Sirt1-mediated deacetylation in MAFLD: Mechanisms and therapeutic implications

Metabolic dysfunction-associated fatty liver disease (MAFLD) has emerged as a leading cause of chronic liver disease worldwide, with its pathological mechanisms involving multiple factors such as hepatic steatosis, insulin resistance (IR), oxidative stress, and inflammatory responses. In recent years, Sirtuin 1 (SIRT1) has been recognized as a crucial molecular target for improving MAFLD due to its central role in metabolic regulation and cellular homeostasis. This article reviews the mechanisms by which SIRT1 intervenes in the progression of MAFLD: 1) promoting autophagy and enhancing mitochondrial function; 2) regulating lipid metabolism and oxidative stress-related proteins through deacetylation, thereby improving lipid metabolism disorders and reducing ROS accumulation; 3) suppressing inflammatory responses and alleviating liver inflammation damage; 4) ameliorating IR. Preclinical studies have shown that SIRT1 agonists or gene overexpression can significantly improve the histopathological features of MAFLD in animal models. However, the regulation of SIRT1 is tissue-specific and dose-dependent, and its long-term safety and targeted delivery strategies require further exploration. This article systematically summarizes the molecular mechanisms and therapeutic potential of SIRT1 in MAFLD, providing a theoretical basis for developing novel intervention strategies based on SIRT1 regulation.