Decanoic Acid Stimulates Autophagy in D. discoideum

Abstract

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 Dictyostelium, 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.

Neuroprotective effects of a medium chain fatty acid, decanoic acid, isolated from H. leucospilota against Parkinsonism in C. elegans PD model

“…These lines of evidence support our hypothesis that decanoic acid isolated from H. leucospilota alleviates 6-OHDA toxicities by upregulating antioxidative defense in C. elegans PD model. Moreover, previous study reported that decanoic acid activates autophagy by upregulating autophagy-inducing protein including Atg1 and Atg8 ( Warren et al, 2021 ). Autophagy is the major clearance system of α-synuclein aggregation ( Maiti et al, 2017 ).…”

Stability of the Inclusion Complexes of Dodecanoic Acid with α-Cyclodextrin, β-Cyclodextrin and 2-HP-β-Cyclodextrin

“…Lauric acid also has antiviral properties. Monolaurin is effective against lipid membrane viruses (such as HIV-1, measles, sarcoma and vesicular stomatitis) [ 14 , 15 , 16 ].…”