Unraveling the Metabolic Pathways Between Metabolic-Associated Fatty Liver Disease (MAFLD) and Sarcopenia.

Metabolic-Associated Fatty Liver Disease (MAFLD) is a public health concern that is constantly expanding, with a fast-growing prevalence, and it affects about a quarter of the world's population. This condition is a significant risk factor for cardiovascular, hepatic, and oncologic diseases, such as hypertension, hepatoma, and atherosclerosis. Sarcopenia was long considered to be an aging-related syndrome, but today, it is acknowledged to be secondarily related to chronic diseases such as metabolic syndrome, cardiovascular conditions, and liver diseases, among other comorbidities associated with insulin resistance and chronic inflammation, besides inactivity and poor nutrition. The physiopathology involving MAFLD and sarcopenia has still not been solved. Inflammation, oxidative stress, mitochondrial dysfunction, and insulin resistance seem to be some of the keys to this relationship since this hormone target is mainly the skeletal muscle. This review aimed to comprehensively discuss the main metabolic and physiological pathways involved in these conditions. MAFLD and sarcopenia are interconnected by a complex network of pathophysiological mechanisms, such as insulin resistance, skeletal muscle tissue production capacity, chronic inflammatory state, oxidative stress, and mitochondrial dysfunction, which are the main contributors to this relationship. In addition, in a clinical analysis, patients with sarcopenia and MAFLD manifest more severe hepatitis fibrosis when compared to patients with only MAFLD. These patients, with both disorders, also present clinical improvement in their MAFLD when treated for sarcopenia, reinforcing the association between them. Lifestyle changes accompanied by non-pharmacological interventions, such as dietary therapy and increased physical activity, undoubtedly improve this scenario.