Research progress on the mechanistic pathways and biomarkers of therapeutic drugs for metabolic-associated steatotic liver disease

Objective: The incidence of metabolic-associated steatotic liver disease (MASLD) remains persistently high, and there is a lack of specific therapeutic drugs in clinical practice. Elucidating the mechanistic pathways of therapeutic drugs for MASLD and exploring biomarkers with high specificity and sensitivity are of great significance for the precise diagnosis and treatment of the disease. The present study aims to review the research progress in this relevant field. Methods: We systematically collated recent domestic and international literature on the mechanistic pathways of therapeutic drugs and biomarkers for MASLD, and analyzed the mechanisms of action, key signaling pathways of different therapeutic drugs, as well as the characteristics of various biomarkers. Results: Drugs for MASLD treatment mainly exert their effects by regulating lipid metabolism, ameliorating insulin resistance (IR), and inhibiting inflammation and oxidative stress. For instance, peroxisome proliferator-activated receptors (PPARs) agonists improve lipid metabolism and IR via the PPARs signaling pathway; adenosine monophosphate-activated protein kinase (AMPK) activators enhance insulin sensitivity through the AMPK signaling pathway; and anti-inflammatory drugs alleviate inflammatory injury by inhibiting the nuclear factor kappa-B (NF-κB) signaling pathway. Relevant biomarkers include metabolomic biomarkers (lipidome, amino acidome, etc.), inflammatory biomarkers (tumor necrosis factor-α[TNF-α], interleukin-6 [IL-6], etc.), liver fibrosis biomarkers (procollagen type III [Pro-C3], enhanced liver fibrosis [ELF] score, etc.) and non-coding RNA biomarkers, each exhibiting distinct values in disease diagnosis and therapeutic efficacy evaluation. Conclusion: At present, the core mechanistic pathways of a variety of MASLD therapeutic drugs and potential biomarkers have been identified, yet problems such as insufficient targeting in drug research and development and difficulties in the clinical translation of biomarkers still exist. In the future, it is necessary to further deepen mechanistic research, promote the development of precision therapeutic drugs and the clinical application of biomarkers, so as to provide more reliable theoretical and practical support for the diagnosis and treatment of MASLD.