Decanoic Acid Stimulates Autophagy in <i>D. discoideum</i>

Ketogenic diets, used in epilepsy treatment, are considered to work through reduced glucose and ketone generation to regulate a range of cellular process including autophagy induction. Recent studies into the medium-chain triglyceride (MCT) ketogenic diet have suggested that medium-chain fatty acids...

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Autores principales:	Eleanor C. Warren, Pavol Kramár, Katie Lloyd-Jones, Robin S. B. Williams
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	autophagy cancer decanoic acid <i>Dictyostelium</i> epilepsy 4BCCA Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/ca710e6fc0944923bb997b5e0eb21466
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spelling	oai:doaj.org-article:ca710e6fc0944923bb997b5e0eb214662021-11-25T17:09:38ZDecanoic Acid Stimulates Autophagy in <i>D. discoideum</i>10.3390/cells101129462073-4409https://doaj.org/article/ca710e6fc0944923bb997b5e0eb214662021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/2946https://doaj.org/toc/2073-4409Ketogenic diets, used in epilepsy treatment, are considered to work through reduced glucose and ketone generation to regulate a range of cellular process including autophagy induction. Recent studies into the medium-chain triglyceride (MCT) ketogenic diet have suggested that medium-chain fatty acids (MCFAs) provided in the diet, decanoic acid and octanoic acid, cause specific therapeutic effects independent of glucose reduction, although a role in autophagy has not been investigated. Both autophagy and MCFAs have been widely studied in <i>Dictyostelium</i>, with findings providing important advances in the study of autophagy-related pathologies such as neurodegenerative diseases. Here, we utilize this model to analyze a role for MCFAs in regulating autophagy. We show that treatment with decanoic acid but not octanoic acid induces autophagosome formation and modulates autophagic flux in high glucose conditions. To investigate this effect, decanoic acid, but not octanoic acid, was found to induce the expression of autophagy-inducing proteins (Atg1 and Atg8), providing a mechanism for this effect. Finally, we demonstrate a range of related fatty acid derivatives with seizure control activity, 4BCCA, 4EOA, and Epilim (valproic acid), also function to induce autophagosome formation in this model. Thus, our data suggest that decanoic acid and related compounds may provide a less-restrictive therapeutic approach to activate autophagy.Eleanor C. WarrenPavol KramárKatie Lloyd-JonesRobin S. B. WilliamsMDPI AGarticleautophagycancerdecanoic acid<i>Dictyostelium</i>epilepsy4BCCABiology (General)QH301-705.5ENCells, Vol 10, Iss 2946, p 2946 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	autophagy cancer decanoic acid <i>Dictyostelium</i> epilepsy 4BCCA Biology (General) QH301-705.5
spellingShingle	autophagy cancer decanoic acid <i>Dictyostelium</i> epilepsy 4BCCA Biology (General) QH301-705.5 Eleanor C. Warren Pavol Kramár Katie Lloyd-Jones Robin S. B. Williams Decanoic Acid Stimulates Autophagy in <i>D. discoideum</i>
description	Ketogenic diets, used in epilepsy treatment, are considered to work through reduced glucose and ketone generation to regulate a range of cellular process including autophagy induction. Recent studies into the medium-chain triglyceride (MCT) ketogenic diet have suggested that medium-chain fatty acids (MCFAs) provided in the diet, decanoic acid and octanoic acid, cause specific therapeutic effects independent of glucose reduction, although a role in autophagy has not been investigated. Both autophagy and MCFAs have been widely studied in <i>Dictyostelium</i>, with findings providing important advances in the study of autophagy-related pathologies such as neurodegenerative diseases. Here, we utilize this model to analyze a role for MCFAs in regulating autophagy. We show that treatment with decanoic acid but not octanoic acid induces autophagosome formation and modulates autophagic flux in high glucose conditions. To investigate this effect, decanoic acid, but not octanoic acid, was found to induce the expression of autophagy-inducing proteins (Atg1 and Atg8), providing a mechanism for this effect. Finally, we demonstrate a range of related fatty acid derivatives with seizure control activity, 4BCCA, 4EOA, and Epilim (valproic acid), also function to induce autophagosome formation in this model. Thus, our data suggest that decanoic acid and related compounds may provide a less-restrictive therapeutic approach to activate autophagy.
format	article
author	Eleanor C. Warren Pavol Kramár Katie Lloyd-Jones Robin S. B. Williams
author_facet	Eleanor C. Warren Pavol Kramár Katie Lloyd-Jones Robin S. B. Williams
author_sort	Eleanor C. Warren
title	Decanoic Acid Stimulates Autophagy in <i>D. discoideum</i>
title_short	Decanoic Acid Stimulates Autophagy in <i>D. discoideum</i>
title_full	Decanoic Acid Stimulates Autophagy in <i>D. discoideum</i>
title_fullStr	Decanoic Acid Stimulates Autophagy in <i>D. discoideum</i>
title_full_unstemmed	Decanoic Acid Stimulates Autophagy in <i>D. discoideum</i>
title_sort	decanoic acid stimulates autophagy in <i>d. discoideum</i>
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/ca710e6fc0944923bb997b5e0eb21466
work_keys_str_mv	AT eleanorcwarren decanoicacidstimulatesautophagyiniddiscoideumi AT pavolkramar decanoicacidstimulatesautophagyiniddiscoideumi AT katielloydjones decanoicacidstimulatesautophagyiniddiscoideumi AT robinsbwilliams decanoicacidstimulatesautophagyiniddiscoideumi
_version_	1718412678858276864

Decanoic Acid Stimulates Autophagy in <i>D. discoideum</i>

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