scholarly journals Decanoic Acid Stimulates Autophagy in D. discoideum

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2946
Author(s):  
Eleanor C. Warren ◽  
Pavol Kramár ◽  
Katie Lloyd-Jones ◽  
Robin S. B. Williams
Keyword(s):  
Octanoic Acid ◽  
Medium Chain Triglyceride ◽  
Decanoic Acid ◽  
Autophagic Flux ◽  
Therapeutic Effects ◽  
Autophagosome Formation ◽  
Control Activity ◽  
Medium Chain ◽  
Ketogenic Diets ◽  
Autophagy Induction

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.

scholarly journals Neuronal decanoic acid oxidation is markedly lower than that of octanoic acid: A mechanistic insight into the medium-chain triglyceride ketogenic diet

Epilepsia ◽  
2017 ◽  
Vol 58 (8) ◽  
pp. 1423-1429 ◽  
Author(s):  
Aziza Khabbush ◽  
Michael Orford ◽  
Yi-Chen Tsai ◽  
Tricia Rutherford ◽  
Maura O'Donnell ◽  
...  
Keyword(s):  
Ketogenic Diet ◽  
Octanoic Acid ◽  
Medium Chain Triglyceride ◽  
Decanoic Acid ◽  
Acid Oxidation ◽  
Medium Chain ◽  
Mechanistic Insight ◽  
Insight Into

scholarly journals Using Dictyostelium to Advance Our Understanding of the Role of Medium Chain Fatty Acids in Health and Disease

2021 ◽  
Vol 9 ◽  
Author(s):  
Erwann Pain ◽  
Sonia Shinhmar ◽  
Robin S. B. Williams
Keyword(s):  
Fatty Acids ◽  
Molecular Mechanisms ◽  
Medium Chain Triglyceride ◽  
Decanoic Acid ◽  
High Fat ◽  
Medium Chain ◽  
Medium Chain Fatty Acids ◽  
Ketogenic Diets ◽  
Health And Disease ◽  
Chain Fatty Acids

Ketogenic diets have been utilized for many years to improve health, and as a dietary approach for the treatment of a range of diseases, where the mechanism of these low carbohydrate and high fat diets is widely considered to be through the production of metabolic products of fat breakdown, called ketones. One of these diets, the medium chain triglyceride ketogenic diet, involves high fat dietary intake in the form of medium chain fatty acids (MCFAs), decanoic and octanoic acid, and is commonly used in endurance and high intensity exercises but has also demonstrated beneficial effects in the treatment of numerous pathologies including drug resistant epilepsy, cancer, and diabetes. Recent advances, using Dictyostelium discoideum as a model, have controversially proposed several direct molecular mechanisms for decanoic acid in this diet, independent of ketone generation. Studies in this model have identified that decanoic acid reduces phosphoinositide turnover, diacylglycerol kinase (DGK) activity, and also inhibits the mechanistic target of rapamycin complex 1 (mTORC1). These discoveries could potentially impact the treatment of a range of disorders including epilepsy, cancer and bipolar disorder. In this review, we summarize the newly proposed mechanisms for decanoic acid, identified using D. discoideum, and highlight potential roles in health and disease treatment.

scholarly journals Octanoic acid a major component of widely consumed medium-chain triglyceride ketogenic diet is detrimental to bone

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shreshta Jain ◽  
Reena Rai ◽  
Divya Singh ◽  
Divya Vohora
Keyword(s):  
Bone Loss ◽  
Ketogenic Diet ◽  
Octanoic Acid ◽  
Bone Microarchitecture ◽  
Medium Chain Triglyceride ◽  
Decanoic Acid ◽  
Clinical Findings ◽  
Micro Computed Tomography ◽  
Negative Effects ◽  
Treatment Groups

AbstractOctanoic acid is a medium-chained saturated fatty acid found abundantly in the ketogenic dietary supplements containing medium chained triglycerides (MCT) along with decanoic acid. The MCT ketogenic diet is commonly consumed for weight loss but has also showcased neuroprotective potential against neurodegenerative disorders. However, recent clinical findings have reported a critical disadvantage with the long-term consumption of ketogenic diet i.e. bone loss. The following study was employed to investigate whether the two major components of MCT diet also possess bone loss potential as observed with classical ketogenic diet. Swiss albino mice aged between 10 and 12 weeks, were divided into 3 treatment groups that were administered with oral suspensions of octanoic acid, decanoic acid and a combination of both for 4 weeks. Bone specific markers, microarchitectural parameters, using micro computed tomography, and biomechanical strength were analyzed. Remarkably deleterious alterations in the trabecular bone microarchitecture, and on bone markers were observed in the octanoic acid treated groups. Our results suggest significant negative effects on bone health by octanoic acid. These findings require further investigation and validation in order to provide significant clinically relevant data to possibly modify dietary composition of the MCT ketogenic diet.

scholarly journals The retrospective research of enteral nutrition with medium-chain triglyceride and total parenteral nutrition support of postoperative chylothorax in adults

2020 ◽  
Vol 8 ◽  
pp. 205031212093822
Author(s):  
Jie Zheng ◽  
Ying-Yi Chen ◽  
Chun-Ying Zhang ◽  
Wen-Qian Zhang ◽  
Zhi-Yong Rao
Keyword(s):  
Enteral Nutrition ◽  
Parenteral Nutrition ◽  
Total Parenteral Nutrition ◽  
Heart Surgery ◽  
Medium Chain Triglyceride ◽  
Nutrition Support ◽  
Therapeutic Effects ◽  
Medium Chain ◽  
First Choice ◽  
Support Cost

Background: Chylothorax is caused by thoracic lymphatic system injuries that leads to the lymph extravasating into the thoracic cavity. There are few reports comparing the therapeutic effects of enteral nutrition with medium-chain triglyceride and total parenteral nutrition, and the results are inconsistent. Our study aimed to research the optimum nutrition support method for chylothorax. Study design: We retrospectively reviewed 35 chylothorax patients after heart and chest surgery from 2014 to 2018, at West China Hospital of Sichuan University, among them there were 27 post-heart surgery patients. We analyzed the therapeutic effects and costs of enteral nutrition with medium-chain triglyceride (E group) and total parenteral nutrition (T group) for chylothorax. Results: The results were similar in patients with all surgeries and patients with only post heart surgery. The total cost during hospitalization in E group was higher than T group ( P < 0.01), whereas the nutrition support cost was lower ( P < 0.001). The length of hospital stay was longer in E group than T group ( P > 0.05). Time from admission to surgery was shorter and from surgery to chylothorax diagnosis was longer in E group compared with T group. Time to resolution and removal of drainage was shorter in E group than T group but the differences were not significant. Conclusion: The therapeutic effects in enteral nutrition with medium-chain triglyceride and total parenteral nutrition had no obvious differences. Moreover, enteral nutrition with medium-chain triglyceride is safer and more economical. Therefore, we suggest that enteral nutrition with medium-chain triglyceride could be the first choice to treat postoperative chylothorax when the gastrointestinal tract function is allowed, and this result could be considered for postoperative chylous ascites.

Growth of Children on Classical and Medium-Chain Triglyceride Ketogenic Diets

PEDIATRICS ◽  
2008 ◽  
Vol 122 (2) ◽  
pp. e334-e340 ◽  
Author(s):  
E. G. Neal ◽  
H. M. Chaffe ◽  
N. Edwards ◽  
M. S. Lawson ◽  
R. H. Schwartz ◽  
...  
Keyword(s):  
Medium Chain Triglyceride ◽  
Medium Chain ◽  
Ketogenic Diets

scholarly journals Optimizing a Fed-Batch High-Density Fermentation Process for Medium Chain-Length Poly(3-Hydroxyalkanoates) in Escherichia coli

2021 ◽  
Vol 9 ◽  
Author(s):  
Ryan A. Scheel ◽  
Truong Ho ◽  
Yuki Kageyama ◽  
Jessica Masisak ◽  
Seamus McKenney ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Fatty Acid ◽  
Chain Length ◽  
Fermentation Process ◽  
Octanoic Acid ◽  
Decanoic Acid ◽  
High Density ◽  
Fed Batch ◽  
Medium Chain ◽  
Medium Chain Length

Production of medium chain-length poly(3-hydroxyalkanoates) [PHA] polymers with tightly defined compositions is an important area of research to expand the application and improve the properties of these promising biobased and biodegradable materials. PHA polymers with homopolymeric or defined compositions exhibit attractive material properties such as increased flexibility and elasticity relative to poly(3-hydroxybutyrate) [PHB]; however, these polymers are difficult to biosynthesize in native PHA-producing organisms, and there is a paucity of research toward developing high-density cultivation methods while retaining compositional control. In this study, we developed and optimized a fed-batch fermentation process in a stirred tank reactor, beginning with the biosynthesis of poly(3-hydroxydecanoate) [PHD] from decanoic acid by β-oxidation deficient recombinant Escherichia coli LSBJ using glucose as a co-substrate solely for growth. Bacteria were cultured in two stages, a biomass accumulation stage (37°C, pH 7.0) with glucose as the primary carbon source and a PHA biosynthesis stage (30°C, pH 8.0) with co-feeding of glucose and a fatty acid. Through iterative optimizations of semi-defined media composition and glucose feed rate, 6.0 g of decanoic acid was converted to PHD with an 87.5% molar yield (4.54 g L–1). Stepwise increases in the amount of decanoic acid fed during the fermentation correlated with an increase in PHD, resulting in a final decanoic acid feed of 25 g converted to PHD at a yield of 89.4% (20.1 g L–1, 0.42 g L–1 h–1), at which point foaming became uncontrollable. Hexanoic acid, octanoic acid, 10-undecenoic acid, and 10-bromodecanoic acid were all individually supplemented at 20 g each and successfully polymerized with yields ranging from 66.8 to 99.0% (9.24 to 18.2 g L–1). Using this bioreactor strategy, co-fatty acid feeds of octanoic acid/decanoic acid and octanoic acid/10-azidodecanoic acid (8:2 mol ratio each) resulted in the production of their respective copolymers at nearly the same ratio and at high yield, demonstrating that these methods can be used to control PHA copolymer composition.

DEODORIZING MORINDA CITRIFOLIA (MENGKUDU) STRONG ODOR JUICE BY β-CYCLODEXTRIN-ORGANIC ACIDS INCLUSION

2016 ◽  
Vol 78 (10) ◽  
Author(s):  
Yeap Shong Yien ◽  
Osman Hassan ◽  
Saiful Irwan Zubairi
Keyword(s):  
Fatty Acids ◽  
Melting Point ◽  
Inclusion Complex ◽  
Octanoic Acid ◽  
Dry Weight ◽  
Decanoic Acid ◽  
Hexanoic Acid ◽  
Morinda Citrifolia ◽  
Therapeutic Effects ◽  
Clinical Practices

Morinda citrifolia (noni) which is locally known as mengkudu in Malaysia, is a small evergreen tree usually found growing in open coastal regions at sea level and in forest areas. It has been reported to have  various therapeutic effects, including having anticancer activities, in clinical practices and laboratory animal models. However, consumers mostly avoid consuming mengkudu products due to  mengkudu’s sensory properties such as a strong rancid-like odor that is released when the mengkudu fruit is fully ripe. Therefore, this study was  conducted to determine the effectiveness of β-cyclodextrin in deodorizing the unpleasant odors in mengkudu juice which are mainly caused by medium chain fatty acids such as hexanoic acid, octanoic acid and decanoic acid. Initially, the optimal molar ratio for the encapsulation of hexanoic, octanoic and decanoic acid by β-cyclodextrin was constructed as a model system prior to the encapsulation of the juice. The formation of inclusion complex between all acids and β-cyclodextrin was verified by means of differential scanning calorimetry (DSC). Next, four dry weight ratios of mengkudu juice to β–cyclodextrin (1:0.5, 1:1, 1:1.5 and 1:2) were selected to determine the degree of the effectiveness of β-cyclodextrin in encapsulating unpleasant odors via gas chromatography-mass spectrometry (GC-MS). Based on the results, inclusion complex formation was confirmed by DSC through the disappearance of a melting point for pure acid, and shifting to a lower melting point from the pure β–cyclodextrin after the encapsulation process. Moreover, there were significant differences observed between hexanoic acid and octanoic acid content in the mengkudu juice before and after adding β-cyclodextrin (p<0.05). On the other hand, the results obtained from GC-MS and sensory evaluation had contributed to an optimum entrapment of fatty acids at the optimal dry weight ratio of 1:0.5 (dry weight of mengkudu: β-cyclodextrin). Hence, the ability of β-cyclodextrin as a masking agent has been proven to be able to reduce the odor-based fatty acids in mengkudu juice.

Identifying the Molecular Mechanism of the Medium Chain Triglyceride (Ketogenic) Diet

2016 ◽  
Author(s):  
Matthew C. Walker ◽  
Robin S.B. Williams
Keyword(s):  
Ketogenic Diet ◽  
Seizure Control ◽  
Medium Chain Triglyceride ◽  
Decanoic Acid ◽  
In Vivo Models ◽  
Principal Mechanism ◽  
Excitatory Neurotransmitter ◽  
Medium Chain

The medium chain triglyceride (MCT) ketogenic diet provides a highly effective and commonly used approach for treating drug-resistant epilepsy. It is associated with elevated levels of two MCT-derived fatty acids, decanoioc and octanoic acids. Researchers have identified a role for decanoic acid and a range of novel related chemicals in seizure control in multiple acute in vitro and in vivo models. A principal mechanism of decanoic acid is direct inhibition of AMPA receptors, key excitatory neurotransmitter receptors widely recognized as a target for seizure control. These data suggest a therapeutic mechanism of the MCT ketogenic diet through a direct fatty acid–dependent mechanism, independent of ketosis. This discovery will enable the development of an improved and, potentially, better-tolerated diet and the generation of a corresponding pharmaceutical approach. The diet should be termed the MCT diet, as the consequent ketosis may not be necessary for seizure control.

(omega-1)-Hydroxymonocarboxylic acids in urine of infants fed medium-chain triglycerides.

1981 ◽  
Vol 27 (10) ◽  
pp. 1661-1664 ◽  
Author(s):  
Y Shigematsu ◽  
T Momoi ◽  
M Sudo ◽  
Y Suzuki
Keyword(s):  
Mass Spectrometry ◽  
Fatty Acids ◽  
Octanoic Acid ◽  
Monocarboxylic Acid ◽  
Decanoic Acid ◽  
Gas Chromatography Mass Spectrometry ◽  
Medium Chain Triglycerides ◽  
Medium Chain ◽  
Chain Acyl ◽  
Total Fatty Acids

Abstract Organic acids in the urine of infants fed a formula containing medium-chain triglycerides (octanoic acid 49% and decanoic acid 26% of total fatty acids) were determined by gas chromatography-mass spectrometry. We found a considerable amount of 5-hydroxyhexanoic acid and 7-hydroxyoctanoic acid, but no detectable 9-hydroxydecanoic acid, as well as a large amount of C6-C10-dicarboxylic acid. We believe that such acids are derived, via (omega-1)-hydroxylation, from medium-chain monocarboxylic acid or medium-chain acyl-CoA in the liver cell. The degree of (omega-1)-hydroxylation of medium-chain fatty acids relative to omega-hydroxylation apparently increases as the chain length of the fatty acids decreases.

scholarly journals The Effects of a Ketogenic Medium-Chain Triglyceride Diet on the Feces in Dogs With Idiopathic Epilepsy

2020 ◽  
Vol 7 ◽  
Author(s):  
Rachel Pilla ◽  
Tsz Hong Law ◽  
Yuanlong Pan ◽  
Brian M. Zanghi ◽  
Qinghong Li ◽  
...  
Keyword(s):  
Neuroprotective Effect ◽  
Medium Chain Triglyceride ◽  
Idiopathic Epilepsy ◽  
Rrna Gene ◽  
Fecal Microbiome ◽  
Medium Chain ◽  
Ketogenic Diets ◽  
Potential Biomarker ◽  
Α Diversity ◽  
And Behavior

Consumption of diets containing medium chain triglycerides have been shown to confer neuroprotective and behavior modulating effects. We aimed to identify metabolic and microbiome perturbations in feces that are associated with consumption of a medium chain triglyceride ketogenic diet (MCT-KD) in dogs with idiopathic epilepsy. We used 16S rRNA gene sequencing to generate microbiome profiles and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) to generate lipidomic profiles of canine feces. We made comparisons between the MCT-KD, standardized placebo diet and baseline pre-trial diet phases. Consumption of the MCT-KD resulted in a significant increase in the species richness (α-diversity) of bacterial communities found in the feces when compared to the baseline diet. However, phylogenetical diversity between samples (beta-diversity) was not affected by diet. An unnamed Bacteroidaceae species within genus 5-7N15 was identified by LEfSe as a potential biomarker associated with consumption of the MCT-KD, showing an increased abundance (p = 0.005, q = 0.230) during consumption of MCT-KD. In addition, unclassified members of families Erysipelotrichaceae (p = 0.013, q = 0.335) and Fusobacteriaceae (p = 0.022, q = 0.358) were significantly increased during MCT-KD consumption compared to baseline. Blautia sp. and Megamonas sp. instead were decreased during consumption of either placebo or MCT-KD (p = 0.045, q = 0.449, and p = 0.039, q = 0.449, respectively). Bacteroidaceae, including genus 5-7N15, have previously been associated with non-aggressive behavior in dogs. In addition, 5-7N15 is correlated in humans with Akkermansia, a genus known to be involved in the neuroprotective effect of ketogenic diets in mice models of seizures. Five metabolite features, tentatively identified as long chain triglycerides, were significantly higher after consumption of the placebo diet, but no unique features were identified after consumption of the MCT-KD. The data presented in this study highlight significant changes shown in both the fecal microbiome and lipidome as a result of consumption of the MCT-KD. Elucidating the global canine gut response to MCT consumption will improve our understanding of the potential mechanisms which confer anti-seizure and behavior modulating effects. Further studies should aim to characterize the gut microbiome of both dogs with epilepsy and healthy controls.

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