Transcriptomic Landscape Analysis Reveals a Persistent DNA Damage Response in Metabolic Dysfunction-associated Steatohepatitis Post-dietary Intervention.

Background And Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) and its more advanced form, metabolic dysfunction-associated steatohepatitis, have emerged as the most prevalent liver diseases worldwide. Currently, lifestyle modification is the foremost guideline-recommended management strategy for MASLD. However, it remains unclear which detrimental signals persist in MASLD even after disease remission.

Sestrin2 maintains hepatic immune homeostasis and redox balance partially via inhibiting RIPK3-mediated necroptosis in metabolic dysfunction-associated steatohepatitis.

Background & Aims: Necroptosis, a novel type of programmed cell death, is intricately associated with inflammatory response. Currently, most studies focus on the activation of necroptosis, while the mechanisms underlying the negative regulation of necroptosis remain poorly understood.

Methods: The effects of sestrin2 (SESN2) overexpression or knockdown on the regulation of necroptosis were assessed in the TNFα/Smac-mimetic/Z-VAD-FMK (T/S/Z)-induced necroptosis model and palmitic acid (PA)-induced lipotoxicity model.

Peripheral immune cells in NAFLD patients: A spyhole to disease progression.

Nonalcoholic fatty liver disease (NAFLD) is a worldwide leading cause of chronic liver disease, but we still lack ideal non-invasive tools for diagnosis and evaluation of nonalcoholic steatohepatitis (NASH) and related liver fibrosis in NAFLD population. Systemic immune dysregulations such as metabolic inflammation are believed to play central role in the development of NAFLD, signifying the hope of utilizing quantitative and phenotypic changes in peripheral immune cells among NAFLD patients as a diagnostic tool of NASH and fibrosis. In this review, we summarize the known changes in peripheral immune cells from NAFLD/NASH patients and their potential relationship with NAFLD and NASH progression.

Non-alcoholic fatty liver disease to metabolic dysfunction-associated fatty liver disease: Conceptual changes for clinicians, researchers and patients.

Non-alcoholic fatty liver disease (NAFLD) is now the most common etiology of chronic liver disease threatening global public health. However, the name "NAFLD" is no longer appropriate with the change of time. Recently, a new term, "metabolic dysfunction-associated fatty liver disease" has been proposed by an international panel of experts, which implies profound conceptual changes in terms of its metabolism-related etiology and disease heterogeneity.

Prolyl endopeptidase gene disruption attenuates high fat diet-induced nonalcoholic fatty liver disease in mice by improving hepatic steatosis and inflammation.

Background: Prolyl endopeptidase (PREP) is a serine endopeptidase that regulates inflammatory responses. PREP inhibitors can reduce hepatocyte lipid accumulation and may participate in the progression of nonalcoholic fatty liver disease (NAFLD). We investigated whether disruption of PREP regulates hepatic steatosis and inflammation in mice with NAFLD.