RESUMO
Metabolic dysfunction-associated diseases often refer to various diseases caused by metabolic problems such as glucose and lipid metabolism disorders. With the improvement of living standards, the increasing prevalence of metabolic diseases has become a severe public health problem, including metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-related liver disease (ALD), diabetes and obesity. These diseases are both independent and interdependent, with complex and diverse molecular mechanisms. Therefore, it is urgent to explore the molecular mechanisms and find effective therapeutic targets of these diseases. MicroRNAs (miRNAs) have emerged as key regulators of metabolic homoeostasis due to their multitargets and network regulatory properties within the past few decades. In this review, we discussed the latest progress in the roles of miRNA-mediated regulatory networks in the development and progression of MASLD, ALD, diabetes and obesity.
Assuntos
Doenças Metabólicas , MicroRNAs , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Animais , Doenças Metabólicas/metabolismo , Doenças Metabólicas/terapia , Doenças Metabólicas/genética , Obesidade/metabolismo , Obesidade/genética , Diabetes Mellitus/metabolismo , Diabetes Mellitus/genética , Diabetes Mellitus/terapia , Fígado Gorduroso/metabolismo , Fígado Gorduroso/genética , Fígado Gorduroso/terapia , Fígado Gorduroso/etiologiaRESUMO
Alcohol-related liver disease (ALD) and metabolic dysfunction-associated steatotic liver disease (MASLD), two main types of steatotic liver disease (SLDs), are characterized by a wide spectrum of several different liver disorders, including simple steatosis, steatohepatitis, cirrhosis, and hepatocellular carcinoma. Multiple immune cell-mediated inflammatory responses not only orchestrate the killing and removal of infected/damaged cells but also exacerbate the development of SLDs when excessive or persistent inflammation occurs. In recent years, single-cell and spatial transcriptome analyses have revealed the heterogeneity of liver-infiltrated immune cells in ALD and MASLD, revealing a new immunopathological picture of SLDs. In this review, we will emphasize the roles of several key immune cells in the pathogenesis of ALD and MASLD and discuss inflammation-based approaches for effective SLD intervention. In conclusion, the study of immunological mechanisms, especially highly specific immune cell population functions, may provide novel therapeutic opportunities for this life-threatening disease.
Assuntos
Fígado Gorduroso , Humanos , Animais , Fígado Gorduroso/imunologia , Fígado Gorduroso/terapia , Inflamação/imunologia , Fígado Gorduroso Alcoólico/imunologia , Fígado Gorduroso Alcoólico/terapia , Fígado/patologia , Fígado/imunologia , Fígado/metabolismoRESUMO
Metabolic disorders are currently threatening public health worldwide. Discovering new targets and developing promising drugs will reduce the global metabolic-related disease burden. Metabolic disorders primarily consist of lipid and glucose metabolic disorders. Specifically, metabolic dysfunction-associated steatosis liver disease (MASLD) and alcohol-associated liver disease (ALD) are two representative lipid metabolism disorders, while diabetes mellitus is a typical glucose metabolism disorder. In this review, we aimed to summarize the new drug candidates with promising efficacy identified in clinical trials for these diseases. These drug candidates may provide alternatives for patients with metabolic disorders and advance the progress of drug discovery for the large disease burden.