MOTS-c Microprotein Prevents Muscle Wasting and Fat Buildup from Immobility

Prolonged periods of immobilization, such as during bed rest, space travel, or post-surgical recovery, lead to rapid and severe skeletal muscle atrophy (muscle wasting). A significant complication of this atrophy is increased lipid infiltration within the muscle, which further impairs muscle function and recovery. Despite the prevalence and impact of this condition, effective therapeutic strategies to counteract both muscle loss and fat accumulation are limited. This study specifically addresses the knowledge gap regarding novel interventions that can simultaneously mitigate immobilization-induced skeletal muscle atrophy and suppress detrimental intramuscular lipid infiltration.

The study found that MOTS-c treatment significantly attenuated muscle loss and lipid accumulation in immobilized limbs. Specifically, MOTS-c-treated mice exhibited 28% less soleus muscle mass reduction compared to untreated immobilized controls (p<0.001), demonstrating a potent protective effect against atrophy. Furthermore, intramuscular lipid content, a key indicator of fatty infiltration, was dramatically reduced by 45% in the MOTS-c group compared to immobilized controls (p<0.001). This protective effect was associated with enhanced mitochondrial biogenesis, evidenced by a 2.3-fold increase in PGC-1α expression, a master regulator of mitochondrial content, and a 1.8-fold increase in mitochondrial respiration capacity. MOTS-c treatment not only preserved muscle mass but also significantly suppressed detrimental lipid infiltration, offering a dual therapeutic benefit against immobilization-induced skeletal muscle atrophy. Additionally, MOTS-c reduced markers of inflammation by 35% and oxidative stress by 22% within the atrophying muscle, suggesting a broader protective mechanism beyond direct mitochondrial effects.