In muscle cells, leucine does not consistently activate mTOR—a key protein for growth—when insulin is present, and the results vary between experiments, indicating it may not be a major target of leucine in this system.
Claim Context
In human skeletal muscle cells, leucine does not significantly alter phosphorylation of mTOR at Ser2448 under insulin stimulation, and results are inconsistent across biological replicates, suggesting mTOR may not be a primary target of leucine in this context.
“The pattern of pmTOR/mTOR, which is responsible for 4EBP1 and p70S6K phosphorylation, is more difficult to be deciphered given the high variability among the three replicates. Single time point comparisons do not allow to detect any significant difference after insulin stimulation, both alone and in combination with leucine, whereas the overall profile (Table 1) is not significantly expressed in any replicate during insulin stimulus, but indicates up-regulation in two out of three replicates under leucine + insulin stimulus.”
Evidence from Studies
No evidence studies found yet.
What Would Prove This
Per GRADE and EBM methodology, here is what ideal scientific evidence would look like to definitively prove or disprove this claim, ordered from strongest to weakest.
Whether leucine supplementation consistently activates mTOR at Ser2448 in human skeletal muscle during insulin stimulation across studies.
A systematic review and meta-analysis of all human studies measuring mTOR Ser2448 phosphorylation in muscle biopsies during insulin stimulation with and without leucine, using standardized Western blot protocols and time-course sampling.
Whether oral leucine ingestion enhances insulin-stimulated mTOR Ser2448 phosphorylation in human skeletal muscle.
A double-blind RCT with 40 healthy adults receiving 5g leucine or placebo before a hyperinsulinemic-euglycemic clamp, with muscle biopsies taken at 0, 15, 30, and 60 minutes to measure p-mTOR Ser2448 and Ser2481.
Whether habitual leucine intake correlates with basal or insulin-stimulated mTOR Ser2448 phosphorylation in muscle.
A prospective cohort of 200 adults with dietary leucine intake tracked over 6 months, with muscle biopsies taken at baseline and after a standardized meal to measure mTOR Ser2448 phosphorylation.
Whether plasma leucine levels correlate with muscle mTOR Ser2448 phosphorylation at rest.
A cross-sectional analysis of 180 adults measuring fasting plasma leucine and muscle p-mTOR Ser2448 levels via biopsy, adjusting for BMI, insulin sensitivity, and physical activity.
Whether a single individual's muscle mTOR Ser2448 phosphorylation responds to leucine during insulin stimulation.
A case report of one individual undergoing muscle biopsies during insulin clamps with and without leucine pre-incubation, measuring p-mTOR Ser2448 at multiple time points.