OP- 14 ENHANCED MUSCLE MASS MITIGATES MASLD IN MYOSTATIN KNOCKOUT MICE WITHOUT IMPACTING EXERCISE PERFORMANCE

No Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is linked to sarcopenia and exacerbated by obesity. Individuals with higher relative skeletal muscle mass are protected against MASLD or more likely to see its resolution, regardless of demographic and health-related factors. This study examines the effects of muscle mass enhancement, independent of exercise, on MASLD progression using myostatin knockout (Mstn-KO) mice, which are genetically modified to exhibit increased muscle mass due to myostatin deficiency. 11-week-old Mstn-KO mice and their wild-type counterparts were fed a Western diet (WD) for 24 weeks to induce MASLD. Parameters assessed included liver steatosis through histological analysis, muscle mass via MRI and histological cross-sectional area, exercise performance through treadmill tests, and muscle strength measured by electrophysiology. Mstn-KO mice showed significantly reduced liver steatosis (-20%) and increased muscle mass (+30%) compared to wild-type controls. Additionally, liver pro-inflammatory cytokines such as IL-1β and TNF-α were decreased in Mstn-KO mice, along with lower expression of lipogenesis-related genes, indicating a protective effect against MASLD progression. Histological assessments showed less hepatic lipid accumulation and inflammation in Mstn-KO mice, correlating with decreased myosteatosis and an enhanced cross-sectional area of muscle fibers. Muscle mass was measured by bioimpedance analysis, and paravertebral muscle area was evaluated using MRI. Electrophysiological measures indicated increased tetanic strength in Mstn-KO mice. Despite these physiological improvements, treadmill test results did not show significant differences in exercise performance between Mstn-KO and wild-type groups, suggesting that muscle mass improvement did not translate into enhanced exercise capacity. These results indicate that Mstn-KO mice are protected against muscle atrophy and MASLD progression. Our findings suggest that increased muscle mass, independent of exercise performance, can significantly ameliorate MASLD histology. Mstn-KO mice serve as a valuable model for exploring muscle-liver crosstalk in liver diseases, indicating potential treatment pathways that do not rely on exercise enhancement.