dictyNews

Electronic Edition

Volume 46, number 24

September 4, 2020



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Abstracts

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Decanoic acid inhibits mTORC1 activity independent of glucose and 

insulin signalling



Eleanor C Warren1, Stephanie Dooves2, Eleonora Lugarà3, Joseph 

Damstra-Oddy1, Judith Schaf1, Vivi M Heine2,4, Mathew C Walker3, 

Robin SB Williams1*



1Centre for Biomedical Sciences, Department of Biological Sciences, 

Royal Holloway University of London, Egham, United Kingdom

2Department of Child & Youth Psychiatry, Amsterdam UMC, 

Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam 

1081 HV, The Netherlands.

3Department of Clinical and Experimental Epilepsy, Queen Square 

Institute of Neurology, University College London, London, 

United Kingdom

4Department of Complex Trait Genetics, Centre for Neurogenomics 

and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit 

Amsterdam, Amsterdam 1081 HV, the Netherlands.





Proceedings of the National Academy of Science (PNAS), In press

https://www.pnas.org/content/early/2020/09/01/2008980117



Low glucose and insulin conditions, associated with ketogenic diets, 

can reduce the activity of the mechanistic target of rapamycin 

complex 1 (mTORC1) signalling pathway, potentially leading to a 

range of positive medical and health-related effects. Here, we 

determined whether mTORC1 signalling 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), through a ubiquitin regulatory X 

domain-containing protein to inhibit the activity of a conserved 

Dictyostelium AAA ATPase, p97, similar to human transitional 

endoplasmic reticulum ATPase (VCP/p97) activity. 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 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 

signalling.





submitted by: Robin Williams [[log in to unmask]]

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[End dictyNews, volume 46, number 24]