Decanoic acid inhibits mTORC1 activity independent of glucose and insulin signaling
Eleanor C. Warren, Stephanie Dooves, Eleonora Lugarà, Joseph Damstra‐Oddy, Judith Schaf, Vivi M. Heine, Matthew C. Walker, Robin S. B. Williams
Abstract
Significance The mTORC1 complex provides a critical role in cell function, regulating a variety of processes including growth and autophagy. mTORC1 signaling is hyperactivated in a range of common diseases including cancer, epilepsy, and neurodegenerative disorders. Hence, mTORC1 signaling provides an important target for regulation in many contexts. Here, we show that decanoic acid, a key component of a widely used medicinal diet, reduces mTORC1 activity. We identify this in a tractable model system, and validate it in ex vivo rat brain tissue and in human iPSC-derived astrocytes from patients with a clinically relevant disease. Thus, we provide insight into an easily accessible therapeutic approach for a range of diseases.