Research progress on AMPK in the pathogenesis and treatment of MASLD

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Март 11, 2025

Metabolic dysfunction-associated steatotic liver disease (MASLD; formerly known as non-alcoholic fatty disease, NAFLD) has become one of the most prevalent chronic diseases worldwide, with its incidence continuously rising alongside epidemic metabolic disorders. AMP-activated protein kinase (AMPK), a key regulator cellular energy metabolism, influences multiple pathological processes associated MASLD. This review systematically summarizes regulatory roles AMPK in lipid inflammatory response, cell apoptosis, and fibrosis. Additionally, it discusses latest developments activators from preclinical to clinical studies, while analyzing major challenges currently faced potential strategies for resolution. A deeper understanding mechanisms will contribute development more effective therapeutic approaches

Язык: Английский

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

Опубликована: Март 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.

Язык: Английский

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Advancing Cardiovascular, Kidney, and Metabolic Medicine: A Narrative Review of Insights and Innovations for the Future

Diabetes Therapy, Год журнала: 2025, Номер unknown

Опубликована: Апрель 24, 2025

Cardiovascular, kidney and metabolic (CKM) conditions are interrelated, significantly contributing to morbidity, mortality healthcare burden. Despite therapeutic advances, traditional disease-specific approaches often fail address their complex interplay. Key agents-including glucagon-like peptide-1 receptor agonists (GLP-1 RAs), dual GLP-1/glucose-dependent insulinotropic polypeptide RAs, sodium glucose co-transporter inhibitors the nonsteroidal mineralocorticoid antagonist (MRA) finerenone-offer multi-organ benefits. Emerging therapies, such as triple second-generation MRAs, target new pathways further expanding treatment options for CKM conditions. A holistic management approach must recognise that dysfunction-associated steatotic liver disease, steatohepatitis, obstructive sleep apnoea obesity part of spectrum. Frailty assessment is also important alongside conditions, warranting comprehensive geriatric deprescribing when appropriate. Multidisciplinary care-including lifestyle interventions, pathway redesign, pharmacological advances novel technologies-is essential improving outcomes. As landscape evolves, future strategies should prioritise early intervention, personalised addressing unmet needs in high-risk populations. This review advocates an integrated framework, exploring strategies, emerging therapies technological innovations. It examines role artificial intelligence digital health tools risk stratification, diagnosis long-term condition management, ethical regulatory considerations.

Язык: Английский

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Use of Metabolic Scores and Lipid Ratios to Predict Metabolic Dysfunction-Associated Steatotic Liver Disease Onset in Patients with Inflammatory Bowel Diseases

Journal of Clinical Medicine, Год журнала: 2025, Номер 14(9), С. 2973 - 2973

Опубликована: Апрель 25, 2025

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized in inflammatory bowel (IBD) patients due to chronic inflammation and metabolic disturbances. However, reliable non-invasive biomarkers for MASLD prediction this population are lacking. This study evaluated the predictive value of scores lipid ratios onset IBD patients. Methods: An observational retrospective was conducted on 358 at “Renato Dulbecco” Teaching Hospital Catanzaro, Italy, a period between 1 January 2021 31 December 2024. Clinical laboratory data, including ratios, were analyzed using chi-square Kruskal–Wallis tests as appropriate. Post hoc comparisons Dunn’s test. Receiver operating characteristic analysis assessed their accuracy MASLD. p < 0.05 considered significant. Results: IBD-MASLD had significantly higher body mass index (BMI, 27 ± 4 vs. 22 2 kg/m2; 0.001), waist circumference (100 11 85 cm; other anthropometric parameters, scores, than IBD-only The score insulin resistance [METS-IR, area under curve (AUC = 0.754)] 0.754) exhibited highest accuracy, followed by accumulation product (LAP, AUC 0.737), BMI 0.709), triglyceride/high-density lipoprotein (TG/HDL, 0.701). Insulin homeostasis model assessment 0.680) triglyceride-glucose 0.674), moderate use. visceral adiposity 0.664) low-density lipoprotein/high-density 0.656) showed lower discriminative ability, while fibrosis-4 0.562) weakest diagnostic performance. Conclusions: Our findings suggest that primarily driven cardiometabolic dysfunction. introduction METS-IR, LAP, TG/HDL into clinical assessments could prove useful preventing cardiovascular complications setting.

Язык: Английский

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Cardiac and liver impairment on multiorgan MRI and risk of major adverse cardiovascular and liver events

Nature Medicine, Год журнала: 2025, Номер unknown

Опубликована: Май 7, 2025

Abstract Cardiovascular disease and metabolic dysfunction-associated steatotic liver are common conditions associated with high mortality morbidity, yet opportunities for integrated prevention underinvestigated. We explored the association between impairment in (defined by increased iron-corrected T1 (cT1) time) and/or heart (reduced left ventricular ejection fraction ≤ 50) risk of experiencing cardiovascular- or liver-related events all-cause among 28,841 UK Biobank participants who underwent magnetic resonance imaging. Using Cox proportional hazard models, adjusted age, sex, body mass index, type 2 diabetes dyslipidaemia, we observed that cardiac was incidence cardiovascular (hazard ratio (HR) 2.3 (1.9–2.7)) hospitalization (HR 2.1 (1.8–2.4)). Liver incident (cT1 ≥ 800 ms, HR 1.3 (1.1–1.5)), 875 9.2 (3.2–26) 5.5 (3.2–9.3). Associations cT1 were maintained ( N = 6,223). Reduced (≤50) combined elevated (≥800 ms) earlier (time to event 0.8 versus 2.4 years; P < 0.05). Cardiac independently, combination, events, suggesting a dual role imaging pathways.

Язык: Английский

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Two-Year Mediterranean Diet Intervention Improves Hepatic Health in MASLD Patients

Foods, Год журнала: 2025, Номер 14(10), С. 1736 - 1736

Опубликована: Май 14, 2025

Background: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is one of the leading causes chronic liver disease, affecting 30% global adult population and continuing to rise. Objective: We aimed assess effect a two-year follow-up Mediterranean diet intervention on parameters health in MASLD patients. Methods: Sixty-two people between 40 60 years age, all diagnosed with MASLD, were enrolled clinical trial, who randomly assigned three interventions following pattern promotion physical activity. After intervention, participants categorized into two groups according their progress adhering (MedDiet), which was assessed at four time points, conducted start this study after 6, 12, 24 months intervention. A multivariate general linear model adjusted for sex, (diet activity) used. Bonferroni's post hoc test identified differences sessions within same group. Results: Participants highly adherent group showed significantly stronger improvement anthropometric measures, lipid profile, enzyme levels during period, along reduction Dietary Inflammatory Index, intrahepatic fat content, fatty index, plasma cytokeratin-18 compared baseline. The observed several 12 came standstill, likely because COVID-19 pandemic that time. At months, pandemic, these improved as result better adherence diet. Conclusions: Greater diet, increased activity, enhances markers individuals MASLD. These findings support lifestyle an effective non-pharmacological strategy improve prevent liver-related complications patients, potentially reducing future public burden.

Язык: Английский

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From liver to limb: Exploring the association between fatty liver disease and peripheral artery disease—A systematic review

European Journal of Clinical Investigation, Год журнала: 2025, Номер unknown

Опубликована: Май 19, 2025

Abstract Introduction Fatty liver disease, encompassing nonalcoholic fatty disease (NAFLD), metabolic dysfunction‐associated (MAFLD), and the recently redefined steatotic (MASLD), is a growing global health concern with significant cardiovascular implications. Peripheral artery (PAD), common manifestation of systemic atherosclerosis, shares key pathophysiological mechanisms including insulin resistance, inflammation endothelial dysfunction. Although emerging evidence suggests link between PAD, nature extent this association remain unclear. This systematic review synthesizes current research evaluating relationship PAD. Methods A search PubMed, Embase Scopus was conducted up to December 19, 2024, following PRISMA 2020 guidelines. Eligible observational studies assessing PAD in MASLD, MAFLD or NAFLD patients were included. Quality assessment performed independently by two reviewers using Newcastle‐Ottawa Scale (NOS). Results Eleven studies, approximately 848,027 participants, analysed. Most reported increased risk, particularly individuals type 2 diabetes syndrome. Studies criteria demonstrated stronger than those definitions. The presence hepatic fibrosis linked higher risk some studies. However, not all found consistent relationship, few no independent highlighting need for further research. Notably, none included used MASLD criteria. Conclusions Patients MAFLD, comorbidities, may have an elevated severity fibrosis, appears contribute risk. Future should incorporate definitions advanced diagnostic methods clarify guide clinical strategies integrated management.

Язык: Английский

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Protective effects of Ginkgo biloba supplementation on clinical outcomes in metabolic dysfunction-associated steatotic liver disease

Phytomedicine, Год журнала: 2025, Номер 143, С. 156889 - 156889

Опубликована: Май 21, 2025

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global health concern linked to increased risks of cardiovascular disease, chronic kidney (CKD), and premature mortality. Ginkgo biloba has shown potential therapeutic benefits in conditions characterized by metabolic dysfunction. This study aimed evaluate the protective effects supplementation on overall survival (OS) incidence renal outcomes specifically MASLD patients. cohort included 402,476 participants from UK Biobank, categorized into No (SLD) cohorts. users non-users were compared using inverse probability treatment weighting balance baseline characteristics. Clinical assessed Cox proportional hazards models, with subgroup analyses. was associated significantly improved OS [hazard ratio (HR) = 0.79, 95 % confidence interval (CI): 0.64-0.98, p 0.034) reduced events (HR 0.82, CI: 0.66-1.00, 0.012) CKD 0.73, 0.56-0.96, cohort, while no significant observed SLD cohort. Subgroup analyses indicated enhanced older adults, males, individuals BMI ≥ 25 kg/m², diabetic The beneficial pronounced patients advanced fibrosis. patients, particularly high-risk subgroups. These findings highlight as an adjunctive therapy management. first large-scale examine impact clinical MASLD, fibrosis-stratified providing insights its differential across severity.

Язык: Английский

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Chronic Inflammation and Immune Dysregulation in Metabolic-Dysfunction-Associated Steatotic Liver Disease Progression: From Steatosis to Hepatocellular Carcinoma

Biomedicines, Год журнала: 2025, Номер 13(5), С. 1260 - 1260

Опубликована: Май 21, 2025

Background/Objectives: Metabolic-dysfunction-associated steatotic liver disease (MASLD) progresses from hepatic steatosis to hepatocellular carcinoma (HCC) as a result of systemic immunometabolic dysfunction. This review summarizes the key roles innate and adaptive immune mechanisms driving injury, fibrogenesis, carcinogenesis in MASLD. Methods: A comprehensive literature was performed using PubMed identify relevant published studies. Eligible articles included original research clinical studies addressing immunological metabolic MASLD, well emerging therapeutic strategies. Results: We highlight cytokine networks, gut–liver axis, cell reprogramming. Emerging strategies, including inhibitors, anti-fibrotic agents, modulators, nutraceuticals, offer several indications for attenuating MASLD progression reducing prevalence extrahepatic manifestations. Conclusions: Given heterogeneity personalized combination-based approaches targeting both inflammation stress are essential effective management prevention complications.

Язык: Английский

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Association between eGDR and accelerated aging: the mediating role of ePWV

Diabetology & Metabolic Syndrome, Год журнала: 2025, Номер 17(1)

Опубликована: Май 24, 2025

This study examines the association between estimated glucose disposal rate (eGDR) and accelerated aging in middle-aged older adults, with a focus on mediating role of pulse wave velocity (ePWV). Data from 2011 China Health Retirement Longitudinal Study (CHARLS) were analyzed, including participants. Biological age was using Klemera-Doubal method, defined as difference biological chronological age. The eGDR calculated based waist circumference, hypertension status, HbA1c levels, while ePWV mean blood pressure Logistic regression models assessed relationship baseline eGDR, ePWV, aging, adjusting for confounders. A total 8,529 participants (mean 59.31 years) included. significant inverse found aging. Participants lowest quartile had an 81% higher risk compared to those highest (OR = 0.19, 95% CI 0.17-0.22, P < 0.001). Mediation analysis showed that mediated 12.90% (95% 9.20%-16.60%). Reduced insulin sensitivity, indicated by low is factor Vascular measured mediates part this relationship. These findings highlight importance monitoring sensitivity vascular health mitigate age-related risks.

Язык: Английский

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