Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major cause of chronic liver disease and is closely linked to obesity and metabolic syndrome, necessitating efficient, non-invasive diagnostic tools. Methods: This monocentric cross-sectional study included 178 patients (69.1% with MASLD, 30.9% normal subjects; 55% males; mean age 52.79 ± 12.56 years) who underwent anthropometric and biochemical assessments to determine the visceral adiposity index (VAI), triglyceride-glucose index (TyG), and lipid accumulation product (LAP), along with abdominal ultrasound and vibration-controlled transient elastography (VCTE) with controlled attenuation parameter (CAP). Results: Patients were categorized based on steatosis severity: S0-S1 (n = 64) and S2-S3 (n = 114). The TyG, VAI, and LAP values were significantly higher in S2-S3 cases (p < 0.0001) and showed moderate-to-strong correlations with both steatosis and fibrosis. Predictive models yielded AUROCs of 0.80 (TyG), 0.83 (VAI), and 0.79 (LAP) for diagnosing S2-S3 steatosis. The NAFLD fibrosis score (NFS) and FIB-4 classified fibrosis severity, but 36.8% of cases remained unclassified. Applying the TyG and VAI thresholds reduced this rate to 26.3%. Conclusions: These findings support the TyG, VAI, and LAP as valuable non-invasive biomarkers for MASLD assessment, enhancing the classification accuracy when conventional fibrosis scores are inconclusive.

Nonalcoholic fatty liver disease (NAFLD) is a growing global health concern, impacting approximately 32.4% of the worldwide population. As a disease linked to metabolic dysfunction, NAFLD continues to rise alongside global increases in obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome. There is considerable evidence indicating that NAFLD disproportionately affects racial, ethnic, and minority groups, although the exact reasons for these disparities remain elusive. Contributing factors to this disease may include socioeconomic status, cultural influences, stress, genetic factors, and lifestyle choices. Emerging evidence suggests that these causal factors could influence epigenetic mechanisms, particularly DNA methylation and histone modifications, as well as the composition and diversity of gut microbiota. Nevertheless, there is a scarcity of research that comprehensively examines the interplay between epigenetic changes and gut microbiome variations in relation to NAFLD disparities across different racial and ethnic populations globally. This paper intends to (i) explore the connections between NAFLD, ethnic disparities, gut microbiota composition, and epigenetic alterations, while reviewing pertinent studies that illustrate how these factors contribute to health inequities among various ethnic groups impacted by this disease; (ii) explore potential therapeutic targets and biomarkers to advance the management of NAFLD; and (iii) provide insights to enhance our understanding of the mechanisms associated with this disease, thereby promoting further research in this field. Advancements in this area are anticipated to enhance our understanding of disease susceptibilities in at-risk groups and to provide new therapeutic options for NAFLD and its associated complications.

Metabolic-associated fatty liver disease (MAFLD), the most prevalent liver disorder globally, affects 20%-40% of the population and presents significant health challenges. Studies link MAFLD to male reproductive dysfunction, highlighting the need for effective interventions. This study investigates the impact of MAFLD on testicular function and evaluates the protective role of endurance training, with a focus on the GRP78-IRE-1α-ATF6 signaling pathway.

Forty-four rats were allocated into two dietary groups (n = 22 each): a standard diet control group (C) and a high-fat diet supplemented with fructose water group (FL). After 17 weeks, histological analysis confirmed MAFLD development in the FL group, while the control group showed no pathological changes. Each dietary group was further subdivided into sedentary and endurance-trained (T) subgroups (n = 10 per subgroup), resulting in four experimental groups: C, C + T, FL + T, and FL. At the end of the research, thyroid stimulating hormone (TSH), sex hormones (testosterone), tumor necrosis factor-alpha (TNF-a) as well as GRP78, IRE-1α, and AFT6 expression were assessed.

Our results indicated that MAFLD led to significant weight gain, disrupted serum levels of thyroid-stimulating hormone, and impaired sex hormone profile. Additionally, MAFLD triggered ER stress, evidenced by dysregulated expression of genes in the GRP78-IRE-1α-ATF6 pathway. Remarkably, endurance training mitigated these adverse effects by normalizing hormonal profiles and restoring the expression of ER stress-related genes. These findings highlight the critical role of ER stress in MAFLD-induced male reproductive dysfunction.

Overall, the present study suggests endurance training as a promising treatment strategy for addressing MAFLD and its associated reproductive complications.

Background: Nonalcoholic fatty liver disease (NAFLD) has a major impact on public health owing to its high morbidity and mortality due to its close relationship with several conditions, including metabolic syndrome, cirrhosis, and cancer. Therefore, this review aimed to systematically compile and summarize the scientific literature on early risk factors for NAFLD development. Methods: A systematic review of population-based cohort studies was conducted. Studies reporting the risk factors associated with nonalcoholic steatohepatitis (NASH) and NAFLD were screened. Results: The search yielded 987 unique records, of which 196 articles were selected after title and abstract screening. A total of 39 articles were read in full text after quality analysis using Downs and Black criteria; 10 of the studies were excluded due to heterogeneity or inconclusive results. Finally, 30 publications were included in this systematic review. The review revealed that clinical conditions such as obesity, weight change, psoriasis, polycystic ovary syndrome, diabetes, thyroid disorders, and elevated serum uric acid levels increase the risk of developing nonalcoholic fatty liver. In addition, lifestyle factors such as sedentary behavior, active or passive smoking, poor sleep quality, and consumption of carbonated beverages are associated with this condition. Conclusions: Evidence was found on the association between different clinical and lifestyle risk factors and NAFLD. This supports the need for preventive, diagnostic, and therapeutic strategies to improve the metabolic, hepatic, and oncological outcomes related to this condition.

Nonalcoholic fatty liver disease (NAFLD) manifests as chronic hepatic steatosis, occurring variably across people due to racial and genetic diversity. It represents a stage in the development of chronic liver disease, marked by fat accumulation, inflammatory responses, oxidative stress in the endoplasmic reticulum, and fibrosis as primary concerns. Understanding its underlying mechanisms remains a challenging and pivotal area of study. In the past, acute liver injury-related diseases were commonly treated with methods such as liver transplantation. However, the emergence of artificial liver has shifted focus to stem cell therapies. Unlike conventional drugs, stem cell therapies are continuously evolving. Despite being classified as drugs, stem cells demonstrated significant efficacy after multiple injections. Mesenchymal stem cells, unlike other types of stem cells, do not have the risk of tumor formation and low immunogenicity, reducing the hypersensitivity reactions associated with liver transplantation. Increasingly, studies suggest that mesenchymal stem cells hold promise in the treatment of chronic liver injury diseases. This review focuses on investigating the role of mesenchymal stem cells in chronic metabolic liver diseases, such as non-alcoholic fatty liver disease, and delves into their specific functions.

The gut microbiota (GM) is a highly dynamic ecology whose density and composition can be influenced by a wide range of internal and external factors. Thus, "How do GM, which can have commensal, pathological, and mutualistic relationships with us, affect human health?" has become the most popular research issue in recent years. Numerous studies have demonstrated that the trillions of microorganisms that inhabit the human body can alter host physiology in a variety of systems, such as metabolism, immunology, cardiovascular health, and neurons. The GM may have a role in the development of a number of clinical disorders by producing bioactive peptides, including neurotransmitters, short-chain fatty acids, branched-chain amino acids, intestinal hormones, and secondary bile acid conversion. These bioactive peptides enter the portal circulatory system through the gut-liver axis and play a role in the development of chronic liver diseases, cirrhosis, and hepatic encephalopathy. This procedure is still unclear and quite complex. In this study, we aim to discuss the contribution of GM to the development of liver diseases, its effects on the progression of existing chronic liver disease, and to address the basic mechanisms of the intestinal microbiota-liver axis in the light of recent publications that may inspire the future.

The increased consumption of dietary fats contributes to the development of MAFLD (metabolic fatty liver disease). The ability of broccoli to enhance lipid metabolism has attracted researchers' attention. Researchers fed C57BL/6 mice a 12-week HFD to ensure the induction of MAFLD. The findings indicated that broccoli floret juice could effectively relieve MAFLD. Broccoli is helpful for reducing weight, blood glucose levels, fat accumulation, and insulin resistance associated with MAFLD and reduces the concentrations of TC, TG, LDL-C, GOT, GPT, IL-1β, IL-6, CCL4, and MCP1. Broccoli can increase the concentration of HDL-C, CAT, GSH-Px, SOD, and T-AOC, relieve inflammation and hepatic and ileum damage, and improve the antioxidant capacity of the body. Also, broccoli can optimize the structure of intestinal flora, promote the growth of Allobaculum, Muribaculaceae, Akkermansia, Eubacterium, and Bacteroides, and reduce bile acid deposition. In addition, the FXR/LXRα signaling system is impacted by broccoli, which is capable of raising the average levels of expression of the Fxr, SHP, and Cyp7a1 genes and proteins and reducing those of the genes for Fasn, Lpin 1, Dgat 2, Scd1, LXRα, and SREBP-1c.

Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease worldwide, with liver fibrosis (LF) being a crucial pathological feature in the progression of NAFLD. Insulin resistance (IR) is believed to play an important role in the pathogenesis of NAFLD and the development of LF. This study aims to explore the relationship between various IR indicators and LF in patients with NAFLD.

This study utilized data from the National Health and Nutrition Examination Survey 2017-2020 cycles. Liver steatosis and fibrosis were assessed using liver ultrasound transient elastography. To assess the association between multiple IR indicators and LF, the study methodology included univariate and multivariate logistic regression, as well as restricted cubic spline (RCS) analysis. Subsequently, we used multivariate logistic regression to develop and validate a predictive model for LF, and evaluated the model's performance using the area under the curve (AUC) and calibration curve.

A total of 904 patients were included in the final analysis. Among these NAFLD patients, 153 (16.92%) had LF. Compared to non-LF patients, LF patients had significantly higher body mass index (BMI), waist circumference (WC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), HbA1c, and fasting blood glucose (FBG) levels (all p < 0.05). Analysis of IR indicators showed that LF patients had significantly higher levels of TyG, TyG-WHtR, TyG-BMI, TyG-WC, TyG-GGT, METS-IR, and HOMA-IR (all p < 0.05). After adjusting for covariates, TyG-WHtR remained an independent risk factor (OR=2.69; 95% CI: 2.08-3.47), indicating a strong correlation with LF. The developed nomogram, incorporating AST, TyG, TyG-BMI, and diabetes, showed an AUC of 0.809 (95% CI: 0.771-0.847), indicating good predictive performance for LF in NAFLD patients.

This study confirms that a significant association between various IR and LF in NAFLD patients, and the developed nomogram provides a practical tool for early risk assessment. These findings underscore the clinical value of incorporating IR indices into routine practice to identify high-risk patients, enabling timely interventions to prevent fibrosis progression and improve outcomes.

Peroxisomes are crucial for fatty acid β-oxidation in steatosis, but the role of pexophagy-the selective autophagy of peroxisomes-remains unclear. This study investigated the effects of the peroxisome proliferator-activated receptor-α (PPARα) agonist clofibrate on pexophagy in a coconut oil-based high-fat diet (HFD)-induced hepatocarcinogenesis model. Rats were divided into four groups: control, clofibrate, HFD, and HFD with clofibrate. The HFD induced steatosis, along with a 2.4-fold increase in pexophagy receptor NBR1-positive granules in hepatocytes. Clofibrate significantly inhibited HFD-induced steatosis, increasing p62-, LAMP2-, and Pex5-positive granules by 7.5-, 7.2-, and 71.4-fold, respectively, while decreasing NBR1 expression. The effects were associated with peroxisome proliferation and pexophagy in ultrastructural observations and increased levels of Lc3, p62, Pex2, Pex14, Acox1, and Scd1 in gene expression analysis. The results suggested that clofibrate effectively reduced steatosis through combined peroxisome proliferation and pexophagy, though it had a marginal impact on hepatocarcinogenesis in coconut oil-based HFD-fed rats. These findings highlight the utility of PPARα agonists in studying mammalian pexophagy.

Goose fatty liver (or foie gras) does not develop inflammation even in severe steatosis, which is different from human nonalcoholic fatty liver disease (NAFLD), and it is considered as a unique model for NAFLD study. The deubiquitinating enzyme, Ovarian Tumor (OTU)-Deubiquitinase 1 (OTUD1), is involved in various cell biological processes by regulating the expression of cytokines. Its role and mechanism in the formation of goose fatty liver however are not clear yet. This study determined the expression of OTUD1 in goose fatty liver versus normal liver and OTUD1 expression in goose primary liver treated with glucose, fatty acids and insulin using qPCR and immunoblotting assays. OTUD1 gene overexpression and subsequent transcriptome sequencing analysis were performed to identify the differentially expressed genes (DEG) and the pathways where the DEGs are enriched. Immunoprecipitation and protein mass spectrometry were employed to screen the interacting proteins of OTUD1. The results showed that both the mRNA and protein abundances of OTUD1 in goose fatty liver were higher than those of normal liver. In goose primary hepatocytes, palmitic acid and oleic acid both increased the protein levels of OTUD1, while glucose and insulin inhibited the expression of the protein. Overexpression of OTUD1 significantly affected the expression of genes and pathways related to inflammatory/immune responses and cell growth/death. The interacting proteins of OTUD1 are mainly related to membrane transport, immune/inflammatory response, ubiquitination and signaling pathways. The interaction between OTUD1 and AP1G1 was validated by co-immunoprecipitation and immunoblotting assays. Consistently, the relative ubiquitination level of AP1G1 in goose fatty liver was lower than that of normal liver, which is correlated with increased protein abundance of AP1G1 and OTUD1 in goose fatty liver. In conclusion, the increased protein abundance of OTUD1 in goose fatty liver can regulate the expression of cytokines and related pathways during the formation of goose fatty liver by promoting the deubiquitination of the interacting proteins of OTUD1, including AP1G1.

Mendelian Randomization studies indicate that BMI contributes to various diseases, but it's unclear if this is entirely mediated by BMI itself. This study examines whether disease risk from BMI-associated sequence variants is mediated through BMI or other mechanisms, using data from Iceland and the UK Biobank. The associations of BMI genetic risk score with diseases like fatty liver disease, knee replacement, and glucose intolerance were fully attenuated when conditioned on BMI, and largely for type 2 diabetes, heart failure, myocardial infarction, atrial fibrillation, and hip replacement. Similar attenuation was observed for chronic kidney disease and stroke, though results varied. Findings were consistent across sexes, except for myocardial infarction. Residual effects may result from temporal BMI changes, pleiotropy, measurement error, non-linear relationships, non-collapsibility, or confounding. The attenuation extent of BMI genetic risk score on disease associations suggests the potential impact of reducing BMI on disease risk.

Background/Objective: Long-term intake of a high-fat diet (HFD) leads to obesity and gut dysbiosis. AMP-activated protein kinase (AMPK) is a key regulator of energy metabolism. Herein, we investigated the impacts of Lactobacillus (Lactiplantibacillus) plantarum P111 and Bifidobacterium longum P121, which suppressed dexamethasone-induced adipogenesis in 3T3 L1 cells and increased lipopolysaccharide-suppressed AMPK activation in HepG2 cells, on HFD-induced obesity, liver steatosis, gut inflammation and dysbiosis, and depression/cognitive impairment (DCi)-like behavior in mice. Methods: Obesity is induced in mice by feeding with HFD. Biomarker levels were measured using immunoblotting, enzyme-linked immunosorbent assay, and immunofluorescence staining. Results: Orally administered P111, P121, or their mix LpBl decreased HFD-induced body weight gain, epididymal fat pad weight, and triglyceride (TG), total cholesterol (TC), and lipopolysaccharide levels in the blood. Additionally, they downregulated HFD-increased NF-κB activation and TNF-α expression in the liver and colon, while HFD-decreased AMPK activation was upregulated. They also suppressed HFD-induced DCi-like behavior and hippocampal NF-κB activation, NF-κB-positive cell population, and IL-1β and TNF-α levels, while increasing the hippocampal BDNF-positive cell population and BDNF level. The combination of P111 and P122 (LpBl) also improved body weight gain, liver steatosis, and DCi-like behavior. LpBl also mitigated HFD-induced gut dysbiosis: it decreased Desulfovibrionaceae, Helicobacteriaceae, Coriobacteriaceae, and Streptococcaceae populations and lipopolysaccharide production, which were positively correlated with TNF-α expression; and increased Akkermansiaceae, Bifidobacteriaceae, and Prevotellaceae populations, which were positively correlated with the BDNF expression. Conclusions: P111 and/or P121 downregulated adipogenesis, gut dysbiosis, and NF-κB activation and upregulatde AMPK activation, leading to the alleviation of obesity, liver steatosis, and DCi.

Sarcopenia increases the risk of nonalcoholic steatohepatitis (NASH) and cirrhosis in patients with nonalcoholic fatty liver disease (NAFLD). Subsequently, poorly managed NAFLD can result in adverse health outcomes. Lifestyle interventions are effective for both NAFLD and sarcopenia; however, diagnosis of sarcopenia in this population is not well defined. This review aimed to examine current methods to diagnose sarcopenia in NAFLD patients.

MEDLINE, EMBASE, and CINAHL databases were searched for articles published until July 2023 using the terms "Non-alcoholic fatty liver disease," "NAFLD," "fatty liver," "sarcopenia," and "myoatrophy." Studies were excluded if they included pediatric populations, did not diagnose both sarcopenia and NAFLD, or included patients with alternate causes of liver disease.

Twenty studies, predominantly from Asian countries (14 [70.0%]), involving 68 848 participants (45.5% females) were included. In 15 studies, most participants had a BMI > 25 kg/m2. Heterogeneity in the tools used to diagnose NAFLD was identified, with abdominal ultrasound being the most commonly used. European, Asian, and Australasian Sarcopenia Working Groups had differing diagnostic definitions of sarcopenia. Of the three potential diagnostic elements of sarcopenia (muscle mass, strength, function), all studies measured muscle mass, commonly through bioelectrical impedance analysis (12 [60.0%]). Seven studies (35.0%) measured muscle strength, with the majority (n = 6) utilizing hand grip strength. Four (20.0%) measured muscle function, through gait speed or a timed up-and-go test.

The lack of standardization in sarcopenia diagnosis for NAFLD patients is concerning. A consistent definition is necessary to prevent this comorbidity from being overlooked, improve care, and outcomes.

Studies on the prevalence of nonalcoholic steatohepatitis (NASH) and the factors associated with its high prevalence among Iranian people are limited. This study evaluated the prevalence of NASH and its associated factors among Iranian adults using Pars Cohort Study (PCS) data.

This cross-sectional study was conducted based on PCS, which includes 40-75-year-old adults from the Valashahr area. NASH was defined as alanine aminotransferase (ALT) higher than 40 U/L without evidence of hepatitis B or C infections. The prevalence of NASH and its associations with basic and demographic characteristics, socioeconomic characteristics, medical history, gastrointestinal symptoms, and laboratory tests were evaluated.

Overall, 8734 patients, including 3917 men (44.8%), were enrolled in this study. The mean age of participants was 52.62 years (SD=9.68), and 605 individuals had NASH (6.9%). In the regression analysis, in contrast to female gender (OR=0.31, 95% CI=0.249‒0.386, P<0.001) and age (OR=0.951, 95% CI=0.941‒0.962, P<0.001), history of heart disease (OR=1.499, 95% CI=1.146‒1.962, P=0.003), history of diabetes (OR=1.523, 95% CI=1.162‒1.995, P=0.002), hypertension (OR=1.241, 95% CI=1.023‒1.506, P=0.029), being overweight or obese (OR=2.192, 95% CI=1.755‒2.737, P<0.001), being in the richest or second richest wealth index quantiles (OR=1.315, 95% CI=1.107‒1.156, P=0.002), and increased waist circumference (OR=1.409, 95% CI=1.107‒1.793, P<0.005) were independently associated with a higher risk of having NASH.

In this study, we determined the prevalence of NASH and found male gender, younger age, history of heart disease, history of diabetes, hypertension, socioeconomic status, and obesity as possible factors associated with a higher risk of NASH among Iranians.

Ferroptosis, a form of regulated cell death characterized by lipid peroxidation and iron accumulation, has been implicated in the progression of metabolic-dysfunction-associated steatohepatitis (MASH) in obesity. This study investigated the role of ferroptosis in the development of hepatic steatosis and MASH in obese mice and assessed the therapeutic potential of ferrostatin-1, a ferroptosis inhibitor. C57BL/6J wild-type (n = 8) and ob/ob mice (n = 16) were maintained on a standard chow diet. Mice were divided into three groups that included C57BL/6 (n = 8), ob/ob (n = 8), and ob/ob + ferrostatin-1 (FER) (n = 8), with the latter group receiving an intraperitoneal injection of 5 μM/kg ferrostatin three times per week for eight weeks. Following treatment, serum and tissue samples were collected for analysis. Significant hepatic steatosis and increased lipogenesis markers were observed in ob/ob mice, which were restored to baseline levels in the ob/ob + FER group treated with ferrostatin-1. Elevated oxidative stress was indicated by increased reactive oxygen species (ROS) and malondialdehyde (MDA) levels in the ob/ob group, while glutathione peroxidase 4 (GPX4) activity was significantly reduced. Ferrostatin-1 treatment decreases MDA levels and restores GPX4 activity. Additionally, ferrostatin mitigates iron overload and promotes macrophage polarization from M1 to M2, thereby reducing liver inflammation and fibrosis. Ferrostatin treatment reversed mitochondrial dysfunction in ob/ob mice. Our findings revealed that ferroptosis plays a significant role in the progression of obesity to hepatic steatosis and MASH. Inhibiting ferroptosis using ferrostatin-1 effectively improves liver histology, reduces oxidative stress, normalizes lipogenesis, and modulates macrophage polarization. This study highlights the potential of targeting ferroptosis as a therapeutic strategy for obesity-related liver diseases, warranting further investigation in clinical settings.

Aim: Nonalcoholic fatty liver disease (NAFLD) is a significant health issue worldwide. This study investigated the effect of the adiponectin receptor 1 gene (ADIPOR1) polymorphism on susceptibility to NAFLD.Methods: Data from 330 participants, including 165 biopsy-proven NAFLD patients and 165 healthy controls, were collected. The PCR-RFLP method was used to detect the genotypes of ADIPOR1 rs2275738 or T-106C variant.Results: The "CC" genotype of the ADIPOR1 rs2275738 polymorphism, compared with the "TT" genotype and the "C" allele, compared with the "T" allele, are markers of increased NAFLD susceptibility (p = 0.018; OR = 2.07, 95% CI = 1.43-2.01 and p = 0.041; OR = 1.52, 95% CI = 1.24-2.35, respectively).Conclusion: This research suggests, for the first time, that the ADIPOR1 rs2275738 "CC" genotype is associated with a 107% increased risk for biopsy-proven NAFLD.

Our study aims to map the trends in obesity prevalence over the past four years and to describe the health, behavior, and psychological factors of people living with obesity in Saudi.

This is a secondary data analysis using the Sharik Health Indicators Surveillance System (SHISS) from 2020 to 2023. The SHISS dataset comprises cross-sectional telephone interviews carried out quarterly across all administrative regions of Saudi Arabia. Recruitment of participants was restricted to Saudi resident adults only.

The study analyzed data from 92,137 participants, with a balanced region and gender distribution. The average age of participants was 36.83 ± 13.68 years. The prevalence of obesity showed minor fluctuations over four years, with the highest at 22.2% in 2020 and lowest at 21.4% in 2023. This study showed that a slight decline in daily smoking rates was observed from 2020 to 2023 across all categories. Participants living with obesity reported a higher consumption of fruits and vegetables compared to their not with obesity counterparts. In addition, participants living with obesity engaged less frequently in physical activities compared to those without obesity. Moreover, people living with obesity have higher incidence rates of depression and anxiety, as well as various of chronic diseases.

This study highlights the complex factors affecting obesity prevalence in Saudi Arabia. Despite progress, ongoing health promotion and disease prevention are crucial to address the persistent challenges driven by behavioral and socio-economic factors. Continued surveillance and longitudinal studies are essential to track trends in obesity, smoking, and physical activity, ensuring that health initiatives align with population needs.

Background and Objectives: Metabolic syndrome (MetS) is a condition marked by a complex array of physiological, biochemical, and metabolic abnormalities, including central obesity, insulin resistance, high blood pressure, and dyslipidemia (characterized by elevated triglycerides and reduced levels of high-density lipoproteins). The pathogenesis develops from the accumulation of lipid droplets in the hepatocyte (steatosis). This accumulation, in genetically predisposed subjects and with other external stimuli (intestinal dysbiosis, high caloric diet, physical inactivity, stress), activates the production of pro-inflammatory molecules, alter autophagy, and turn on the activity of hepatic stellate cells (HSCs), provoking the low grade chronic inflammation and the fibrosis. This syndrome is associated with a significantly increased risk of developing type 2 diabetes mellitus (T2D), cardiovascular diseases (CVD), vascular, renal, pneumologic, rheumatological, sexual, cutaneous syndromes and overall mortality, with the risk rising five- to seven-fold for T2DM, three-fold for CVD, and one and a half-fold for all-cause mortality. The purpose of this narrative review is to examine metabolic syndrome as a "systemic disease" and its interaction with major internal medicine conditions such as CVD, diabetes, renal failure, and respiratory failure. It is essential for internal medicine practitioners to approach this widespread condition in a "holistic" rather than a fragmented manner, particularly in Western countries. Additionally, it is important to be aware of the non-invasive tools available for assessing this condition. Materials and Methods: We conducted an exhaustive search on PubMed up to July 2024, focusing on terms related to metabolic syndrome and other pathologies (heart, Lung (COPD, asthma, pulmonary hypertension, OSAS) and kidney failure, vascular, rheumatological (osteoarthritis, rheumatoid arthritis), endocrinological, sexual pathologies and neoplastic risks. The review was managed in accordance with the PRISMA statement. Finally, we selected 300 studies (233 papers for the first search strategy and 67 for the second one). Our review included studies that provided insights into metabolic syndrome and non-invasive techniques for evaluating liver fibrosis and steatosis. Studies that were not conducted on humans, were published in languages other than English, or did not assess changes related to heart failure were excluded. Results: The findings revealed a clear correlation between metabolic syndrome and all the pathologies above described, indicating that non-invasive assessments of hepatic fibrosis and steatosis could potentially serve as markers for the severity and progression of the diseases. Conclusions: Metabolic syndrome is a multisystem disorder that impacts organs beyond the liver and disrupts the functioning of various organs. Notably, it is linked to a higher incidence of cardiovascular diseases, independent of traditional cardiovascular risk factors. Non-invasive assessments of hepatic fibrosis and fibrosis allow clinicians to evaluate cardiovascular risk. Additionally, the ability to assess liver steatosis may open new diagnostic, therapeutic, and prognostic avenues for managing metabolic syndrome and its complications, particularly cardiovascular disease, which is the leading cause of death in these patients.

Background Metabolism dysfunction-associated steatotic liver disease (MASLD) is hepatic steatosis along with increased weight or obesity, type 2 diabetes, or metabolic dysregulation and without significant alcohol consumption. The clinical prediction of MASLD using simple, non-invasive indices like Fatty Liver Index (FLI), NAFLD Liver Fat Score (NAFLD LFS), Visceral Adiposity Index (VAI), Steato Test and Hepatic Steatosis Index (HSI) yielded heterogeneous results in different populations. Aim  We aimed to compare five scores (Fatty Liver Index, NAFLD Liver Fat Score, Visceral Adiposity Index, Steato Test, Hepatic Steatosis Index) for prediction of liver steatosis. Method Patients with metabolic syndrome and alcohol intake less than 20 grams per day were included in the study. Patients with alcohol intake greater than 20 grams per day and known history of liver or biliary disease, infections, muscle injury, autoimmune diseases, thyroid disorders, underlying secondary diabetes mellitus, secondary hypertension, familial dyslipidemia, intake of medications like steroids, hepatotoxic drugs, chemotherapy or drugs altering liver function tests were excluded. The presence of fatty liver was confirmed on ultrasound. Five indices (Fatty Liver Index, NAFLD Liver Fat Score, Visceral Adiposity Index, Steato Test, Hepatic Steatosis Index) were applied to predict liver steatosis. The correlation of each index with presence of fatty liver was analyzed. Based on the sensitivity of the five scoring systems and prevalence of MASLD as observed in existing literature, with a 95% confidence interval and 20% allowable error, the minimum number of positive cases required is 24 and minimum sample size required is 77. Results Among 100 (100%) patients with metabolic syndrome, MASLD was seen in 65 patients (74% males, 56% females). The mean age of patients with MASLD was 59 years. Fatty Liver Index, NAFLD Liver Fat Score, Visceral Adiposity Index, Steato Test had statistically significant (p<0.005) correlation with fatty liver on ultrasound of abdomen. Fatty Liver Index had the highest Area Under the Receiver Operating Characteristic curve (AUROC) of 0.65 (Sensitivity=63, Specificity=62.9%), followed by NAFLD Liver Fat Score (AUROC=0.63, Sensitivity=64.4%, Specificity=62.9%), Visceral Adiposity Index (AUROC=0.628, Sensitivity=50.8%, Specificity=65.7%) and Steato Test (AUROC=0.61, Sensitivity=46.2%, Specificity=77%). Cut-offs for Fatty Liver Index, NAFLD Liver Fat Score, Visceral Adiposity Index, and Steato Test were 42, 0.5, 4, and 4.5 respectively. MASLD was present in 71.4% (N=35) of patients with type 2 diabetes mellitus and 58.8% (N=30) without type 2 diabetes mellitus. Conclusion Fatty Liver Index, NAFLD Liver Fat Score, Visceral Adiposity Index, and Steato Test were comparable as early markers to predict liver steatosis in patients with metabolic syndrome.

The stage of life at the onset of obesity is an important factor in assessing inflammatory state and cardiometabolic risk.

This study aimed to evaluate the relationship between the obesity onset and the inflammatory profile in women with severe obesity.

Public hospital, Brazil.

Forty-eight women with severe obesity (20-59 yr old) were evaluated according to weight, height, neck circumference (NC), waist circumference (WC), and hip circumference, as well blood metabolic and inflammatory parameters. The participants were grouped according to obesity onset stage of life (early group: ≤19 yr; late group: >19 yr).

The demographic means of the participants were: age of 39.7 years, weight of 122.7 kg and body mass index (BMI) of 48.4 kg/m2. The late group presented significantly higher values of leptin (lep)/adiponectin (adipo) ratio and homeostatic model assessment for insulin resistance (HOMA-IR) than the early group. The late group also had a lower adipo/lep ratio. Moreover, the late group showed correlations between the lep/adipo ratio and BMI (r = .460, P = .021), NC (r = .478, P = .016), and WC (r = .535, P = .006). Adipo was also correlated with NC (r = -.418, P = .038), WC (r = -.437, P = .029), and glycated hemoglobin (HbA1C) (r = -.485, P = .019). By contrast, in the early group, the lep/adipo ratio showed correlations with insulin (r = .647, P = .004) and HOMA-B (r = .564, P = .015).

The inflammatory profile is correlated with anthropometric values in women with late-onset obesity. Inflammatory markers seemed to correlate with the glycemic profile in women with early-onset obesity. Furthermore, inflammation was higher in women with late-onset obesity compared to those with early-onset obesity.

Copper functions as an essential micronutrient influencing diverse metabolic processes in mammals, encompassing oxidative stress responses, lipid metabolism, and participation in enzymatic reactions. However, the impact of serum copper on non-alcoholic fatty liver disease (NAFLD) remains controversial. Our aim was to explore the precise correlation between serum copper and NAFLD in a large-scale population-based study. A total of 1377 participants from the National Health and Nutrition Examination Survey (NHANES) 2011-2016 were included in our study. The diagnosis of NAFLD and its progress to advanced liver fibrosis were based on serological indexes. One-way ANOVA, Kruskal-Wallis H test, and Chi-square test were used to access variations between quartiles groups of serum copper. We conducted multivariate-adjusted logistic regression models and subgroup analyses to investigate the association between serum copper and NAFLD, along with several metabolic diseases. Among the 1377 participants, 661 were diagnosed with NAFLD, and 141 of whom were classified into advanced liver fibrosis. Higher serum copper levels (≥ 21.00 μmol/L) were associated with an increased incidence of NAFLD (odds ratio (OR) = 2.07 (1.38-3.10), p < 0.001), as well as advanced liver fibrosis (OR = 2.40 (1.17-5.19), p = 0.025). Moreover, serum copper exhibited a positive correlation with hypertension, overweight, and abdominal obesity, all of which have been identified as risk factors of NAFLD. Additionally, female participants, under the age of 60, and with a higher body mass index (BMI) (> 24.9 kg/m2) emerged as the most vulnerable subgroup concerning the relationship between serum copper and NAFLD. In the U.S. population, a notable association has been identified, linking elevated serum copper to an increased susceptibility for both the onset and progression of NAFLD, along with several metabolic disorders associated with NAFLD. The adverse effects of excess copper warrant attention in the context of public health considerations.

Metabolic-associated fatty liver disease (MAFLD) is one of the most common liver diseases worldwide; however, its pathogenesis and treatment methods have not been perfected. NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) is a promising therapeutic target for MAFLD. Diosgenin (DG) is a natural compound that was identified in a traditional Chinese herbal medicine, which has pharmacological effects, such as anti-inflammatory, antioxidant, hepatoprotective, and hypolipidemic activities. In this study, we examined the effects and molecular mechanisms of DG on MAFLD in vitro and in vivo. We established a rat model by administering a high-fat diet (HFD). We also generated an in vitro MAFLD model by treating HepG2 cells with free fatty acids (FFAs). The results indicated that DG attenuated lipid accumulation and liver injury in both in vitro and in vivo models. DG downregulated the expression of NLRP3, apoptosis-associated speckle-like protein (ASC), cysteinyl aspartate specific proteinase-1 (caspase-1), gasdermin D (GSDMD), GSDMD-n, and interleukin-1β (IL-1β). In addition, we silenced and overexpressed NLRP3 in vitro to determine the effects of DG on antiMAFLD. Silencing NLRP3 enhanced the effect of DG on the treatment of MAFLD, whereas NLRP3 overexpression reversed its beneficial effects. Taken together, the results show that DG has a favorable effect on attenuating MAFLD through the hepatic NLRP3 inflammasome-dependent signaling pathway. DG represents a natural NLRP3 inhibitor for the MAFLD treatment.

To compare hepatic stiffness and fat fraction in patients with obesity and type 1 diabetes (T1D) with type 2 diabetes (T2D) with a similar body mass index (BMI).

In this prospective cross-sectional study, 90 participants with T1D (BMI 30.5 ± 4.5 kg/m2; diabetes duration 20.5 ± 9.8 years; HbA1c 8.2% ± 1.4%) and 69 with T2D (BMI: 30.8 ± 4.6 kg/m2; diabetes duration: 11.7 ± 7.8 years; HbA1c: 7.3% ± 1.4%) were included. Liver fat fraction and stiffness were examined by magnetic resonance imaging and elastography, respectively. Logistic regressions were used to evaluate associations with biomedical variables.

The mean liver stiffness score in patients with obesity and T1D was 2.2 ± 0.5 kPa, while in T2D it was 2.6 ± 0.8 kPa (P < .001). The liver fat fraction in patients with obesity and T1D was 3.7% ± 6.3%, and in T2D it was 10.6% ± 7.9% (P < .001). Metabolic dysfunction-associated steatotic liver disease (MASLD) was present in 13.3% of patients with T1D and in 69.6% of patients with T2D, whereas fibrosis was suggested in 7.8% of patients with T1D and in 27.5% of patients with T2D. Liver stiffness was four times higher in patients with T2D compared with those with T1D (odds ratio = 5.4, 95% confidence interval: 2.1-13.6, P < .001). Aspartate transaminase (AST), alanine transaminase, gamma-glutamyl transferase (GGT), triglycerides and the android-to-gynoid ratio were associated with elevated fat fraction in both cohorts. AST and GGT were associated with elevated liver stiffness in both cohorts.

Patients with obesity and T1D had lower liver fat and liver stiffness compared with those patients with T2D, despite similar levels of BMI, a longer duration of diabetes and worse glycaemic control.

Obesity is a significant risk factor for metabolic-associated steatotic liver disease (MASLD). The association between Helicobacter pylori (HP) infection and liver fibrosis has not been fully elucidated in patients with obesity and MASLD.

This observational retrospective study included clinical and biochemical parameters of patients with obesity undergoing bariatric surgery. HP infection was confirmed by gastric endoscopy, and liver biopsies were performed during surgery. Bivariate and logistic regression analyses were employed to evaluate independent associations with liver fibrosis and steatosis by biopsy.

The mean age of the subjects was 42 ± 10 years, with 84.7% being women, and they had a mean BMI of 42.97 ± 7.56 kg/m2. Overall, 41.7% of patients had an HP infection. Multiple logistic regression models were conducted to assess the association between HP infection, liver steatosis, and fibrosis by biopsy. HP infection was independently associated with liver fibrosis [OR = 3.164 (95% CI 1.011-9.900)].

Biopsy findings associated HP infection with increased liver fibrosis.

Nonalcoholic fatty liver disease (NAFLD) is a mainstream halting liver disease with high prevalence in North America, Europe, and other world regions. It is an advanced form of NAFLD caused by the amassing of fat in the liver and can progress to the more severe form known as non-alcoholic steatohepatitis (NASH). Until recently, there was no authorized pharmacotherapy reported for NASH, and to improve the patient's metabolic syndrome, the focus is mainly on lifestyle modification, weight loss, ensuring a healthy diet, and increased physical activity; however, the recent approval of Rezdiffra (Resmetirom) by the US FDA may change this narrative. As per the reported studies, there is an increased articulation of uptake and efflux transporters of the liver, including OATP and MRP, in NASH, leading to changes in the drug's pharmacokinetic properties. This increase leads to alterations in the pharmacokinetic properties of drugs. Furthermore, modifications in Cytochrome P450 (CYP) enzymes can have a significant impact on these properties. Xenobiotics are metabolized primarily in the liver and constitute liver enzymes and transporters. This review aims to delve into the role of metabolism, transport, and potential herb-drug interactions in the context of NASH.

Soldiers of the Mexican Army with obesity were subjected to an intense 60-day weight-loss course consisting of a controlled diet, daily physical training, and psychological sessions. The nutritional treatment followed the European Society of Cardiology (ESC) recommendations, incorporating elements of the traditional milpa diet in the nutritional intervention. The total energy intake was reduced by 200 kcal every 20 days, starting with 1,800 kcal and ending with 1,400 kcal daily. On average, the participants reduced their body weight by 18 kg. We employed an innovative approach to monitor the progress of the twelve soldiers who completed the entire program. We compared the untargeted metabolomics profiles of their urine samples, taken before and after the course. The data obtained through liquid chromatography and high-resolution mass spectrometry (LC-MS) provided insightful results. Classification models perfectly separated the profiles pre and post-course, indicating a significant reprogramming of the participants' metabolism. The changes were observed in the C1-, vitamin, amino acid, and energy metabolism pathways, primarily affecting the liver, biliary system, and mitochondria. This study not only demonstrates the potential of rapid weight loss and metabolic pathway modification but also introduces a non-invasive method for monitoring the metabolic state of individuals through urine mass spectrometry data.

The emergence of inflammatory diseases is a heavy burden on modern societies. Cannabis has been used for several millennia to treat inflammatory disorders such as rheumatism or gout. Since the characterization of cannabinoid receptors, CB1 and CB2, the potential of cannabinoid pharmacotherapy in inflammatory conditions has received great interest. Several studies have identified the importance of these receptors in immune cell migration and in the production of inflammatory mediators. As the presence of the CB2 receptor was documented to be more predominant in immune cells, several pharmacological agonists and antagonists have been designed to treat inflammation. To better define the potential of the CB2 receptor, three online databases, PubMed, Google Scholar and clinicaltrial.gov, were searched without language restriction. The full texts of articles presenting data on the endocannabinoid system, the CB2 receptor and its role in modulating inflammation in vitro, in animal models and in the context of clinical trials were reviewed. Finally, we discuss the clinical potential of the latest cannabinoid-based therapies in inflammatory diseases.

Non-alcoholic steatohepatitis (NASH) is a fatty liver disease that is not caused by alcohol consumption and is characterized by fatty degeneration, inflammation and hepatocellular damage. Therefore, predicting future fibrosis is critical in the early stages of NASH to prevent disease progression. The present study examined histological changes in the liver as well as microRNA (miR/miRNA) expression changes in the liver and serum of NASH mice model to identify potential biomarker candidates that could predict early fibrosis. This study used 6-week-old C57BL/6NJcl male mice and fed the control with a standard solid diet (CE-2) for breeding and propagation and NASH groups with a high-fat diet [choline-deficient high-fat and 0.1% (w/v) methionine supplemented diet], respectively. Agilent Technologies miRNA microarray was used to investigate microRNA expression in the liver and serum. Hematoxylin and eosin staining of the livers of the NASH group mice during the second week of feeding revealed fatty degeneration, balloon-like degeneration and inflammatory cell infiltration, confirming that the mice were in a state of NASH. The livers of the NASH group mice at 6 weeks of feeding showed fibrosis. Microarray analysis revealed that miRNAs were upregulated and 47 miRNAs were downregulated in the liver of the NASH group. Pathway analysis using OmicsNet predicted miR-29 to target collagen genes. Furthermore, miR-29 was downregulated in the livers of NASH-induced mice but upregulated in serum. These findings suggested that lower miR-29 expression in NASH-induced liver would increase collagen expression and fibrosis. Early liver fibrosis suggests that miR-29 leaks from the liver into the bloodstream, and elevated serum miR-29 levels may be a predictive biomarker for early liver fibrosis.

In their paper, the authors quantified liver iron concentration (LIC) and hepatic steatosis (HS) using MRI-T2* technology in transfusion-dependent thalassaemia (TDT) patients and healthy controls and found that the prevalence of HS among patients with TDT was 36.4%. In comparison with healthy controls, the hepatic fat fraction (FF) was significantly higher in the TDT population (p = 0.013). Active hepatitis C virus infection, body mass index (BMI) and LIC were independent predictors of HS. An inverse correlation between hepatic FF and high-density lipoprotein cholesterol (p = 0.042) and a significant association of high glycaemia level (p = 0.037) with higher hepatic FF and a significant relationship (p = 0.026) between HS and higher BMI (though in a 'lean' group of patients) in TDT patients indicated that 'metabolic syndrome' was present in this subset with TDT. The impact of metabolic syndrome on TDT, including cardiac disease unrelated to iron overload, needs further study. Commentary on: Ricchi et al. Liver steatosis in patients with transfusion-dependent thalassaemia. Br J Haematol 2024;204:2458-2467.

There is a strong association between metabolic dysfunction-associated steatotic liver disease (MASLD) and obesity which are both important risk factors for cardiovascular diseases (CVDs). The current study aimed to assess the association of MBS with different CVDs in patients with MASLD.

The National Inpatient Sample (NIS) database from 2016 to 2020 were analyzed by using ICD-10 codes. A propensity score matching in a 1:1 ratio was done to match the MBS and non-MBS groups.

After weighted analysis, 1,124,155 and 68,215 patients were included in non-MBS and MBS groups, respectively. MBS was associated with significantly lower risk of hospitalization for coronary artery disease (OR 0.633 (0.569-0.703), p value < 0.001), acute myocardial infarction (OR 0.606 (0.523-0.701), p value < 0.001), percutaneous coronary intervention (OR 0.578 (0.489-0.682), p value < 0.001), and thrombolysis (OR 0.765 (0.589-0.993), p value = 0.044) compared to the non-MBS group in patients with MASLD. Furthermore, MBS was associated with 52% reduced risk of hospitalization for hemorrhagic stroke in patients with MASLD (OR 0.481, 95% CI 0.337-0.686, p value < 0.001). However, ischemic stroke was not significant between the two groups (OR 1.108 (0.905-1.356), p value = 0.322). In addition, MBS was associated with 63% and 60% reduced risk of hospitalization for heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) in patients with MASLD (OR 0.373, 95% CI 0.300-0.465 and OR 0.405, 95% CI 0.325-0.504, p value < 0.001 for both), respectively.

The current study showed that MBS is significantly associated with a reduced risk of hospitalization for CVD in patients with MASLD.

Acute liver and kidney injury is the most common complication after aortic surgery, which seriously affects the survival and safety of perioperative patients. The presence of chronic preoperative liver and renal insufficiency, presence of preoperative blood inflammation indicators, duration of intraoperative extracorporeal circulation, and volume of red blood cell transfusion are the main influencing factors for acute postoperative liver and kidney injuries. In recent years, with the research progress on oxidative stress, a growing body of evidence has demonstrated that oxidative stress may cause tissue damage after ischemia-reperfusion (IR). However, the impact of the oxidative stress of distal tissues caused by IR on liver and renal cells after arterial surgeries has not yet been elucidated.

New Zealand white rabbits were used for the experiments and were divided into three groups. Among them, two groups were fed high-fat feed to establish a white rabbit model of hypertriglyceridemia, whereas the control group was provided with ordinary feed. In the experiment, white rabbits were subjected to occlusion of the infrarenal aorta abdominalis to simulate IR of the lower limbs. The effects of high triglyceride levels after the arterial IR of the lower limbs were investigated using the contents of reactive oxygen species (ROS) and malondialdehyde (MDA), a fat metabolite, in ischemic muscle tissues and blood tissues. One of the groups receiving high-fat feed received intervention with reduced glutathione (GSH) before IR of the lower limbs. Pathological studies were performed to identify the expression levels of inflammatory factors and inflammatory cells in liver and renal cells as well as cell apoptosis. The effects of GSH administration before IR on reducing the oxidative stress in adipose tissues and alleviating liver and kidney damage after stress response were investigated.

After IR, the increases in ROS and MDA in ischemic muscle tissues and blood tissues were higher in white rabbits with high triglyceride levels than in those that only received ordinary feed or received intervention with GSH. In addition, for white rabbits with high triglyceride levels, the TNF-α expression levels in the liver increased after IR. Moreover, a considerable increase in the expression of TNF-α, IL-6, macrophages, and T lymphocytes were observed in renal cells. A large number of inflammatory cells and the formation of immune complexes were also noted in the glomeruli; in addition, cell apoptosis was promoted.

This study showed that high triglyceride levels enhanced the oxidative stress response and increased ROS production in New Zealand white rabbits after arterial IR of the lower limbs. High ROS levels activated the expression of inflammatory factors and inflammatory cells in the liver and kidney, which affected cell functions and promoted apoptosis. At high triglyceride levels, GSH downregulated ROS production in oxidative stress after IR, thereby protecting liver and kidney functions.

Overexpression of protein tyrosine phosphatase 1B (PTP1B) disrupts signaling pathways and results in numerous human diseases. In particular, its involvement has been well documented in the pathogenesis of metabolic disorders (diabetes mellitus type I and type II, fatty liver disease, and obesity); neurodegenerative diseases (Alzheimer's disease, Parkinson's disease); major depressive disorder; calcific aortic valve disease; as well as several cancer types. Given this multitude of therapeutic applications, shortly after identification of PTP1B and its role, the pursuit to introduce safe and selective enzyme inhibitors began. Regrettably, efforts undertaken so far have proved unsuccessful, since all proposed PTP1B inhibitors failed, or are yet to complete, clinical trials. Intending to aid introduction of the new generation of PTP1B inhibitors, this work collects and organizes the current state of the art. In particular, this review intends to elucidate intricate relations between numerous diseases associated with the overexpression of PTP1B, as we believe that it is of the utmost significance to establish and follow a brand-new holistic approach in the treatment of interconnected conditions. With this in mind, this comprehensive review aims to validate the PTP1B enzyme as a promising molecular target, and to reinforce future research in this direction.

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.

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.

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.

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.

In assessing individual cardiovascular risk, dyslipidemia is known for emerging as a pivotal factor significantly contributing to major cardiovascular events. However, dyslipidemic patients frequently present with concurrent medical conditions, each with varying frequencies of occurrence; cholangitis, whether acute or chronic, and hepatic steatosis, along with associated conditions, are strongly associated with specific forms of dyslipidemia, and these associations are reasonably well elucidated. Conversely, evidence linking biliary disease to hepatic steatosis is comparatively scant. This narrative review aims to bridge this gap in knowledge concerning the interplay between dyslipidemia, cholangitis, and hepatic steatosis. By addressing this gap, clinicians can better identify patients at heightened risk of future major cardiovascular events, facilitating more targeted interventions and management strategies. The review delves into the intricate relationships between dyslipidemia and these hepatic and biliary clinical conditions, shedding light on potential mechanisms underlying their associations. Understanding these complex interactions is crucial for optimizing cardiovascular risk assessment as well and devising tailored treatment approaches for patients with dyslipidemia and associated hepatic disorders. Moreover, elucidating these connections empowers clinicians with the knowledge needed to navigate the multifaceted landscape of cardiovascular risk assessment and management effectively. By exploring the intricate relationships between dyslipidemia, cholangitis, and hepatic steatosis (without forgetting the possible clinical consequences of hepatic steatosis itself), this review not only contributes to the existing body of knowledge but also offers insights into potential avenues for further research and clinical practice. Thus, it serves as a valuable resource for healthcare professionals striving to enhance patient care and outcomes in the context of cardiovascular disease and associated hepatic conditions.

The relationship between the composite dietary antioxidant index (CDAI), a comprehensive measure of individual dietary antioxidants, and the prevalence and mortality of metabolic syndrome (MetS) remains unknown. We aimed to explore these relationships in the National Health and Nutrition Examination Survey (NHANES). We explored these relationships using two independent cohorts. First, we addressed CDAI and the prevalence of MetS in the general population; second, we explored the association between CDAI and mortality in patients with MetS by following NHANES 2001-2018 participants through December 31, 2019. In addition, restricted cubic spline (RCS), stratified analysis, and sensitivity analysis were used for further interpretation. We included 24,514 participants aged 20-85 years, in which the prevalence of MetS was 27.61 %. CDAI was negatively and dose-responsively associated with the prevalence of MetS, however it was not associated with mortality in patients with MetS. In addition, CDAI was associated with a reduced prevalence of certain components of MetS, including dyslipidemia and central obesity. RCS showed a linear correlation between CDAI and MetS and the above components. Stratified analyses indicated that alcohol consumption was a significant influence of CDAI-MetS and that socioeconomic status and lifestyle specificity existed. Sensitivity analysis confirmed the stability of the results. CDAI was protective against the development of MetS in the general population, but not against mortality in patients with MetS. Clinicians need to develop individualized prevention strategies to reduce the development of MetS by modifying CDAI.

This study compared the prevalences of metabolic syndrome and of cardiac or kidney comorbidities among patients with hepatocellular carcinoma (HCC) associated with metabolic dysfunction-related fatty liver disease (MAFLD), chronic infection with hepatitis B or C virus (HBV or HCV), or the combination of MAFLD and chronic HBV infection.

Medical records were retrospectively analyzed for patients with HCC who underwent hepatectomy between March 2013 and March 2023. Patients with HCC of different etiologies were compared in terms of their clinicodemographic characteristics and laboratory data before surgery.

Of the 2422 patients, 1,822 (75.2%) were chronically infected with HBV without MAFLD and HCV, 415 (17.2%) had concurrent MAFLD and chronic HBV infection but no HCV infection, 121 (5.0%) had MAFLD without hepatitis virus infection, and 64 (2.6%) were chronically infected with HCV in the presence or absence of MAFLD and HBV infection. Compared to patients chronically infected with HBV without MAFLD and HCV, those with MAFLD but no hepatitis virus infection showed significantly lower prevalence of cirrhosis, ascites, portal hypertension, alpha-fetoprotein concentration ≥ 400 ng/mL, tumor size > 5 cm, multinodular tumors and microvascular invasion. Conversely, they showed significantly higher prevalence of metabolic syndrome, hypertension, type 2 diabetes, abdominal obesity, history of cardiovascular disease, T-wave alterations, hypertriglyceridemia and hyperuricemia, as well as higher risk of arteriosclerotic cardiovascular disease. Compared to patients with MAFLD but no hepatitis virus infection, those with concurrent MAFLD and chronic infection with HBV showed significantly higher prevalence of cirrhosis, ascites and portal hypertension, but significantly lower prevalence of hypertension and history of cardiovascular disease. Compared to patients with other etiologies, those chronically infected with HCV in the presence or absence of MAFLD and HBV infection, showed significantly higher prevalence of cirrhosis, portal hypertension, ascites, and esophagogastric varices.

Patients with HCC associated with MAFLD tend to have a background of less severe liver disease than those with HCC of other etiologies, but they may be more likely to suffer metabolic syndrome or comorbidities affecting the heart or kidneys.