MASLD/MASH Learning Center
Discovery of a Potent, Selective, and Multiple His435 Mutation-Sensitive Thyroid Hormone Receptor β Agonist
Beyond selectivity concerns for thyroid hormone receptor β (THR-β) agonists, intolerance to the His435 mutation remains a challenge. Following our previous study, we performed detailed modifications on the 7-position of isoquinoline, specifically targeting the hydrophobic region of the THR-β ligand-binding pocket (LBP). This led to the identification of compound 15n, which showed potent THR-β agonistic activity (EC(50): 3.2 nM), moderately selectivity (∼10-fold), and good activation of multiple...
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MASLD Complicated By Diabetes: Pathophysiology and Emerging Therapies
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a liver manifestation of diabetes that is often associated with obesity and insulin resistance, with hyperglycemia worsening its progression. Recent studies have shown a bidirectional relationship between MASLD and diabetes: MASLD contributes to insulin resistance, and hyperglycemia accelerates the progression of MASLD to metabolic dysfunction-associated steatohepatitis (MASH). Hepatokines upregulated by overnutrition and...
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Identifying Environmental Factors Associated with Significant Fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease/Steatohepatitis
CONCLUSION: Understanding the interaction of health disparities, environmental risk factors, and liver fibrosis in MASLD informs both mechanistic translational studies as well as targeted population screening strategies.
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Resmetirom-eligible population among US adults: An estimation analysis based on NHANES 2017-March 2020
CONCLUSIONS: A substantial proportion of U.S. adults meet eligibility criteria for resmetirom treatment, with estimates varying significantly based on the stringency of selection criteria.
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Resmetirom: A Breakthrough in the Treatment of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
CONCLUSION: MASLD is a significant public health concern driven by metabolic dysfunction. While lifestyle changes remain central to management, Resmetirom offers a promising pharmacological option for patients with moderate to advanced MASH. Further long-term studies are needed to fully establish its safety, effectiveness, and role in preventing advanced liver disease.
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Signature gene expression model for quantitative evaluation of MASH-like liver injury in mice
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a spectrum of chronic pathologic conditions strongly associated with metabolic syndrome and affects approximately 38 % of the global population. Untreated MASLD may progress to metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, and cirrhosis and is currently recognized as one of the main risk factors for hepatocellular carcinoma (HCC). The molecular determinants of MASLD stratification are not clearly defined and...
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Macrophages Atp6v0d2 regulates XBP1-mediated cholesterol metabolism to suppress metabolic dysfunction-associated steatohepatitis progression
CONCLUSION: We uncovered a critical role of myeloid-specific Atp6v0d2 in maintaining hepatic lipid homeostasis and suppressing MASH progression. Targeted activation of Atp6v0d2 as a promising therapeutic strategy for MASH.
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Utilizing Altmetrics to Track Advancements in Noninvasive Tests for MASLD
CONCLUSION: The use of altmetrics alongside traditional metrics may contribute to physicians involved in MASLD care obtaining innovative research information on NIT more quickly.
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p53 and TIGAR promote redox control to protect against metabolic dysfunction-associated steatohepatitis
CONCLUSIONS: Our work demonstrates an important role for the p53-TIGAR axis in protecting against MASH and implicates redox control as a barrier against disease progression that is therapeutically targetable.
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Does the benefit of optimal MASH treatment depend on a reduction in myosteatosis?
The muscle-liver axis, well known in cirrhosis, is also important in the multi-systemic disease known as metabolic dysfunction-associated steatohepatitis (MASH). The convincing results obtained with a triple peroxisome proliferator-activated receptor (PPAR) agonist in this setting confirm this hypothesis, demonstrating a beneficial effect not only on the severity of MASH in terms of steatosis, inflammation and fibrosis, but also in terms of hepatic and muscle insulin sensitivity. The...
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Autoimmunity in MASLD: Focus on autoantibodies, anti-apolipoprotein A1 IgG and G protein-coupled receptors
CONCLUSION: A better understanding of the role of humoral autoimmunity and the interactions among its various components in the metabolic dysfunction underlying MASLD/MASH has the potential to open new perspectives for early detection and therapeutic interventions.
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Changes After Leptin Administration in Partial Lipodystrophy and Factors Associated With Hepatic and Metabolic Response
CONCLUSION: Leptin therapy modulates lipid metabolism, postprandial glucose regulation, and appetite signaling in patients with PL, with responses associated with metabolic parameters and carbohydrate intake.
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