(P15-045-24) Hepatic Amino Acid Alterations in Individuals With Obesity and Metabolic Dysfunction-Associated Steatotic Liver Disease

Objectives: Deregulation of amino acid (AA) metabolism has been reported in various pathological conditions, including metabolic diseases (obesity and diabetes), cardiovascular diseases, autoimmune diseases, neurological disorders, and cancer. However, the role of alterations in AA levels in chronic liver disorders commonly related to excess caloric consumption, unhealthy diet, and sedentary lifestyle, including metabolic dysfunction-associated steatotic liver disease (MASLD) remains largely unexplored. Despite the relatively high incidence of MASLD in the population and its potential detrimental effects on human health, this liver disease is still not fully understood from a pathophysiological perspective. Therefore, in this this study we aimed to evaluate the hepatic AA composition in patients with different stages of MASLD, and their relationship with MASLD-related risk factors.

Methods: This was a case-control study in patients with obesity undergoing bariatric surgery at the Virgen de la Arrixaca University Hospital (Murcia, Spain) between January 2020 and December 2021. Participants were distributed in three groups: no MASLD (n = 11), steatotic liver disease (n = 9), and metabolic dysfunction-associated steatohepatitis (MASH; n = 20). Hepatic AA levels in human liver tissue were evaluated by ultra-performance liquid chromatography high-resolution time-of-flight mass spectrometry.

Results: The hepatic AA profiles were significantly altered in patients with MASLD. More specifically, we found a significant reduction in hepatic aspartic acid and a significantly increase in hepatic lysine in liver samples of patients with MASLD compared to those without MASLD. Further comparison between MASLD patients revealed a significant increase in hepatic levels of arginine and cystine in MASH samples compared to livers with simple steatosis. In addition, hepatic levels of arginine, lysine and cystine positively correlated with histopathological diagnosis and other MASLD-related parameters (i.e., transaminases).

Conclusions: Alterations in hepatic AA levels in MASLD patients could have translational relevance in understanding the onset of this disease.

Funding Sources: Institute of Health Carlos III (Madrid, Spain)