ReferenceID 4336
Decanoic acid inhibits mTORC1 activity independent of glucose and insulin signaling
Proc Natl Acad Sci U S A
Low-glucose and -insulin conditions, associated with ketogenic diets, can reduce the activity of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway, potentially leading to a range of positive medica
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Record Fields
Scalar fields from the final reference record.
- Reference Id
- 4336
- Evidence Id
- 20926
- Core Evidence Id
- 20926
- Source Reference Id
- 1940
- Herb2 Reference Id
- HBREF002737
- Subject Paper Key
- HBIN000930_32879008
- Pubmed Id
- 32879008
- Doi
- 10.1073/pnas.2008980117
- Paper Title
- Decanoic acid inhibits mTORC1 activity independent of glucose and insulin signaling
- Paper Abstract
- Low-glucose and -insulin conditions, associated with ketogenic diets, can reduce the activity of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway, potentially leading to a range of positive medical and health-related effects. Here, we determined whether mTORC1 signaling is also a target for decanoic acid, a key component of the medium-chain triglyceride (MCT) ketogenic diet. Using a tractable model system, Dictyostelium, we show that decanoic acid can decrease mTORC1 activity, under conditions of constant glucose and in the absence of insulin, measured by phosphorylation of eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1). We determine that this effect of decanoic acid is dependent on a ubiquitin regulatory X domain-containing protein, mediating inhibition of a conserved Dictyostelium AAA ATPase, p97, a homolog of the human transitional endoplasmic reticulum ATPase (VCP/p97) protein. We then demonstrate that decanoic acid decreases mTORC1 activity in the absence of insulin and under high-glucose conditions in ex vivo rat hippocampus and in tuberous sclerosis complex (TSC) patient-derived astrocytes. Our data therefore indicate that dietary decanoic acid may provide a new therapeutic approach to down-regulate mTORC1 signaling.
- Journal
- Proc Natl Acad Sci U S A
- Publish Year
- 2020
- Experiment Subject
- rat; human; patient
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Tuberous Sclerosis
- Paper Title Cn
- Paper Title En
- Decanoic acid inhibits mTORC1 activity independent of glucose and insulin signaling
- Bilingual Status
- semi_complete