A feature of several diseases (cancer, sepsis, heart failure, kidney diseases…) is a catabolic state leading to muscle wasting, and consequently muscle weakness. The main function of skeletal muscle is to provide power and strength for locomotion and posture. However, skeletal muscles being the only reservoir of amino acids (AAs) in the body, muscle proteins can be degraded during chronic diseases to furnish AAs to the other organs (mainly viscera) [1]. However, an uncontrolled and sustained muscle wasting impairs movement, decreases autonomy, but also induces detrimental metabolic alterations to other organs and increases morbidity. In the whole, these disorders lead to patient frailty and impair the efficacy of treatments (e.g. chemotherapy). Proteolysis activation for rapid degradation of contractile proteins is the main cause of muscle atrophy, the ubiquitin proteasome system (UPS) and autophagy being the main proteolytic systems involved. The UPS muscle-specific ring finger-1 (MuRF1) E3 ligase is so far the only known E3 ligase able to target the contractile proteins (actin, myosins, etc.) for their degradation [2]. Inhibiting MuRF1 is thus a potential strategy for sparing muscle mass in patients suffering from chronic diseases. One can consider that maintaining muscle protein mass by using strong inhibitors of MuRF1 (although this kind of inhibitors are not available yet) may compromise AA availability to other organs, thus impairing functions such as liver gluconeogenesis and production of inflammatory proteins. To address this hypothesis, we used MuRF1-KO mice that mimic total inhibition of this E3 ligase. Mice were subjected to dexamethasone treatment (Dex), which is known to drastically increase both gluconeogenesis and protein synthesis in the liver, while it induces UPS-dependent muscle atrophy through increased MuRF1 expression. We found that while muscle mass was spared in MuRF1-KO mice, both glycogen and lipids dramatically accumulated in the liver compared to WT Dex-treated mice. Using Fourier Transform Infrared (FTIR) spectrometry, we also found profound alterations of lipid, carbohydrates and protein content in Dex-treated liver from MuRF1-KO mice. Finally, we observed an altered profile of mTOR kinase targets in the livers of MuRF1-KO mice, suggesting a depressed protein synthesis in Dex-treated KO mice when compared to WT animals. Altogether, this suggests that altering MuRF1 levels for preserving muscle mass should take into account potential side effects on other organs.