPLA3, MBOAT7, TM6SF2, GKRP, CCN3, and AGT as well as role of single nucleotide polymorphisms in gene regulation and their contribution to the risk of NAFLD.

Non-alcoholic fatty liver disease: A new predictor of recurrent ischemic stroke and transient ischemic attack in patients with carotid atherosclerosis

PurposeNon-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. This study focused on assessing the predictive significance of NAFLD for recurrent stroke and transient ischemic attack (TIA) risk to determine the value of NAFLD. MethodThis study included 742 participants (mean age: 64.26 ± 9.42 years, 497 males) with carotid atherosclerosis who underwent carotid CT angiography (CTA) between January 2013 and December 2021 in this retrospective study. NAFLD was diagnosed by non-enhanced abdominal CT. The clinical endpoint was a recurrent ischemic stroke or TIA. Cox proportional hazards and Kaplan-Meier analysis assessed whether NAFLD was associated with the endpoint. We accessed the predictive values of NAFLD, clinical, plaque characteristics, and combined model by the C statistics. The predictive performance of the combined model was assessed by receiver operating characteristic curve (ROC) analysis. ResultsA total of 742 participants (mean age: 64.26 ± 9.42 years, 497 males) were included. During 2.9 years of follow-up (interquartile range, 2.1–3.9), 166 patients reached the clinical endpoint. Multivariable cox analyses showed NAFLD was associated with recurrent stroke or TIA in all groups (all P<0.05). Patients with NAFLD had a lower event-free survival (EFS) rate than those without NAFLD (P<0.05). The combined model, including NAFLD, clinical data and plaque features, showed the best performance in predicting the clinical endpoint (AUC=0.79). ConclusionsNAFLD contributes to the prediction of recurrent ischemic stroke or TIA. NAFLD may be a novel imaging marker that offers a new perspective on preventing cardiovascular disease in the clinic.

Elevated Alanine Transaminase-to-Platelet Index (APRI) Is Associated with Obesity and Distinct Forms of Dyslipidemia: A Retrospective Cross-Sectional Study.

Background: Obesity is a pathological condition and a major risk factor for dyslipidemia, type 2 diabetes, and non-alcoholic fatty liver disease. Recent research highlighted the association of non-invasive serum markers with these conditions but the clinical utility of ALT APRI in obesity and its relationship with dyslipidemia remain unexplored. Methods: We examined the association of ALT APRI in 165 non-diabetic adults stratified by BMI and serum lipid parameters. Results: Obese subjects had significantly higher APRI than lean subjects, with an area under the curve (AUC) of 0.65 (p = 0.019). Medians of APRI were significantly increased in subjects with high TG, TG/HDL, TC/HDL, and LDL/HDL and low HDL. Notably, all lipid parameters and ratios were significantly elevated in the highest APRI tertile, compared with patients in the lowest tertile. APRI was weakly yet significantly correlated with BMI (R2 = 0.032, p = 0.022), HDL (R2 = 0.071), TG/HDL (R2 = 0.031), TC/HDL (R2 = 0.063), LDL/HDL (R2 = 0.072), and TyG index (R2 = 0.081). While APRI only showed a discriminating capacity for HDL (AUC: 0.69, p = 0.003), TG/HDL (AUC: 0.63, p = 0.020), LDL/HDL (AUC: 0.68, p < 0.001), and TyG index (AUC: 0.65, p = 0.037), the highest diagnostic performance of APRI was observed with TC/HDL (AUC: 0.74, p < 0.001). Additionally, APRI was a risk factor for high TG (OR: 1.6, p = 0.028), low HDL (OR: 2.7, p = 0.0002), high TG/HDL (OR: 1.94, p = 0.0011), high TC/HDL (OR: 2.3, p < 0.0001), high LDL/HDL (OR: 2.2, p = 0.0001), and high TyG index (OR: 2.1, p = 0.008). Conclusions: Our findings argue for the role of APRI as a potential marker for obesity and dyslipidemia, which requires further confirmation in longitudinal studies.

Factors Associated with Nonalcoholic Fatty Liver Disease in a Non-Overweight/Obese and Overweight/Obese Chinese Population at Risk for Metabolic Syndrome: A Cross-Sectional Multicenter Study

Factors Associated with Nonalcoholic Fatty Liver Disease in a Non-Overweight/Obese and Overweight/Obese Chinese Population at Risk for Metabolic Syndrome: A Cross-Sectional Multicenter Study

Mangiferin ameliorates polycystic ovary syndrome in rats by modulating insulin resistance, gut microbiota, and ovarian cell apoptosis.

Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder characterized by hyperandrogenism, prolonged anovulation and polycystic ovaries. However, there are no effective interventions to treat this disorder. As previously shown, mangiferin modulated the AMPK and NLRP3 signal pathways to alleviate nonalcoholic fatty liver disease (NAFLD). In recent years, mangiferin has emerged as a promising drug candidate for treating metabolic diseases. In this study, we evaluated the effects of mangiferin on a letrozole (LET) combined with high-fat diet (HFD)-induced PCOS rat model through estrous cycle detection, serum/tissue biochemical analysis, and hematoxylin and eosin (HE) staining of ovarian tissue. The mechanisms of mangiferin's effects on PCOS rats were analyzed using 16S rRNA sequencing, RNA-seq, western blotting (WB), and immunohistochemical (IHC) staining. Our results displayed that mangiferin showed a promising effect in PCOS rats. It improved lipid metabolism, glucose tolerance, insulin resistance, hormonal imbalance, ovarian dysfunction, and adipocyte abnormalities. RNA-seq analysis indicated that mangiferin may be involved in several signal pathways, including apoptosis, necrosis, and inflammation. Furthermore, western blot and immunohistochemical staining demonstrated that mangiferin regulates Caspase-3 and Cytc, exhibiting anti-apoptotic activity in the ovaries. Additionally, mangiferin significantly altered the gut microbiota community of PCOS rats, changing the abundance of firmicutes, bacteroidota, proteobacteria, and actinobacteria at the phylum level and the abundance of Blautia, Coprococcus, Roseburia, and Pseudomonas at the genus level. In conclusion, mangiferin is a promising and novel therapeutic agent for PCOS as it ameliorates insulin resistance, gut microbiota and ovarian cell apoptosis.