Metabolic-Dysfunction-Associated Steatotic Liver Disease: Molecular Mechanisms, Clinical Implications, and Emerging Therapeutic Strategies

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 2959 - 2959

Published: March 25, 2025

Metabolic-dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty (NAFLD), is a highly prevalent metabolic disorder characterized by hepatic steatosis in conjunction with at least one cardiometabolic risk factor, such obesity, type 2 diabetes, hypertension, or dyslipidemia. As global rates of obesity and syndrome continue to rise, MASLD becoming major public health concern, projections indicating substantial increase prevalence over the coming decades. The spectrum ranges from simple metabolic-dysfunction-associated steatohepatitis (MASH), fibrosis, cirrhosis, hepatocellular carcinoma, contributing significant morbidity mortality worldwide. This review delves into molecular mechanisms driving pathogenesis, including dysregulation lipid metabolism, chronic inflammation, oxidative stress, mitochondrial dysfunction, gut microbiota alterations. Recent advances research have highlighted role genetic epigenetic factors progression, well novel therapeutic targets peroxisome proliferator-activated receptors (PPARs), fibroblast growth factors, thyroid hormone receptor beta agonists. Given multifaceted nature MASLD, multidisciplinary approach integrating early diagnosis, insights, lifestyle interventions, personalized therapies critical. underscores urgent need for continued innovative treatment strategies precision medicine approaches halt progression improve patient outcomes.

Language: Английский

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Association between the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio and metabolic dysfunction-associated steatotic liver disease

Frontiers in Nutrition, Journal Year: 2025, Volume and Issue: 12

Published: March 3, 2025

Background Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the most widespread chronic diseases and a serious global public health problem. Further research to identify novel risk factors associated with MASLD urgently needed. The non-high-density lipoprotein cholesterol high-density ratio (NHHR) was identified as lipid marker. objective this assess association between NHHR in adults. Methods This cross-sectional study utilized data from 2017–2020 National Health Nutrition Examination Survey (NHANES). diagnosed accordance controlled attenuation parameter scores combination cardiometabolic factors. Multivariate logistic regression analyses, conjunction restricted cubic spline method, were employed investigate risk. Furthermore, subgroup interaction analyses conducted. Results included 5,269 individuals, 2,031 individuals 3,238 without MASLD. Logistic revealed significant positive correlation After confounding adjusted, each unit rise correlated 39% higher probability (OR = 1.39, 95% CI: 1.13–1.69). Subgroup that held steady regardless age, gender, race, poverty-to-income ratio, education level, physical activity, body mass index, diabetes, hypertension, dyslipidemia smoking status ( P for >0.05). In addition, non-linear relationship an S-shaped manner found, inflection point at 1.59. Conclusion Our findings imply increasing trend greater development. has potential function indicator estimating likelihood developing

Language: Английский

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Untargeted lipidomic analysis of metabolic dysfunction-associated steatohepatitis in women with morbid obesity

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(3), P. e0318557 - e0318557

Published: March 4, 2025

Metabolic Dysfunction-Associated Steatohepatitis (MASH) represents the severe condition of Steatotic Liver Disease (MASLD). Currently, there is a need to identify non-invasive biomarkers for an accurate diagnosis MASH. Previously, omics studies identified alterations in lipid metabolites involved MASLD. However, these require validation other cohorts. In this sense, our aim was perform lipidomics circulating metabolite profile We assessed liquid chromatography coupled mass spectrometer-based untargeted lipidomic assay serum samples 216 women with morbid obesity that were stratified according their hepatic into Normal (NL, n = 44), Simple Steatosis (SS, 66) and MASH (n 106). First, we are increased MASLD, composed ceramides, triacylglycerols (TAG) some phospholipids. Then, patients SS have characteristic levels diacylglycerols DG (36:2) (36:4), TAG few phospholipids such as PC (32:1), PE (38:3), (40:6), PI (32:0) (32:1). Later, patients, found deoxycholic acid, set TAG, PC, PE, LPI; while decreased (36:0). Finally, reported panel might be used differentiate from made up 9-HODE LPI (16:0) To conclude, investigation has suggested associated MASLD Specifically, seems discriminatory subjects compared individuals. Thus, could diagnostic tool.

Language: Английский

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Metabolic effects and mechanism of action of the pan PPAR agonist Lanifibranor

Journal of Hepatology, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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Significance of FXR agonists in MASLD treatment: a deep dive into lipid alteration by analytical techniques

Published: March 25, 2025

Metabolic dysfunction-associated steatotic liver disease (MASLD) is rapidly emerging as a global health crisis, affecting over 30% of the population and demanding urgent attention. This redefined condition, previously known non-alcoholic fatty (NAFLD), reflects deeper understanding intricate interplay between metabolic dysfunction health. At heart MASLD lies troubling accumulation triglycerides (TGs) in hepatocytes, which precipitates insulin resistance oxidative stress, ultimately leading to more severe forms like steatohepatitis (MASH). Excitingly, recent research has spotlighted farnesoid X receptor (FXR) groundbreaking therapeutic target. FXR not only regulates lipid metabolism but also combats inflammation resistance, making it potential game-changer fight against MASLD. With one FDA-approved drug, resmetirom, currently available, exploration agonists opens new avenues for innovative treatments that could revolutionize patient care. By harnessing power restore balance integrating advanced strategies lipidomics acid profiling, we stand on brink transforming how approach its associated complications, paving way healthier future. review delves into promising role combating implications related disorders, emphasizing urgency detect manage this burgeoning epidemic.

Language: Английский

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Uncovering hepatic transcriptomic and circulating proteomic signatures in MASH: A meta-analysis and machine learning-based biomarker discovery

Computers in Biology and Medicine, Journal Year: 2025, Volume and Issue: 191, P. 110170 - 110170

Published: April 12, 2025

Language: Английский

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Understanding the Link Between Sterol Regulatory Element Binding Protein (SREBPs) and Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD)

Current Obesity Reports, Journal Year: 2025, Volume and Issue: 14(1)

Published: April 14, 2025

Language: Английский

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Antioxidant and In Vitro Hepatoprotective Activities of a Polyphenol-Rich Fraction from the Peel of Citrus lumia Risso (Rutaceae)

Plants, Journal Year: 2025, Volume and Issue: 14(8), P. 1209 - 1209

Published: April 15, 2025

Citrus lumia Risso is an ancient, cultivated Mediterranean lime belonging to the Rutaceae family. It a species extremely difficult retrieve, but it still found in some private gardens certain regions of Southern Italy. fruits are rich source bioactive compounds, particularly polyphenols, which have been linked reduction risk several metabolic diseases. Here, hesperidium peel extracts were obtained by maceration with ethanol:water mixtures different proportions (50:50, 80:20, 0:100) and resulting crude then passed through glass column containing adsorbent resins concentrate polyphenolic compounds. After phytochemical characterization, evaluated for antioxidant activity using electron paramagnetic resonance (EPR) spectroscopy. Finally, water polyphenolic-rich extract (ClumWp), was highest flavonoid content (18.355 ± 1.607 mg/mL) strongest against hydroxyl radical, tested evaluate its potential protective effects on lipid accumulation both 2D hepatocyte cultures 3D spheroids. Treatment 25 50 μg/mL resulted intracellular HepG2 liver cell line, while treatment 100 µg/mL ClumWp + LX2 In addition, significantly increased ATP levels spheroids compared those untreated, suggesting ability restore promote production. Our results highlight that study neglected species, such as Risso, remains valuable opportunity valorize biodiversity, especially context applications improve human health. particular, fraction showed promising metabolism cellular energy balance may prove disorders MASLD, where disrupts normal functions.

Language: Английский

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Targeting Metabolism: Innovative Therapies for MASLD Unveiled

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(9), P. 4077 - 4077

Published: April 25, 2025

The recent introduction of the term metabolic-dysfunction-associated steatotic liver disease (MASLD) has highlighted critical role metabolism in disease’s pathophysiology. This innovative nomenclature signifies a shift from previous designation non-alcoholic fatty (NAFLD), emphasizing condition’s progressive nature. Simultaneously, MASLD become one most prevalent diseases worldwide, highlighting urgent need for research to elucidate its etiology and develop effective treatment strategies. review examines delineates revised definition MASLD, exploring epidemiology pathological changes occurring at various stages disease. Additionally, it identifies metabolically relevant targets within provides summary latest targeted drugs under development, including those clinical some preclinical stages. finishes with look ahead future therapy goal summarizing providing fresh ideas insights.

Language: Английский

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Empagliflozin Alleviates Hepatic Steatosis and Oxidative Stress via the NRF1 Pathway in High-Fat Diet-Induced Mouse Model of Metabolic Dysfunction-Associated Steatotic Liver Disease

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(9), P. 4054 - 4054

Published: April 25, 2025

Empagliflozin (EMPA)—a sodium-glucose cotransporter type 2 inhibitor—reduces endoplasmic reticulum (ER) stress, oxidative and inflammation during metabolic dysfunction-associated steatotic liver disease (MASLD) progression. However, the direct effects of EMPA on hepatic lipid metabolism stress are unclear. Through current study, we seek to explore related mechanisms in MASLD. To this end, MASLD was induced C57BL/6J mice using a high-fat diet (HFD); nuclear respiratory factor 1 (NRF1) downregulated via viral transduction (AAV8-shNrf1). Glucose homeostasis histology were assessed, measured. HFD-fed mice-derived tissue samples exhibited more droplets, higher triglyceride levels, elevated ER than chow (CD)-fed mice. attenuated HFD-induced stress. Additionally, HFD significantly decreased NRF1 Sirtuin (SIRT)7 expression compared with CD, which rescued by treatment. these results did not affect insulin resistance or synthesis-related changes upon treatment Nrf1-knockdown Furthermore, alleviated steatosis stress; however, lost Collectively, study suggest that ameliorates reducing attenuating NRF1.

Language: Английский

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