Medium-chain triglycerides inhibit long-chain triglyceride-induced GIP secretion through GPR120-dependent inhibition of CCK.
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ABSTRACT:
SUBMITTER: Murata Y
PROVIDER: S-EPMC8382997 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Ketones provide an alternative brain fuel and may be neuroprotective in older people. Little is known of how to optimize the ketogenic effect of C8:0-C10:0 medium chain triglyceride supplement (kMCT). Metabolic switching (MS) from glucose to ketones as a fuel may have metabolic benefits but has not been extensively studied in humans. The objective of the present study was to use an 8 h metabolic study day protocol to assess the influence of typical components of MS, including a kMCT supplement, low-carbohydrate meal and meal timing, on blood ketones, glucose, insulin and free fatty acids (FFA). In one test, the effect of age was also investigated. Over the 8 h metabolic study day, two 10 g doses of the kMCT increased the plasma ketone response by 19% while reducing overall glycemia by 12% without altering insulin or FFA levels. Moreover, a single early meal (breakfast but no lunch) potentiated the ketogenic effect of MS over 8 h, compared to a single delayed meal (lunch but no breakfast). Age and the low carbohydrate meal did not affect the ketones response. We conclude that an 8-h test period can be used to assess metabolic changes during short-term MS. kMCT provide a robust short-term increase in ketones and might enhance the metabolic effectiveness of short-term or intermittent fasting as a component of MS.
| S-EPMC7005013 | biostudies-literature
Project description:BACKGROUND:Candida is an important cause of infections in premature infants. Gastrointestinal colonization with Candida is a common site of entry for disseminated disease. The objective of this study was to determine whether a dietary supplement of medium-chain triglycerides (MCTs) reduces Candida colonization in preterm infants. METHODS:Preterm infants with Candida colonization (n = 12) receiving enteral feedings of either infant formula (n = 5) or breast milk (n = 7) were randomized to MCT supplementation (n = 8) or no supplementation (n = 4). Daily stool samples were collected to determine fungal burden during a 3-week study period. Infants in the MCT group received supplementation during 1 week of the study period. The primary outcome was fungal burden during the supplementation period as compared with the periods before and after supplementation. RESULTS:Supplementation of MCT led to a marked increase in MCT intake relative to unsupplemented breast milk or formula as measured by capric acid content. In the treatment group, there was a significant reduction in fungal burden during the supplementation period as compared with the period before supplementation (rate ratio, 0.15; P = 0.02), with a significant increase after supplementation was stopped (rate ratio, 61; P < 0.001). Fungal burden in the control group did not show similar changes. CONCLUSIONS:Dietary supplementation with MCT may be an effective method to reduce Candida colonization in preterm infants.
| S-EPMC6604858 | biostudies-literature
Project description:Medium Chain Triglycerides (MCT) is a dietary supplement and usually used along with medications for treating food absorption disorders including diarrhea, steatorrhea and liver disease. It has been shown that MCT plays a role in lowering weight, and decreasing metabolic syndrome, abdominal obesity and inflammation. However, it is still unknown whether MCT enhances exercise endurance. Here, we demonstrated that MCT containing diet improves high temperature induced exercise performance impairment. We found that MCT up-regulates the expression and protein levels of genes involved in mitochondrial biogenesis and metabolism. Further investigation demonstrated that the increased mitochondrial biogenesis and metabolism is mediated through the activation of Akt and AMPK signaling pathways and inhibition of TGF-β signaling pathway. Collectively, our findings indicate a beneficial effect of dietary MCT in exercise performance through the increase of mitochondrial biogenesis and metabolism.
| S-EPMC5805166 | biostudies-literature
Project description:The triglyceride of heptanoate (C7 fatty acid), triheptanoin, is a tasteless oil used to treat rare metabolic disorders in USA and France. Heptanoate is metabolized by β-oxidation to provide propionyl-CoA, which after carboxylation can produce succinyl-CoA, resulting in anaplerosis - the refilling of the tricarboxylic acid cycle. Heptanoate is also metabolized by the liver to the C5 ketones, β-ketopentanoate and/or β-hydroxypentanoate, which are released into the blood and thought to enter the brain via monocarboxylate transporters. Oral triheptanoin has recently been discovered to be reproducibly anticonvulsant in acute and chronic mouse seizures models. However, current knowledge on alterations of brain metabolism after triheptanoin administration and anaplerosis via propionyl-CoA carboxylation in the brain is limited. This review outlines triheptanoin's unique anticonvulsant profile and its clinical potential for the treatment of medically refractory epilepsy. Anaplerosis as a therapeutic approach for the treatment of epilepsy is discussed. More research is needed to elucidate the anticonvulsant mechanism of triheptanoin and to reveal its clinical potential for the treatment of epilepsy and other disorders of the brain.
| S-EPMC3422680 | biostudies-literature
Project description:Medium chain triglycerides (MCTs) are used to treat neurologic disorders with metabolic impairments, including childhood epilepsy and early Alzheimer's disease. However, the metabolic effects of MCTs in the brain are still unclear. Here, we studied the effects of feeding even and uneven MCTs on brain glucose metabolism in the mouse. Adult mice were fed 35% (calories) of trioctanoin or triheptanoin (the triglycerides of octanoate or heptanoate, respectively) or a matching control diet for 3 weeks. Enzymatic assays and targeted metabolomics by liquid chromatography tandem mass spectrometry were used to quantify metabolites in extracts from the hippocampal formations (HFs). Both oils increased the levels of β-hydroxybutyrate, but no other significant metabolic alterations were observed after triheptanoin feeding. The levels of glucose 6-phosphate and fructose 6-phosphate were increased in the HF of mice fed trioctanoin, whereas levels of metabolites further downstream in the glycolytic pathway and the pentose phosphate pathway were reduced. This indicates that trioctanoin reduces glucose utilization because of a decrease in phosphofructokinase activity. Trioctanoin and triheptanoin showed similar anticonvulsant effects in the 6 Hz seizure model, but it remains unknown to what extent the anticonvulsant mechanism(s) are shared. In conclusion, triheptanoin unlike trioctanoin appears to not alter glucose metabolism in the healthy brain.
| S-EPMC3887358 | biostudies-other
Project description:Consuming medium-chain triglycerides (MCT) may reduce subsequent energy intake and increase satiety compared to long-chain triglycerides (LCT) but this may be dependent on the physical form in which MCT is ingested. Twenty-nine participants completed four trials where they consumed a breakfast containing either LCT or MCT in solid (Con-S and MCT-S, respectively) or liquid (Con-L and MCT-L, respectively) form. Appetite ratings and gastric emptying (GE) were taken at baseline and at 15 min intervals for 4 h. Energy intake was assessed at an ad libitum meal and via weighed food records for the remainder of the day. Ad libitum energy intake was highest in Con-L (4101 ± 1278 kJ vs. Con-S, 3323 ± 1196; MCT-S, 3516 ± 1058; MCT-L, 3257 ± 1345; p = 0.001). Intake over the whole day was significantly lower in MCT-L (7904 ± 3244) compared to Con-L (9531 ± 3557; p = 0.001). There were significant differences in GE times (p < 0.05), with MCT breakfasts delaying GE to a greater extent than LCT, and MCT-L having the longest GE times. There were no differences in appetite sensations. MCT reduce subsequent intake without affecting subjective sensations of appetite when consumed in liquid form.
| S-EPMC6683029 | biostudies-literature
Project description:ObjectiveTo investigate the feasibility, safety, and tolerability of add-on treatment of the triglycerides of heptanoate (triheptanoin) vs the triglycerides of octanoate and decanoate (medium chain triglycerides [MCTs]) in adults with treatment-refractory epilepsy.MethodsAfter an 8-week prospective baseline period, people with drug-resistant epilepsy were randomized in a double-blind fashion to receive triheptanoin or MCTs. Treatment was titrated over 3 weeks to a maximum of 100 mL/d to be distributed over 3 meals and mixed into food, followed by 12-week maintenance before tapering. The primary aims were to assess the following: (a) safety by comparing the number of intervention-related adverse events with triheptanoin vs MCT treatment and (b) adherence, measured as a percentage of the prescribed treatment doses taken.ResultsThirty-four people were randomized (17 to MCT and 17 to triheptanoin). There were no differences regarding (a) the number of participants completing the study (11 vs 9 participants), (b) the time until withdrawal, (c) the total number of adverse events or those potentially related to treatment, (d) median doses of oils taken (59 vs 55 mL/d, P = 0.59), or (e) change in seizure frequency (54% vs 102%, P = 0.13). Please note that people with focal unaware seizures were underrepresented in the triheptanoin treatment arm (P = 0.04). The most common adverse events were gastrointestinal disturbances (47% and 62.5% of participants). Five people taking on average 0.73 mL/kg body weight MCTs (0.64 mL/kg median) and one person taking 0.59 mL/kg triheptanoin showed >50% reduction in seizure frequency, specifically focal unaware seizures.SignificanceAdd-on treatment with MCTs or triheptanoin was feasible, safe, and tolerated for 12 weeks in two-thirds of people with treatment-resistant epilepsy. Our results indicate a protective effect of MCTs on focal unaware seizures. This warrants further study.
| S-EPMC6398112 | biostudies-literature
Project description:1. Medium-chain triglyceride (MCT) is often administered to patients with Crohn's disease (CD) or short-bowel syndrome. However, little is known about the effects of medium-chain fatty acids (MCFAs) and MCT on intestinal inflammation. In this study we examined whether caprylic acid, one of the MCFAs, and MCT suppress IL-8 secretion by differentiated Caco-2 cells. 2. We found for the first time that caprylic acid and MCT suppress IL-8 secretion by Caco-2 cells at the transcriptional level when precultured together for 24 h. We also tried to clarify the mechanism of IL-8 gene inhibition by examining the activation of NF-kappaB and other transcription factors by electrophoretic mobility shift assay (EMSA), and found that caprylic acid did not modulate their activation. 3. The result of dual-luciferase assay using Caco-2 cells transfected with IL-8 promoter/luciferase reporter plasmid revealed that caprylic acid inhibited the activation of IL-8 promoter. 4. Similar results were observed when cells were precultured with the well-known potent histone deacetylase inhibitor trichostatin A (TSA). 5. We examined the state of H4 acetylation in IL-8 promoter using the technique known as chromatin immunoprecipitation (Chr-IP). TSA rapidly induced H4 acetylation in IL-8 promoter chromatin, whereas caprylic acid did not. These results suggest that the inhibition of IL-8 gene transcription induced by caprylic acid and TSA does not necessarily require the marked suppression of transcription factors, and the mechanism of inhibition of IL-8 gene transcription may be different between caprylic acid and TSA.
| S-EPMC1573354 | biostudies-other
Project description:ObjectiveMedium chain triglycerides (MCT) have unique metabolic properties which may improve insulin sensitivity (Si) and beta cell function but data in humans are limited. We conducted a 6-week clinical trial of MCT oil supplementation.Methods22 subjects without diabetes (8 males, 14 females, mean ± standard error age 39±2.9 years, baseline BMI 27.0±1.4 kg/m2) were counseled to maintain their body weight and physical activity (PA) during the trial. Dietary intake, PA data, body composition, and resting energy expenditure (REE) were obtained through dietary recall, international PA questionnaire, dual x-ray absorptiometry, and indirect calorimetry, respectively. MCT prescriptions were given based on REE and PA to replace part of dietary fat with 30 grams of MCT per 2000 kcal daily. Insulin-modified frequently sampled intravenous glucose tolerance tests were performed before and after MCT to measure changes in Si, acute insulin response (AIR), disposition index (DI), and glucose effectiveness (Sg).ResultsMCT were well tolerated and weight remained stable (mean change 0.3 kg, p = 0.39). Fasting REE, respiratory quotient, and body composition were stable during the intervention. There were no significant changes in mean fasting glucose, insulin, insulin resistance, fasting total ketones, Si, AIR, DI, Sg, leptin, fructosamine, and proinsulin. The mean change in Si was 0.5 10-4 min-1 per mU/L (95% CI: -1.4, 2.4), corresponding to a 12% increase from baseline, and the range was -4.7 to 12.9 10-4 min-1 per mU/L. Mean total adiponectin decreased significantly from 22925 ng/mL at baseline to 17598 ng/mL at final visit (p = 0.02). The baseline clinical and laboratory parameters were not significantly associated with the change in Si.DiscussionThere were a wide range of changes in the minimal model parameters of glucose and insulin metabolism in subjects following 6 weeks of MCT as an isocaloric substitution for part of usual dietary fat intake. Since this was a single-arm non-randomized study without a control group, it cannot be certain whether these changes were due to MCT so further randomized controlled trials are warranted.
| S-EPMC6927614 | biostudies-literature
Project description:Obesity can be associated with significant metabolic disorders. Our previous study found that medium-chain triglycerides (MCTs) improved lipid metabolism in obese rats. However, scant attention has been given to exploring the impact of MCTs on glucose metabolism in obese rats. This study is designed to examine the effects and mechanisms of three distinct MCTs on glucose metabolism in obese rats. To induce obesity, Sprague-Dawley (SD) rats were fed a high-fat diet, followed by a 12-week treatment with caprylic triglyceride (CYT), capric triglyceride (CT), and lauric triglyceride (LT). The results showed that three types of MCT intervention reduced the levels of lipids (TC, TG, LDL-c, and HDL-c), hyperglycemia, insulin resistance (insulin, OGTT, HOMA-IR, and ISI), and inflammatory markers (IL-4, IL-1β, and TNF-α) in obese rats (p < 0.01), The above parameters have been minimally improved in the high-fat restoring group (HR) group. MCTs can modulate the PI3K/AKT signaling pathways to alleviate insulin resistance and improve glucose metabolism in obese rats. Furthermore, MCTs can activate peroxisome proliferator-activated receptor (PPAR) γ and reduce the phosphorylation of PPARγser237 mediated by CDK5, which can improve insulin sensitivity without lipid deposition in obese rats. Among the MCT group, CT administration performed the best in the above pathways, with the lowest blood glucose level and insulin resistance. These findings contribute to a deeper understanding of the connection between health benefits and the specific type of MCT employed.
| S-EPMC10815142 | biostudies-literature