PR002295 (Project)

Description:Excessive caloric intake is a primary driver of metabolic dysfunction-associated steatotic liver disease (MASLD), and this has been recapitulated in mice fed a high-fat diet. In 2023, the global prevalence of MASLD was estimated at 30%, with high incidences affecting wealthy urbanised countries. This implication of hypercaloric diets can also perturb metabolism and function of extrahepatic tissues such as heart, kidney and skeletal muscle. These effects that can take place in extrahepatic tissues are still poorly understood in terms of metabolic alterations and physiology, and represent an important point of improvement in the knowledge gap that connects early stage MASLD with other obesity related comorbidities, such as type 2 diabetes, insulin resistance, cardiovascular and renal complications, and overall, with the so known metabolic syndrome. In this study, we aimed to evaluate the potential of using metabolomics to unravel the effects and interactions taking place in a diet-induced MASLD model related to the development of the disorder. Black-6 mice were subjected to either a control diet or a high-fat diet for 18 weeks, from which at the end their heart, kidney and skeletal muscle metabolites were extracted. The metabolites, divided into aqueous and lipophilic fractions, were acquired by 1H-NMR, and then processed using a untargeted Metabolomics and Lipidomics analysis approach, to identify key changes occurring between control and high-fat diet in these models. These results added important information to better understand the link between early onset MASLD and the Metabolic Syndrome and its comorbidities, though several metabolic changes in the extrahepatic tissues, namely in ectopic fat deposition and alterations to Randle cycle and gut microbiota activity.