Sex dimorphism and metabolic profiles in management of metabolic-associated fatty liver disease

Metabolic-associated fatty liver disease (MAFLD) refers to the build-up of fat in the liver associated with metabolic dysfunction and has been estimated to affect a quarter of the population worldwide. Although metabolism is highly influenced by the effects of sex hormones, studies of sex differences in the incidence and progression of MAFLD are scarce. Metabolomics represents a powerful approach to studying these differences and identifying potential biomarkers and putative mechanisms. First, metabolomics makes it possible to obtain the molecular phenotype of the individual at a given time. Second, metabolomics may be a helpful tool for classifying patients according to the severity of the disease and obtaining diagnostic biomarkers. Some studies demonstrate associations between circulating metabolites and early and established MAFLD, but little is known about how metabolites relate to and encompass sex differences in disease progression and risk management. In this review, we will discuss the epidemiological metabolomic studies for sex differences in the development and progression of MAFLD, the role of metabolic profiles in understanding mechanisms and identifying sex-dependent biomarkers, and how this evidence may help in the future management of the disease.