Nutritional modulation of the mTORC1 pathway in muscle: differential effect according to muscle and sex

Numerous studies have focused on nutrient-driven regulation of muscle metabolism/homeostasis through the mammalian target of rapamycin complex 1 (mTORC1) pathway, but their results fail to converge, perhaps due to differences in mTORC1 pathway protein studied, muscle type, and/or sex. The aim of this work was to study the influence of these factors on mTORC1 pathway activation in response to food intake. Rats (16 male and 16 female) were fasted for 20 h and then were randomized into two groups: a postabsorptive group in which the animals were euthanized in the fasted state and a postprandial group in which the animals were euthanized 30 min after food intake (10 g). Plasma glucose, insulin, and amino acids were assayed. Muscles (extensor digitorum longus, tibialis, soleus, gastrocnemius and plantaris) were removed and Western blotted to analyze the activation of the mTORC1 pathway [phosphorylation of Akt, 4E-binding protein 1 (4E-BP1), and S6K1]. Levels of Akt, 4E-BP1, and S6K1 activation were compared between muscles and by sex in different nutritional states, and a Kruskal-Wallis test was performed to find statistically significant differences.Food intake led to an increase in plasma concentrations of glucose, insulin, and total amino acids (<i>P</i> < 0.0001). Levels of Akt, 4E-BP1, and S6K1 activation differed significantly between muscles and by sex and nutritional state. Different phosphorylation sites in the same muscle were not correlated with each other. These results suggest that mTORC1 activation level is sensitive to muscle type, sex, and nutritional state. Studies on this signal transduction pathway therefore require an individualized approach, considering all the factors that may affect it.<b>NEW & NOTEWORTHY</b> This work demonstrates the complexity of the regulation of the mTOR pathway depending on the protein, muscle, sex, and nutritional status studied. This systemic approach is very little/not considered in the articles.