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

Abstract

Numerous studies have focused on nutrient-driven regulation of muscle metabolism/homeostasis through the 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 hours 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 activation of the mTORC1 pathway (phosphorylation of Akt, 4EBP1, S6K1). Levels of Akt, 4EBP1 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 (p<0.0001). Levels of Akt, 4EBP1 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.