Evidence for a role for Sestrin1 in mediating leucine-induced activation of mTORC1 in skeletal muscle.
Level 5 - mechanism / opinion, no new human data
Preclinical laboratory and in vivo mechanistic study without human clinical data.
PubMed 30835510 · doi:10.1152/ajpendo.00522.2018
What was done
Researchers measured the relative tissue expression profiles of Sestrin1, Sestrin2, and Sestrin3, and calculated their dissociation constants for leucine by assessing leucine-induced dissociation of the Sestrin-GATOR2 complex in cell culture. They also evaluated the disassembly of specific Sestrin-GATOR2 complexes in vivo following oral leucine administration.
What was found
The abstract reports no numerical values. Sestrin expression varied substantially across tissues; in skeletal muscle, Sestrin1 expression was higher than Sestrin3, while Sestrin2 was markedly lower. Sestrin1 demonstrated the highest affinity for leucine, and Sestrin3 had the lowest affinity. Oral leucine administration stimulated the disassembly of the Sestrin1-GATOR2 complex, but not the Sestrin2- or Sestrin3-GATOR2 complexes.
Why it matters
These findings clarify the specific molecular sensor responsible for leucine-mediated mTORC1 signaling in skeletal muscle, highlighting Sestrin1 rather than Sestrin2 as the primary physiologic mediator.
Limits
The abstract contains no quantitative metrics, confidence intervals, sample sizes, or animal model details. Direct clinical translation to human skeletal muscle protein synthesis requires validation in human trials.
Cited by
- context mTORC1 in muscle tissue has a significantly higher affinity for leucine than mTORC1 in adipose tissue or hepatocytes.