MASLD/MASH Learning Center
The impact of semaglutide on liver fat assessed by serial cardiac CT scans in patients with type 2 diabetes: Results from STOP trial
CONCLUSION: In type 2 diabetes patients with hepatic steatosis, treatment with semaglutide resulted in a significant improvement in fatty liver reduction when compared to placebo.
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Neurotensin promotes hepatic steatosis by regulating lipid uptake and mitochondrial adaptation in hepatocytes
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a multifactorial disease characterized by hepatic steatosis. Mitochondrial dysfunction resulting in the incomplete digestion of surplus fat is one of the key factors that lead to hepatic steatosis but the reason for this remains unclear. We investigated the role of neurotensin (NTS), a gut hormone, in inducing maladaptive fat metabolism in steatotic liver. We identify CD36 and PGC1α, two critical drivers of MASLD, as direct NTS...
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Intestinal Activation of LXRalpha Counteracts Metabolic-Associated Steatohepatitis Features in Mice
Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global health problem and the discovery of drugs is challenging. In this study, we aimed to investigate the effects of intestinal activation of the liver X receptor (LXR)α on MASH. Methods: An intestinal-specific LXRα activation model in mice was established and subjected to MASH development by combining a Western diet and carbon tetrachloride. Lipid metabolism, reverse cholesterol transport...
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Astrocyte Elevated Gene-1/Metadherin (AEG-1/MTDH): A Promising Molecular Marker and Therapeutic Target for Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths. The 5-year survival rate has been estimated to be less than 20% while its incidence rates have more than tripled since the 1980s. Astrocyte elevated gene-1/Metadherin (AEG-1/MTDH) has been demonstrated to have an influential role in HCC progression and the development of an aggressive phenotype. AEG-1 has been shown to be upregulated in many cancers, including HCC. Studies have shown that it plays a crucial...
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Molecular Landscape and Diagnostic Model of MASH: Transcriptomic, Proteomic, Metabolomic, and Lipidomic Perspectives
Metabolic dysfunction-associated steatohepatitis (MASH), a progressive form of fatty liver disease, presents a significant global health challenge. Despite extensive research, fully elucidating its complex pathogenesis and developing accurate non-invasive diagnostic tools remain key goals. Multi-omics approaches, integrating data from transcriptomics, proteomics, metabolomics, and lipidomics, offer a powerful strategy to achieve these aims. This review summarizes key findings from multi-omics...
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Discovery of the first-in-class FABP/PPAR multiple modulator for the treatment of metabolic dysfunction-associated steatohepatitis
Metabolic dysfunction-associated steatohepatitis (MASH) is a complex metabolic syndrome, and the development of new drugs is urgently needed. Fatty acid binding proteins (FABPs) and peroxisome proliferator-activated receptors (PPARs) play an important role in the regulation of lipid absorption, metabolism and inflammation. Considering the synergistic effect of FABP and PPAR in the regulation of MASH pathophysiology, the development of FABP/PPAR multiple modulators might be a promising anti-MASH...
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Salsalate improves the anti-tumor efficacy of lenvatinib in MASH-driven hepatocellular carcinoma
CONCLUSIONS: These data indicate that combining LEN and SAL, which exert distinct effects leading to improvements in the liver microenvironment (steatosis, angiogenesis, and fibrosis) and inhibition of tumor proliferation, may have therapeutic potential for MASH-driven HCC.
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Estimating the clinical and healthcare burden of metabolic dysfunction-associated steatohepatitis in England: a retrospective cohort study using routinely collected healthcare data from 2011 to 2020
CONCLUSION: HCRU and costs associated with MASH are higher among patients who have cardiometabolic comorbidities or who progress to advanced disease stages. Therefore, efforts to detect cases early and prevent disease progression could reduce healthcare burden.
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New insights into biomarkers and risk stratification to predict hepatocellular cancer
Hepatocellular carcinoma (HCC) is the third major cause of cancer death worldwide, with more than a doubling of incidence over the past two decades in the United States. Yet, the survival rate remains less than 20%, often due to late diagnosis at advanced stages. Current HCC screening approaches are serum alpha-fetoprotein (AFP) testing and ultrasound (US) of cirrhotic patients. However, these remain suboptimal, particularly in the setting of underlying obesity and metabolic...
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Ketogenesis mitigates metabolic dysfunction-associated steatotic liver disease through mechanisms that extend beyond fat oxidation
The progression of metabolic dysfunction-associated steatotic liver disease (MASLD) to metabolic dysfunction-associated steatohepatitis (MASH) involves alterations in both liver-autonomous and systemic metabolism that influence the liver's balance of fat accretion and disposal. Here, we quantify the contributions of hepatic oxidative pathways to liver injury in MASLD-MASH. Using NMR spectroscopy, UHPLC-MS, and GC-MS, we performed stable-isotope tracing and formal flux modeling to quantify...
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Identification of MEOX1 as a potential target in metabolic dysfunction-associated steatohepatitis-related liver fibrosis
BackgroundThe mechanisms underlying the occurrence and progression of metabolic dysfunction-associated steatohepatitis (MASH)-related liver fibrosis remains poorly understood. This study aims to identify key transcription factors involved in the development of liver fibrosis in MASH patients, thereby providing potential targets for drug discovery.MethodsMicroarray data were retrieved from liver biopsy specimens of MASH patients exhibiting varying stages of fibrosis via the Gene Expression...
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Lipid Dysmetabolism in Canine Chronic Liver Disease: Relationship Between Clinical, Histological and Immunohistochemical Features
Chronic liver diseases (CLDs) in dogs are progressive conditions that often lead to liver failure. Metabolic dysfunctions such as cholestasis, obesity, hyperlipidemia, and endocrine disorders play a key role in human liver diseases like MASLD (Metabolic Dysfunction Associated Steatotic Liver Disease) and MASH (Metabolic Dysfunction Associated Steatohepatitis), but their significance in canine CLDs is poorly understood. This study aims to evaluate the association between hepatic lipid...
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