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

Author(s):  
Erwann Pain ◽  
Sonia Shinhmar ◽  
Robin S. B. Williams

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.

1993 ◽  
Vol 69 (2) ◽  
pp. 431-442 ◽  
Author(s):  
E. Guillot ◽  
P. Vaugelade ◽  
P. Lemarchali ◽  
A. Re Rat

In order to study the rate of intestinal absorption and hepatic uptake of medium-chain fatty acids (MCFA), six growing pigs, mean body weight 65 kg, were fitted with a permanent fistula in the duodenum and with three catheters in the portal vein, carotid artery and hepatic vein respectively. Two electromagnetic flow probes were also set up, one around the portal vein and one around the hepatic artery. A mixture of octanoic and decanoic acids, esterified as medium-chain triacylglycerols, together with maltose dextrine and a nitrogenous fraction was continuously infused for 1 h into the duodenum. Samples of blood were withdrawn from the three vessels at regular intervals for 12 h and further analysed for their non-esterified octanoic and decanoic acid contents. The concentration of non-esterified octanoic and decanoic acids in the portal blood rose sharply after the beginning of each infusion and showed a biphasic time-course with two maximum values, one after 15 min and a later one between 75 and 90 min. Only 65 % of octanoic acid infused into the duodenum and 54 % of decanoic acid were recovered in the portal flow throughout each experiment. The amounts of non-esterified MCFA taken up per h by the liver were close to those absorbed from the gut via the portal vein within the same periods of time, showing that the liver is the main site of utilization of MCFA in pigs. These results have been discussed with a special emphasis laid on the possible mechanisms of the biphasic time-course of MCFA absorption and the incomplete recovery in the portal blood of the infused fatty acids.


2020 ◽  
Author(s):  
Ada Admin ◽  
Anne-Marie Lundsgaard ◽  
Andreas M. Fritzen ◽  
Kim. A. Sjøberg ◽  
Maximilian Kleinert ◽  
...  

Medium-chain fatty acids (MCFAs) have in rodents been shown to have protective effects on glucose homeostasis during high-fat overfeeding. In this study, we investigated whether dietary MCFAs protect against insulin resistance induced by a hypercaloric high-fat diet in humans. Healthy, lean men ingested a eucaloric control diet and a three-day hypercaloric high-fat diet (+75% energy, 81-83E% fat) in randomized order. For one group (n=8), the high-fat diet was enriched with saturated long-chain FAs (LCSFA-HFD), while the other group (n=9) ingested a matched diet, but with ~30 g (5E%) saturated MCFAs (MCSFA-HFD) in substitution for a corresponding fraction of the saturated LCFAs. A hyperinsulinemic-euglycemic clamp with femoral arteriovenous balance and glucose tracer was applied after the control and hypercaloric diets. In LCSFA-HFD, whole body insulin sensitivity and peripheral insulin-stimulated glucose disposal were reduced. These impairments were prevented in MCSFA-HFD, accompanied by increased basal FA oxidation, maintained glucose metabolic flexibility, increased non-oxidative glucose disposal related to lower starting glycogen content and increased glycogen synthase activity, together with increased muscle lactate production. In conclusion, substitution of a small amount of dietary LCFAs with MCFAs rescues insulin action in conditions of lipid-induced energy excess.


2009 ◽  
Vol 25 (2) ◽  
pp. 185-194 ◽  
Author(s):  
Silvia Wein ◽  
Siegfried Wolffram ◽  
Jürgen Schrezenmeir ◽  
Daniela Gašperiková ◽  
Iwar Klimeš ◽  
...  

2021 ◽  
Vol 22 (12) ◽  
pp. 6453
Author(s):  
Qi Hui Sam ◽  
Hua Ling ◽  
Wen Shan Yew ◽  
Zhaohong Tan ◽  
Sharada Ravikumar ◽  
...  

Fatty acids are derived from diet and fermentative processes by the intestinal flora. Two to five carbon chain fatty acids, termed short chain fatty acids (SCFA) are increasingly recognized to play a role in intestinal homeostasis. However, the characteristics of slightly longer 6 to 10 carbon, medium chain fatty acids (MCFA), derived primarily from diet, are less understood. Here, we demonstrated that SCFA and MCFA have divergent immunomodulatory propensities. SCFA down-attenuated host pro-inflammatory IL-1β, IL-6, and TNFα response predominantly through the TLR4 pathway, whereas MCFA augmented inflammation through TLR2. Butyric (C4) and decanoic (C10) acid displayed most potent modulatory effects within the SCFA and MCFA, respectively. Reduction in TRAF3, IRF3 and TRAF6 expression were observed with butyric acid. Decanoic acid induced up-regulation of GPR84 and PPARγ and altered HIF-1α/HIF-2α ratio. These variant immune characteristics of the fatty acids which differ by just several carbon atoms may be attributable to their origins, with SCFA being primarily endogenous and playing a physiological role, and MCFA exogenously from the diet.


2021 ◽  
Author(s):  
Kalynne R Green ◽  
Kearney T. W. Gunsalus ◽  
Magdia De Jesus

The medium-chain fatty acids, octanoic and decanoic acid, found in coconut oil, were fungistatic and decanoic acid was fungicidal against a panel of Candida auris strains, during both planktonic and biofilm growth. The strains were from all four major geographic clades, and some were resistant to several classes of antifungal drugs. These compounds are safe, natural products and could provide a new strategy for skin decolonization and environmental decontamination.


2020 ◽  
Author(s):  
Ada Admin ◽  
Anne-Marie Lundsgaard ◽  
Andreas M. Fritzen ◽  
Kim. A. Sjøberg ◽  
Maximilian Kleinert ◽  
...  

Medium-chain fatty acids (MCFAs) have in rodents been shown to have protective effects on glucose homeostasis during high-fat overfeeding. In this study, we investigated whether dietary MCFAs protect against insulin resistance induced by a hypercaloric high-fat diet in humans. Healthy, lean men ingested a eucaloric control diet and a three-day hypercaloric high-fat diet (+75% energy, 81-83E% fat) in randomized order. For one group (n=8), the high-fat diet was enriched with saturated long-chain FAs (LCSFA-HFD), while the other group (n=9) ingested a matched diet, but with ~30 g (5E%) saturated MCFAs (MCSFA-HFD) in substitution for a corresponding fraction of the saturated LCFAs. A hyperinsulinemic-euglycemic clamp with femoral arteriovenous balance and glucose tracer was applied after the control and hypercaloric diets. In LCSFA-HFD, whole body insulin sensitivity and peripheral insulin-stimulated glucose disposal were reduced. These impairments were prevented in MCSFA-HFD, accompanied by increased basal FA oxidation, maintained glucose metabolic flexibility, increased non-oxidative glucose disposal related to lower starting glycogen content and increased glycogen synthase activity, together with increased muscle lactate production. In conclusion, substitution of a small amount of dietary LCFAs with MCFAs rescues insulin action in conditions of lipid-induced energy excess.


2017 ◽  
Vol 14 (3) ◽  
pp. 377-385 ◽  
Author(s):  
Angelica A. Ochoa-Flores ◽  
Josafat A. Hernández-Becerra ◽  
Adriana Cavazos-Garduño ◽  
Ida Soto-Rodríguez ◽  
Maria Guadalupe Sanchez-Otero ◽  
...  

Author(s):  
Huan Liu ◽  
Jingwei Huang ◽  
Hui Liu ◽  
Feng Li ◽  
Quansheng Peng ◽  
...  

Abstract Background The ketogenic diet (KD) can promote the anti-inflammatory metabolic state and increase ketone body level in rats. This study was to explore the effects and differences of KD with or without medium-chain fatty acids (MCFAs) on serum inflammatory factors and mTOR pathway in Sprague–Dawley (SD) rats. Results Male SD rats were assigned to five groups: control diet (C), 20% caloric restriction diet (LC), 20% caloric restriction ketogenic diet (containing MCFAs) (LCKD1), 20% caloric restriction ketogenic diet (LCKD2) and 20% caloric restriction foreign ketogenic diet (LCKD3), and fed for 30 d. LC and KD could significantly reduce the body weight of rats; LC and KD containing MCFAs showed anti-inflammatory effects; KD without MCFAs decreased the concentration of mTOR1, while KD containing MCFAs decreased the expression of AMPK, mtor1 and P70sk. Conclusions KD containing MCFAs showed better effects on the mTOR pathway and anti-inflammation than that without MCFAs.


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