Improvement in insulin sensitivity following weight loss in obese patients is associated with circulating myostatin

Increased levels of myostatin, a negative regulator of skeletal muscle development, have been shown in obesity and associated with dysregulated energy metabolism. There is growing interest on dietary factors behind muscle training, that regulate circulating myostatin levels. The aim of the study was to assess the effect of weight loss after a 3-month hypocaloric diet on plasma myostatin concentration in obese patients and to examine whether the myostatin level affects the effectiveness of the hypocaloric diet. The study involved 73 obese patients using hypocaloric (HCD) or control normocaloric (NCD) diet. Body weight and composition as well as biomarkers of glucose and lipid metabolism and plasma myostatin were measured before and after 3-month diet. The use of a 3-month hypocaloric diet, without changing of physical activity, markedly reduced BMI (-7.7% in HCD vs. -0.9% in NCD), body fat, influenced postprandial insulin sensitivity and improved plasma lipid profile. The dietary intervention did not influence muscle mass as well as plasma myostatin levels in the whole cohort, although the highest myostatin levels were normalized after 3 month to average values. Only the group with initially higher levels of myostatin (>21.18 ng/mL) achieved an improvement in carbohydrate metabolism. Results showed that obese patients who experienced a decrease in plasma myostatin concentration after a 3-month HCD had greater improvement in glucose metabolism, fasting and postprandial, than obese patients without reduction in circulating myostatin (correlations of Δ myostatin with Δ fasting glucose Rho=0.42, p<0.001; Δ myostatin with Δ glucose AUC OGTT Rho=0.33, p=0.005). In conclusion, increased circulating myostatin may be involved in the development of insulin resistance but does not significantly affect lipid complications in obese patients. A hypocaloric diet may only affect the highest myostatin values in obese individuals.