Normalizing a hyperactive mTOR initiates muscle growth during obesity

Functional impairment is a major concern in the obese population, leading to reductions in everyday activities [1]. Obesity-related reductions in muscle function are due to a loss of muscle mass (i.e. sarcopenia), which occurs largely from an imbalance between the rates of protein synthesis and degradation [2,3]. A major controlling mechanism for muscle peptide/protein formation is messenger RNA (mRNA) translation. Initiation of translation is regulated by hormones and the diet through alterations in the mammalian Target of Rapamycin (mTOR) [4,5,6]. Despite hyperactivation of the growth-promoting, nutrient-sensing mTOR pathway, atrophy persists in obese muscle [7]. Chronic hyperactivation of mTOR signaling is atypical outside of disease states, such as obesity, dyslipidemia, hypercholesterolemia, or certain types of cancer. With the obesity rate growing at an alarming rate, there is a critical need to determine how obesity-related sarcopenia can be limited, since metabolic homeostasis is positively linked to muscle mass.