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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Nephrological, Pulmonary, and Dermatological Complications in the Context of MAFLD/NAFLD: A Narrative Review

Metabolites, Journal Year: 2025, Volume and Issue: 15(4), P. 272 - 272

Published: April 14, 2025

Background: The most common cause of chronic liver disease is now known to be non-alcoholic fatty (NAFLD), recently redefined as metabolic-associated (MAFLD). This review aims synthesize current evidence on the pathophysiology and clinical implications nephrological, pulmonary, dermatological manifestations among NAFLD/MAFLD patients. In order find safe efficient treatments, has emerged a primary concern for hepatologists worldwide. Methods: We conducted comprehensive literature from major databases, focusing studies that evaluated extrahepatic NAFLD/MAFLD. Emphasis was placed identifying pathophysiological mechanisms assessing their impact renal, systems. Results: Recent developments in management viral hepatitis have lowered mortality rate associated with disease. However, prevalence continues rise, making significant health future. An increasing percentage patients transplant waiting lists cirrhosis hepatocellular carcinoma due Furthermore, incidence kidney surged, linking higher morbidity, mortality, healthcare costs. Conclusions: underdiagnosed underappreciated, yet its rapidly increasing, raising concerns about potential global epidemic. Given multisystemic impact—extending complications—it crucial develop interdisciplinary strategies early detection effective

Language: Английский

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Association of niacin intake and metabolic dysfunction-associated steatotic liver disease: findings from National Health and Nutrition Examination Survey

BMC Public Health, Journal Year: 2024, Volume and Issue: 24(1)

Published: Oct. 8, 2024

This study aims to explore the relationship between niacin intake and prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) within a large, multi-ethnic cohort.

Language: Английский

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Association Between Ultraprocessed Food Consumption and Metabolic Disorders in Children and Adolescents with Obesity

Nutrients, Journal Year: 2024, Volume and Issue: 16(20), P. 3524 - 3524

Published: Oct. 17, 2024

Background/Objectives: We investigated the effects of ultraprocessed food (UPF) consumption on metabolic disorders (e.g., adiposity, associated steatotic liver disease [MASLD], and insulin resistance) in children adolescents with obesity to improve dietary guidelines public health strategies. Methods: The intake 149 participants (aged 8–17 years) was assessed diaries. NOVA classification system used classify according degree processing. Metabolic outcomes, including fat mass index (FMI), hepatic percentage, resistance, were measured via dual-energy X-ray absorptiometry (DXA), magnetic resonance imaging proton density fraction (MRI-PDFF), biochemical analysis, respectively. Results: Greater UPF from baseline 6-month follow-up significantly increased decreased total cholesterol LDL-cholesterol. positively prevalence MASLD (liver MRI-PDFF ≥ 5%; odds ratio T3 vs. T1 = 1.75; 95% confidence interval [CI] 1.03, 3.00), moderate-to-severe 10%; OR 4.19; CI 1.72, 10.22), resistance (OR 2.44; 1.33, 4.48), after adjusting for covariates. A linear dose-response relationship observed between resistance. Conclusions: strongly obesity, underscoring importance reducing through interventions mitigate risk obesity-related conditions young populations.

Language: Английский

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Associations of Insulin Resistance and High-Sensitivity C-Reactive Protein with Metabolic Abnormalities in Korean Patients with Type 2 Diabetes Mellitus: A Preliminary Study

Metabolites, Journal Year: 2024, Volume and Issue: 14(7), P. 371 - 371

Published: June 30, 2024

We conducted this single-center, retrospective, cohort study to examine whether insulin resistance (IR) and high-sensitivity C-reactive protein (hsCRP) have a relationship with metabolic abnormalities in patients type 2 diabetes mellitus (T2DM). In total of 3758 (

Language: Английский

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Hydrogen-Rich Water (HRW) Reduces Fatty Acid-Induced Lipid Accumulation and Oxidative Stress Damage through Activating AMP-Activated Protein Kinase in HepG2 Cells

Biomedicines, Journal Year: 2024, Volume and Issue: 12(7), P. 1444 - 1444

Published: June 28, 2024

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by excessive fat accumulation in the liver. Intracellular oxidative stress induced lipid leads to various hepatocellular injuries including fibrosis. However, no effective method for mitigating MASLD without substantial side effects currently exists. Molecular hydrogen (H

Language: Английский

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Pathophysiological Relationship between Type 2 Diabetes Mellitus and Metabolic Dysfunction-Associated Steatotic Liver Disease: Novel Therapeutic Approaches

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(16), P. 8731 - 8731

Published: Aug. 10, 2024

Type 2 diabetes mellitus (T2DM), often featuring hyperglycemia or insulin resistance, is a global health concern that increasing in prevalence the United States and worldwide. A common complication metabolic dysfunction-associated steatotic liver disease (MASLD), hepatic manifestation of syndrome also rapidly prevalence. The majority patients with T2DM will experience MASLD, likewise, individuals MASLD are at an increased risk for developing T2DM. These two disorders may act synergistically, part due to lipotoxicity inflammation within liver, among other causes. However, pathophysiological mechanisms by which this occurs unclear, as how improvement one disorder can ameliorate other. This review aims discuss pathogenic interactions between T2D highlight novel therapeutic targets ongoing clinical trials treatment these diseases.

Language: Английский

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Hepatokines and MASLD: The GLP1-Ras-FGF21-Fetuin-A Crosstalk as a Therapeutic Target

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(19), P. 10795 - 10795

Published: Oct. 8, 2024

The introduction of the term “Metabolic Steatotic Liver Disease” (MASLD) underscores critical role metabolic dysfunction in development and progression chronic liver disease emphasizes need for strategies that address both its comorbidities. In recent years, a liver-focused perspective has revealed altered endocrine function fatty is key contributor to dysregulation observed MASLD. Due secretory capacity, liver’s increased production proteins known as “hepatokines” been linked insulin resistance, explaining why MASLD often precedes other organs ultimately contributes systemic disease. Among these hepatokines, fibroblast growth factor 21 (FGF21) fetuin-A play central roles regulating abnormalities associated with MASLD, their dysregulated secretion response stress implicated This review postulates modulation by GLP1-Ras may mediate beneficial effects drugs, which have attention emerging pharmacotherapy By discussing crosstalk between GLP1-Ras-FGF21-fetuin-A, this hypothesizes possible novel GLP1-FGF21 dual agonist contribute management diseases. Although research needed go into details crosstalk, topic help researchers explore mechanisms type manage

Language: Английский

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Marine-Derived Phosphoeleganin and Its Semisynthetic Derivative Decrease IL6 Levels and Improve Insulin Signaling in Human Hepatocellular Carcinoma Cells

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(11), P. 6039 - 6039

Published: May 30, 2024

Marine natural products constitute a great source of potential new antidiabetic drugs. The aim this study was to evaluate the role phosphoeleganin (PE), polyketide purified from Mediterranean ascidian Sidnyum elegans, and its derivatives PE/2 PE/3 on insulin sensitivity in human hepatocellular carcinoma (HepG2) cells. In our experiments, stimulates phosphorylation receptor (INSR) AKT by 1.5- 3.5-fold, respectively, whereas presence PE, PE/2, PE/3, induced INSR is increased 2.1-, 2-, 1.5-fold 7.1-, 6.0-, 5.1-fold, respectively. Interestingly, PE have an additive effect insulin-mediated reduction phosphoenolpyruvate carboxykinase (PEPCK) expression. Finally, but not decrease interleukin 6 (IL6) secretion expression before after palmitic acid incubation, while high glucose (HG), only reduces IL6. Levels other cytokines are significantly affected derivates. All these data suggest that synthetic-derived compound, IL6 improve hepatic signaling. As impairs action, it could be hypothesized inhibiting IL6, may pathway.

Language: Английский

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Exploring Fibrosis Pathophysiology in Lean and Obese Metabolic-Associated Fatty Liver Disease: An In-Depth Comparison

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 7405 - 7405

Published: July 5, 2024

While obesity-related nonalcoholic fatty liver disease (NAFLD) is linked with metabolic dysfunctions such as insulin resistance and adipose tissue inflammation, lean NAFLD more often progresses to fibrosis even in the absence of syndrome. This review aims summarize current knowledge regarding mechanisms NAFLD. The most commonly used models include a methionine/choline-deficient (MCD) diet, high-fat diet carbon tetrachloride (CCl4), high-fructose high-cholesterol diet. major pro-fibrogenic increased activation extracellular signal-regulated kinase (ERK) pathway, elevated expression α-smooth muscle actin (α-SMA), collagen type I, TGF-β, modulation fibrogenic markers tenascin-X metalloproteinase inhibitors. Additionally, macrophage signaling pathways promoting hepatic stellate cell (HSC) further contributes development. Animal cannot cover all clinical features that are evident patients or obese NAFLD, implicating need for novel models, well deeper comparisons experimental studies. Having mind prevalence patients, by addressing specific pathways, studies can reveal new targeted therapies along biomarkers early detection enhancement management patients.

Language: Английский

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