Search Results (216)

Obesity, along with dyslipidemia and hyperglycemia, is a metabolic disorder growing in prevalence that is linked to chronic diseases such as atherosclerosis, hypertension, and type 2 diabetes. This study evaluated the anti-obesity, lipid-lowering, and anti-hyperglycemic effects of CB-02 capsules containing dry extracts of Phyllanthus emblica L., Dendrobium catenatum Lindl., and Gynostemma pentaphyllum in HFD-induced obese Swiss albino mice. After 12 weeks of HFD induction, mice were treated orally with CB-02 (576 or 1152 mg/kg/day) for 8 weeks. CB-02 significantly reduced BW gain, AC, the Lee obesity index, and the relative weights of visceral fat and major organs. It also improved lipid profiles by decreasing TC, TG, LDL-C, and non-HDL-C, while increasing HDL-C. These effects were comparable to orlistat (60 mg/kg/day). Furthermore, CB-02 lowered fasting glucose and improved insulin sensitivity, as indicated by an increased QUICKI and HOMA-β and reduced HOMA-IR. Histopathological evaluation showed that CB-02 reduced hepatic steatosis and inflammatory cell infiltration and also attenuated β-cell morphological alterations and pancreatic histopathological damage. These results suggest that CB-02 may be a promising therapeutic candidate for managing obesity and its comorbidities, including dyslipidemia, hyperglycemia, and hepatic steatosis, contributing to the prevention of type 2 diabetes and cardiovascular diseases in obese individuals. Full article

Background: Previous studies have shown a relationship between Visceral Adipose Tissue (VAT) and Hepatic Fat Content (HFC), and increases in HFC are linked to metabolic abnormalities similar to those associated with elevated VAT. Several short-term and long-term studies have supported these findings. Lifestyle interventions remain the cornerstone of treatment for Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), although the ideal dietary regimen is still under debate. Methods: Data on 2040 patients were extracted from the Clinical Nutrition Unit database between 2017 and 2019. Of these, 474 subjects with MASLD and Body Mass Index (BMI) ≥ 35 kg/m² were treated with a four-month low-carbohydrate dietary intervention called the “Strong Diet” (StD). VAT and liver stiffness were measured at baseline and after four months of treatment using ultrasound. Results: Our study demonstrates the significant efficacy of StD in reducing VAT in MASLD patients with moderate hepatic steatosis. In subjects with severe steatosis, there is no statistically significant response to dietary intervention. This may be attributed to several irreversible molecular mechanisms that fundamentally alter the hepatic microenvironment and limit the liver’s capacity for regeneration and metabolic recovery. Conclusions: Improvements were largely confined to patients with moderate MASLD, with limited benefit in severe disease. Although dietary intervention remains the cornerstone of MASLD management, patients with severe steatosis should be informed about the potential limited resolution of steatosis, even with optimal metabolic control. Full article

Objective: The study investigates the dietary effects of Moringa oleifera leaf powder on obesity, blood biochemical parameters, and organ health in hyperlipidemic zebrafish (Danio rerio). Methodology: Adult hyperlipidemic zebrafish (n = 56/group) were fed for 12 weeks either with a high-cholesterol diet (HCD, 4% w/w) or HCD supplemented with 0.5% (w/w) M. oleifera leaf powder (0.5% MO) or HCD with 1.0% (w/w) M. oleifera leaf powder (1.0% MO). At different time points (0 to 12 weeks), the survivability and body weight (BW) of zebrafish were measured, while various biochemical and histological evaluations were performed after 12 weeks of feeding the respective diets. Additionally, an in silico approach was used to assess the binding interactions of MO phytoconstituents with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Results: Following 12-week supplementation, higher zebrafish survivability was observed in the MO-supplemented groups compared to the survivability of the HCD group. Relative to the initial BW, only 4% BW enhancement was observed post 12 weeks of dietary intake of 1.0% MO, in contrast to 27% BW gain in the HCD group. MO supplementation at both (0.5% and 1.0%) effectively mitigates the HCD-induced dyslipidemia and significantly minimizes the atherogenic coefficient and atherogenic index. Similarly, MO reduces elevated blood glucose levels, the ALT/AST ratio, and augments ferric ion reduction (FRA) and paraoxonase (PON) activity in a dose-dependent manner. Likewise, MO (particularly at 1.0%) effectively restrained HCD-induced steatosis, hepatic interleukin (IL)-6 production, and protected the kidneys, testes, and ovaries from oxidative stress and cellular senescence. The in silico findings underscore that the six phytoconstituents (chlorogenic acid, isoquercetin, kaempferol 3-O-rutinoside, astragalin, apigetrin, and myricetin) of MO exhibited a strong interaction with HMG-CoA reductase active and binding site residues via hydrogen and hydrophobic interactions. Conclusions: The findings demonstrated an antioxidant, anti-inflammatory, and hypoglycemic effect of MO, guiding the events to prevent HCD-induced metabolic stress and safeguard vital organs. Full article

Lean metabolic dysfunction-associated steatotic liver disease (lean MASLD) challenges longstanding views that link hepatic steatosis primarily to obesity. Emerging as a distinct and under-recognized clinical entity, lean MASLD affects individuals with a normal body mass index (BMI), yet carries risks of cardiovascular disease, hepatocellular carcinoma, and liver-related mortality comparable to obesity-associated MASLD. The absence of overt metabolic dysfunction complicates diagnosis, revealing critical limitations in current screening frameworks centered on BMI. This review synthesizes evolving clinical insights and epidemiological trends in lean MASLD, and delineates its unique pathophysiological mechanisms. Recent advances in metabolomics have uncovered disease-specific disruptions in lipid and amino acid metabolism, bile acid signaling, and gut microbiota-derived metabolites. By integrating evidence from metabolic, genetic, and epigenetic domains, we identified promising biomarkers, and therapeutic targets that may support earlier detection and precision-guided treatment strategies. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing public health concern influenced by both genetic and metabolic factors. Polygenic risk scores (PRSs), which combine the effects of known single-nucleotide polymorphisms (SNPs), may improve early risk stratification. We conducted an observational study on 298 MASLD patients: 148 from a Hepatology Unit and 150 from a Bariatric Surgery Unit. Genotyping was performed for the PNPLA3, TM6SF2, MBOAT7, and GCKR variants. A PRS was calculated and used to stratify patients by genetic risk. Liver fibrosis was assessed using the FIB-4 index, and a subset also underwent transient elastography. Clinical, biochemical, and anthropometric data were analyzed across genetic strata. PRSs showed positive correlations with AST, ALT, and FIB-4, indicating increased liver injury and fibrosis risk with higher genetic burden. Transaminases increased significantly across PRS quartiles (p < 0.05), and individuals with PRS > 0.532 exhibited elevated AST, ALT, and borderline FIB-4. Variant-specific associations included PNPLA3 with increased AST and MBOAT7 with higher hepatic steatosis (CAP). Subgroup analyses revealed distinct genetic and phenotypic patterns between the two clinical cohorts. These findings support the additive role of genetic risk in MASLD progression and underscore the value of polygenic profiling for the early identification and personalized management of high-risk patients. Full article

Obstructive sleep apnea (OSA), characterized by intermittent hypoxia (IH), is strongly associated with metabolic syndrome and metabolic dysfunction-associated steatotic liver disease (MASLD). IH exacerbates MASLD progression through oxidative stress, inflammation, and lipid accumulation. This study aims to investigate the impact of oxygen normalization on metabolic dysfunction in OSA patients using continuous positive airway pressure (CPAP) therapy, and in mice exposed to IH followed by a reoxygenation period. In the clinical study, 76 participants (44 OSA patients and 32 controls) were analyzed. OSA patients had higher insulin resistance, triglycerides, very low density lipoprotein (VLDL) content, and liver enzyme levels, along with a higher prevalence of liver steatosis. After 18 months of CPAP therapy, OSA patients showed significant improvements in insulin resistance, lipid profiles (total cholesterol and VLDL), liver function markers (AST and albumin), and steatosis risk scores (Fatty Liver Index and OWLiver test). In the experimental study, IH induced hepatic lipid accumulation, oxidative stress, and inflammation, and reoxygenation reversed these deleterious effects in mice. At the molecular level, IH downregulated fatty acid oxidation (FAO)-related genes, thus impairing the FAO process. Reoxygenation maintained elevated levels of lipogenic genes but restored FAO gene expression and activity, suggesting enhanced lipid clearance despite ongoing lipogenesis. Indeed, serum β hydroxybutyrate, a key marker of hepatic FAO in patients, was impaired in OSA patients but normalized after CPAP therapy, supporting improved FAO function. CPAP therapy improves lipid profiles, liver function, and MASLD progression in OSA patients. Experimental findings highlight the therapeutic potential of oxygen normalization in reversing IH-induced liver damage by FAO pathway restoration, indicating a metabolic reprogramming in the liver. Full article

Background/Objectives: We aimed to identify questionnaire items associated with an increased risk of developing hepatic steatosis in the general population. Methods: A total of 15,063 individuals aged ≥20 years who underwent general health checkups and had no hepatic steatosis at baseline were included. The relationship between questionnaire data at baseline and hepatic steatosis incidence over a median 4.2-year follow-up was investigated across body mass index (BMI) categories. Results: Among 15,063 individuals (mean [SD] age, 47.1 [10.2] years; 6769 [44.9%] male; mean [SD] BMI, 21.4 [2.6] kg/m²), 1889 individuals (12.5%) developed hepatic steatosis during follow-up. After adjusting for age, sex, and factors related to metabolic diseases and liver injury, the strongest questionnaire-based risk factor for hepatic steatosis was self-reported weight gain of 10 kg or more after the age of 20 across all BMI categories: total population (hazard ratio [HR], 2.11; 95% confidence interval [CI], 1.90–2.34; p < 0.001), Category 1 (BMI < 22) (HR, 2.33; 95% CI, 1.86–2.91; p < 0.001), Category 2 (BMI 22 to <25) (HR, 1.43; 95% CI, 1.25–1.63; p < 0.001), and Category 3 (BMI ≥ 25) (HR, 1.41; 95% CI, 1.12–1.77; p = 0.003). Conclusions: In this cohort study, self-reported weight gain of 10 kg or more after the age of 20 was associated with an increased risk of hepatic steatosis, independent of baseline BMI. Questionnaires capturing weight gain history may support universal screening efforts to identify individuals at elevated risk. Full article

Cholesterol accumulation plays a significant role in the pathogenesis of metabolic-dysfunction-associated steatotic liver disease (MASLD), yet changes in cholesterol homeostasis in MASLD remain insufficiently investigated. This study aimed to examine alterations in cholesterol synthesis and absorption by measuring plasma levels of endogenous cholesterol precursors (as markers of synthesis) and phytosterols (as indicators of absorption). A total of 124 MASLD patients and 43 healthy individuals were included. Our results showed higher plasma concentrations of lathosterol in the MASLD group (p = 0.006), in parallel with comparable concentrations of desmosterol (p = 0.472) and all analyzed phytosterols in both groups. Correlation analysis showed that both lathosterol and desmosterol were positively associated with non-invasive hepatic steatosis indices: FLI, HSI, and TyG index (p < 0.01, p < 0.01, and p < 0.05, respectively). Multivariate linear regression further confirmed that these synthesis markers remained significant predictors of FLI (p = 0.010), HSI (p = 0.013), and TyG index (p = 0.002), even after adjusting for other relevant variables. These findings indicate that MASLD is associated with a shift in cholesterol homeostasis towards enhanced endogenous cholesterol synthesis. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver condition globally, strongly linked to obesity, insulin resistance, and type 2 diabetes (T2D). Tirzepatide (TZP), a dual GIP/GLP-1 receptor agonist, improves glycemic control and reduces body weight and the liver fat content in patients with obesity and T2D. However, its effect on liver-specific outcomes such as steatosis and fibrosis remains incompletely characterized. Low-energy ketogenic therapy (LEKT), a nutritional strategy characterized by carbohydrate restriction and nutritional ketosis, may enhance hepatic β-oxidation and reduce hepatic lipogenesis. To date, however, the combination of TZP and LEKT has not been studied in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to compare the hepatic and metabolic effects of TZP combined with either LEKT or a conventional low-calorie diet (LCD) over a 12-week period. Methods: Sixty adult patients with MASLD undergoing TZP therapy were prospectively assigned to either an LEKT or a conventional LCD, with 30 participants per group. As primary endpoints, the controlled attenuation parameter (CAP, an index of hepatic steatosis) and liver stiffness measurement (LSM, an index of liver fibrosis) were assessed at the baseline and after 12 weeks using FibroScan^®. Secondary outcomes included changes in body mass index (BMI), glycated hemoglobin (HbA1c), and liver enzymes. Adherence to both diet and pharmacological treatment, as well as tolerability, were systematically monitored throughout the intervention period. Results: Both groups showed significant reductions in body weight (TZP + LEKT, p = 0.0289; TZP + LCD, p = 0.0278), with no significant intergroup difference (p = 0.665). CAP and LSM improved significantly in both groups, but reductions were greater in the TZP + LEKT group (CAP −12.5%, p < 0.001; LSM −22.7%, p < 0.001) versus LCD (CAP −6.7%, p = 0.014; LSM −9.2%, p = 0.022). Between-group differences were statistically significant for both CAP (p = 0.01) and LSM (p = 0.03). Conclusions: Based on these preliminary findings, we support the hypothesis that the combination of TZP and LEKT may be superior to TZP with an LCD in reducing hepatic steatosis and stiffness in individuals with obesity. Full article

Background/Objectives: We evaluated the efficacy of a good lifestyle intervention on the severity of metabolic dysfunction-associated steatotic liver disease (MASLD) in children with Down syndrome (DS). Methods: This retrospective longitudinal study included 31 children with Down syndrome (DS) who were affected by MASLD and attended nutritional counseling based on a nutritional approach (e.g., Mediterranean diet and antioxidant supplements), as well as physical exercise. Clinical parameters, markers of low-grade systemic inflammation, and hepatic steatosis, as assessed by ultrasound, were evaluated at baseline (T0) and after 6 months (T1). Results: Several anthropometric and biochemical parameters, including body mass index, waist circumference, diastolic and systolic blood pressure, aspartate aminotransferase, basal insulin, insulin resistance, pro-inflammatory interleukin-1β, and anti-inflammatory interleukin-10, showed significant improvement after 6 months of a nutritional approach. This study also found a regression of at least one grade of hepatic steatosis in a significant portion of patients, especially in those who received antioxidant supplements. Conclusions: Our study further supports the hypothesis that a healthy lifestyle intervention, based on adherence to the Mediterranean diet, natural supplements with antioxidant properties, and regular physical activity, can be considered a safe therapeutic approach for reducing the risk and severity of MASLD in children with DS. Full article

Background/Objectives: This study aimed to evaluate adipose tissue dysfunction, assessed through adipocytokines and proinflammatory cytokines, in relation to hepatic steatosis (HS) in patients with newly diagnosed type 2 diabetes (T2D). Methods: An observational study evaluated 155 consecutive patients with new-onset T2D; 118 (76.1%) were found to have HS, while the remaining 37 served as the control group without steatosis. Anthropometric status and body mass index (BMI) were evaluated. The biochemical assessment encompassed the measurements of fasting serum lipids, fasting plasma glucose (FPG), liver function tests, adiponectin, leptin, resistin, tumor necrosis factor (TNF-α), and interleukin 6 (IL-6). Insulin resistance (IR) was determined using the homeostasis model assessment (HOMA). HS was evaluated using ultrasonographic criteria. Quantitative evaluation of HS was performed by calculating the hepatic steatosis index (HSI). Results: There were statistically significant differences between the groups for age, BMI, weight, waist circumference (WC) and hip circumference, HSI, glucose profile (fasting plasma glucose (FPG), HOMA-IR), liver function tests, adiponectin, leptin, resistin, TNF-α, and IL-6. In multivariate logistic regression analysis, age, smoking, BMI, WC, HOMA-IR, and hypoadiponectinemia were the only independent factors associated with HS. Conclusions: The adipose tissue dysfunction assessed through adipocytokines and proinflammatory cytokines is part of the associated disorders in HS and new-onset T2D. In patients with newly diagnosed T2D, age, smoking, and hypoadiponectinemia consistently emerged as independent predictors of hepatic steatosis. More prospective trials are needed to clarify the “the temporal onset” of adipose tissue dysfunction. Full article

Ultrasound attenuation imaging (ATI) is a non-invasive method for quantifying hepatic steatosis, offering advantages over the hepatorenal index (HRI). However, its reliability can be influenced by factors such as measurement depth, ROI size, and subcutaneous fat. This paper examines the impact of these confounders on ATI measurements and discusses diagnostic considerations. In this study, 33 healthy adults underwent liver ultrasound with ATI and HRI protocols. ATI measurements were taken at depths of 2–5 cm below the liver capsule using small and large ROIs. Two operators performed the measurements, and inter-operator variability was assessed. Subcutaneous fat thickness was measured to evaluate its influence on attenuation values. The ATI measurements showed a consistent decrease in attenuation coefficient values with increasing depth, approximately 0.05 dB/cm/MHz. Larger ROI sizes increased measurement variability due to greater anatomical heterogeneity. HRI values correlated weakly with ATI and were influenced by operator technique and subcutaneous fat, the latter accounting for roughly 2.5% of variability. ATI provides a quantitative assessment of hepatic steatosis compared to HRI, although its accuracy can vary depending on the depth and ROI selection. Standardised imaging protocols and AI tools may improve reproducibility and clinical utility, supporting advancements in ultrasound-based liver diagnostics for better patient care. Full article

Background/Objectives: Acromegaly is associated with multiple metabolic comorbidities, but the relationship between disease activity and metabolic dysfunction-associated steatotic liver disease (MASLD) or cardiovascular risk remains unclear. This study aimed to assess the prevalence and severity of MASLD and liver fibrosis in patients with acromegaly relative to healthy controls and explore whether disease activity influences these parameters. We also evaluated cardiovascular risk indicators in acromegaly patients. Methods: A retrospective case-control study was conducted between 2000 and 2022, involving 58 acromegaly patients and 58 healthy controls. Patients were classified as active or in biochemical remission. MASLD was assessed using the fibrosis-4 (FIB-4) index, MASLD fibrosis score, body mass index, diabetes (BARD) score, the aspartate aminotransferase-to-platelet index (APRI), and the aspartate aminotransferase-to-alanine aminotransferase ratio. Cardiovascular evaluation included pulse wave velocity (PWV) and carotid intima–media thickness (CIMT). Results: The median age of the acromegaly group was 47.5 (39–57) years, compared to 42 (40–48) years in the control group (p = 0.041). APRI (p < 0.001), FIB-4 (p < 0.001), MASLD fibrosis score (p < 0.001), and BARD score (p < 0.001) were significantly higher in the acromegaly group. The prevalence of hepatic steatosis was also higher in the acromegaly group (p < 0.001). Diastolic blood pressure (p = 0.015) and PWV (p = 0.012) were significantly higher in the acromegaly group. Conclusions: Acromegaly patients have an increased risk of MASLD and fibrosis, but this risk is unassociated with disease activity. Similarly, cardiovascular risk parameters remain elevated regardless of disease activity. These findings suggest that the systemic effects of acromegaly may persist despite biochemical control. Full article

Background: Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular disorder caused by mutations in the DMD gene, leading to progressive muscle degeneration, loss of ambulation, and multi-systemic complications. Beyond its impact on mobility, DMD is associated with significant endocrine and metabolic dysfunctions that develop over time. Objective: To provide a comprehensive analysis of growth disturbances, endocrine dysfunctions, and metabolic complications in DMD including bone metabolism, considering the underlying mechanisms, clinical implications, and management strategies for daily clinical guidance. Methods: In this narrative review, an evaluation of the literature was conducted by searching the Medline database via the PubMed, Scopus, and Web of Science interfaces. Results: Growth retardation is a hallmark feature of DMD, with patients exhibiting significantly shorter stature compared to their healthy peers. This is exacerbated by long-term glucocorticoid therapy, which disrupts the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis and delays puberty. Obesity prevalence follows a biphasic trend, with increased risk in early disease stages due to reduced mobility and corticosteroid use, followed by a decline in body mass index (BMI) in later stages due to muscle wasting. Metabolic complications, including insulin resistance, altered lipid metabolism, and hepatic steatosis, further characterize disease burden. Osteoporosis and increased fracture risk, primarily due to reduced mechanical loading and glucocorticoid-induced bone resorption, are major concerns, needing early screening and intervention. The RANK/RANKL/OPG signaling pathway has emerged as a critical factor in bone deterioration, providing potential therapeutic targets for improving skeletal health. Conclusions: Growth and endocrine disorders in DMD are complex and multifactorial, requiring proactive monitoring and early intervention. Addressing these issues requires a multidisciplinary approach integrating endocrine, nutritional, and bone health management. Further research is essential to refine treatment strategies that mitigate growth and metabolic disturbances while preserving overall patient well-being. Full article

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is a leading cause of liver cirrhosis, with its global prevalence rising due to obesity, insulin resistance, and type 2 diabetes mellitus. While bariatric surgery remains effective for weight loss, Glucagon-Like Peptide-1 analogs such as liraglutide are emerging as promising pharmacological treatments. This study aimed to evaluate the effects of a 3-month liraglutide treatment on liver steatosis, subclinical markers, and insulin resistance in non-diabetic, obese patients with MASLD. Twenty-eight obese adults (BMI ≥ 30 kg/m²) were treated with daily subcutaneous liraglutide injections for three months. Liver steatosis was assessed using FibroScan^® (CAP score) and non-invasive indices (Hepatic Steatosis Index—HSI, and NAFLD Liver Fat Score—NLFS). Insulin resistance was measured with conventional markers (HOMA-IR, QUICKI) and triglyceride-based indices (METS-IR, TyG). Liraglutide significantly reduced liver steatosis (CAP score: 305 to 268 dB/m, p < 0.05) and improved HSI, while NLFS remained unchanged. Despite significant weight loss, traditional insulin resistance markers remained unchanged, while METS-IR and TyG improved. Liraglutide therapy improved liver steatosis and triglyceride-based insulin resistance markers in non-diabetic obese patients with MASLD. These findings support the use of liraglutide, highlighting the value of personalized approaches and alternative insulin resistance assessments in MASLD management. Full article