Transcription factor EB: A potential integrated network regulator in metabolic-associated cardiac injury.

With the worldwide pandemic of metabolic diseases, such as obesity, diabetes, and non-alcoholic fatty liver disease (NAFLD), cardiometabolic disease (CMD) has become a significant cause of death in humans. However, the pathophysiology of metabolic-associated cardiac injury is complex and not completely clear, and it is important to explore new strategies and targets for the treatment of CMD. A series of pathophysiological disturbances caused by metabolic disorders, such as insulin resistance (IR), hyperglycemia, hyperlipidemia, mitochondrial dysfunction, oxidative stress, inflammation, endoplasmic reticulum stress (ERS), autophagy dysfunction, calcium homeostasis imbalance, and endothelial dysfunction, may be related to the incidence and development of CMD. Transcription Factor EB (TFEB), as a transcription factor, has been extensively studied for its role in regulating lysosomal biogenesis and autophagy. Recently, the regulatory role of TFEB in other biological processes, including the regulation of glucose homeostasis, lipid metabolism, etc. has been gradually revealed. In this review, we will focus on the relationship between TFEB and IR, lipid metabolism, endothelial dysfunction, oxidative stress, inflammation, ERS, calcium homeostasis, autophagy, and mitochondrial quality control (MQC) and the potential regulatory mechanisms among them, to provide a comprehensive summary for TFEB as a potential new therapeutic target for CMD. The integrated regulatory role of TFEB in metabolic-associated cardiac injury. When the body encounters metabolic disorders, it causes a series of pathophysiological reactions including insulin resistance, hyperglycemia, hyperlipidemia, endothelial dysfunction, oxidative stress, inflammation, endoplasmic reticulum stress, impaired calcium handling, autophagy dysregulation, mitochondrial dysfunction, ultimately leading to metabolic-associated cardiac injury. TFEB not only plays an important regulatory role in autophagy but also shows great potential in regulating insulin resistance, oxidative stress, inflammation, endoplasmic reticulum stress, calcium homeostasis, lipid metabolism, endothelial function, and mitochondrial quality control.