Medium-chain triglycerides improve cognition and systemic metabolism in Alzheimer mice II
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PROVIDER: PRJNA1209942 | ENA |
REPOSITORIES: ENA
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Project description:Medium-chain triglycerides improve cognition and systemic metabolism in Alzheimer mice
| PRJNA1271131 | ENA
Project description:Medium-chain triglycerides improve cognition and systemic metabolism in Alzheimer mice I
| PRJNA1141441 | ENA
Project description:Lifestyle-based interventions, including dietary modifications, can reduce dementia risk. In this regard, dietary supplementation with medium-chain triglycerides (MCT) shows promise against Alzheimer’s disease in humans. This effect is widely presumed to be mediated by hepatic conversion of MCT into circulating ketones. However, the physiological and cellular mechanisms underlying the benefits of MCT remain understudied, particularly in the context of Alzheimer’s disease. Here, we investigated the cellular and molecular changes occurring in the brain and systemically in response to dietary supplementation with MCT versus a classic ketogenic diet (KD). The experimental design consisted of comparing a 70% carbohydrate control diet to either a control diet supplemented with 10% MCT or a carbohydrate-free high fat KD. Diets were tested in two Alzheimer’s disease mouse models, slow-progressing 3xTg-AD mice that model pre-symptomatic/early stages and rapidly-progressing 5xFAD mice that model late stages of the disease. We found that MCT supplementation and KD both improved hippocampal-dependent spatial learning and memory, increased dendritic spine density of hippocampal neurons, and modulated hippocampal expression of genes associated with mitochondrial functions, synaptic structure, and insulin signaling in Alzheimer’s disease mouse models. However, unlike KD,MCT supplementation did not elevate circulating ketones, suggesting different mechanisms. Indeed, while MCT enhanced the peripheral insulin response of Alzheimer’s disease mice, KD conversely unveiled their latent metabolic vulnerability, increasing their hyperglycemia, body weight gain, and adiposity. The systemic metabolic disturbances of Alzheimer’s disease mice correlated with transcriptomic alterations in hepatic lipid metabolism and ketogenesis genes and increased lipid droplet accumulation. These liver metabolic abnormalities were partially reversed by both MCT supplementation and KD, but in distinct ways. Notably, KD selectively triggered hepatic neutral lipid depletion and prominent proinflammatory gene expression while MCT down-regulated expression of cholesterol-related genes. Collectively, these findings reveal that MCT supplementation in the context of Alzheimer’s disease improves cognition and systemic metabolism without elevating circulating ketone levels.
2025-08-11 | GSE286571 | GEO
Project description:Lifestyle-based interventions, including dietary modifications, can reduce dementia risk. In this regard, dietary supplementation with medium-chain triglycerides (MCT) shows promise against Alzheimer’s disease in humans. This effect is widely presumed to be mediated by hepatic conversion of MCT into circulating ketones. However, the physiological and cellular mechanisms underlying the benefits of MCT remain understudied, particularly in the context of Alzheimer’s disease. Here, we investigated the cellular and molecular changes occurring in the brain and systemically in response to dietary supplementation with MCT versus a classic ketogenic diet (KD). The experimental design consisted of comparing a 70% carbohydrate control diet to either a control diet supplemented with 10% MCT or a carbohydrate-free high fat KD. Diets were tested in two Alzheimer’s disease mouse models, slow-progressing 3xTg-AD mice that model pre-symptomatic/early stages and rapidly-progressing 5xFAD mice that model late stages of the disease. We found that MCT supplementation and KD both improved hippocampal-dependent spatial learning and memory, increased dendritic spine density of hippocampal neurons, and modulated hippocampal expression of genes associated with mitochondrial functions, synaptic structure, and insulin signaling in Alzheimer’s disease mouse models. However, unlike KD,MCT supplementation did not elevate circulating ketones, suggesting different mechanisms. Indeed, while MCT enhanced the peripheral insulin response of Alzheimer’s disease mice, KD conversely unveiled their latent metabolic vulnerability, increasing their hyperglycemia, body weight gain, and adiposity. The systemic metabolic disturbances of Alzheimer’s disease mice correlated with transcriptomic alterations in hepatic lipid metabolism and ketogenesis genes and increased lipid droplet accumulation. These liver metabolic abnormalities were partially reversed by both MCT supplementation and KD, but in distinct ways. Notably, KD selectively triggered hepatic neutral lipid depletion and prominent proinflammatory gene expression while MCT down-regulated expression of cholesterol-related genes. Collectively, these findings reveal that MCT supplementation in the context of Alzheimer’s disease improves cognition and systemic metabolism without elevating circulating ketone levels.
2025-08-11 | GSE273337 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2025-08-09 | GSE298797 | GEO
Project description:Restoring hippocampal glucose metabolism rescues cognition across Alzheimer disease pathologies
| PRJNA1030024 | ENA
Project description:Brain glucose hypometabolism is a common feature of Alzheimer's disease (AD). Previous studies have shown that cognition is improved by providing AD patients with an alternate energy source: ketones derived from either ketogenic diet or supplementation with medium chain triglycerides (MCT). Recently, data on the neuroprotective capacity of MCT-derived medium chain fatty acids (MCFA) suggest 8-carbon and 10-carbon MCFA may have cognition-enhancing properties which are not related to ketone production. We investigated the effect of 8 week treatment with MCT8, MCT10 or sunflower oil supplementation (5% by weight of chow diet) in 21 month old Wistar rats. Both MCT diets increased ketones plasma similarly compared to control diet, but MCT diets did not increase ketones in the brain. Treatment with MCT10, but not MCT8, significantly improved novel object recognition memory compared to control diet, while social recognition increased in both MCT groups. MCT8 and MCT10 diets decreased weight compared to control diet, where MCFA plasma levels were higher in MCT10 groups than in MCT8 groups. Both MCT diets increased IRS-1 (612) phosphorylation and decreased S6K phosphorylation (240/244) but only MCT10 increased Akt phosphorylation (473). MCT8 supplementation increased synaptophysin, but not PSD-95, in contrast MCT10 had no effect on either synaptic marker. Expression of Ube3a, which controls synaptic stability, was increased by both MCT diets. Cortex transcription via qPCR showed that immediate early genes related to synaptic plasticity (arc, plk3, junb, egr2, nr4a1) were downregulated by both MCT diets while MCT8 additionally down-regulated fosb and egr1 but upregulated grin1 and gba2. These results demonstrate that treatment of 8- and 10-carbon length MCTs in aged rats have slight differential effects on synaptic stability, protein synthesis and behavior that may be independent of brain ketone levels.
| S-EPMC4982641 | biostudies-literature
Project description:BackgroundKetosis has been exploited for its neuroprotective impact and treatment of neurological conditions via ketone production. Exogenous medium-chain triglyceride (MCT) supplementation may induce nutritional ketosis. The aim of this systematic review is to explore the effects of MCTs on memory function in older adults without cognitive impairment.MethodsA systematic literature search of PubMed, Cochrane Library, Scopus, and Web of Science was employed from inception until April 2022 for randomized controlled trials (RCTs) in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, investigating the impact of MCT oils on components of memory. Risk of bias (RoB2) tool was utilized for quality assessment.ResultsSix trials were included for qualitative synthesis, in which two studies examined the effect of MCTs through a ketogenic meal. MCT supplementation compared to controls was associated with improved indices of memory function in 4 out of 6 studies, particularly working memory. A meta-analysis was not employed due to the low number of studies, therefore, a true effect measure of MCT supplementation was not explored.ConclusionsMCT supplementation may enhance working memory in non-demented older adults. These effects may be more prominent in individuals with lower baseline scores, from short and long-term supplementation. Further studies are warranted to confirm these findings in terms of optimal dose and MCTs composition, which may protect from memory decline during aging.
| S-EPMC9588230 | biostudies-literature
Project description:An early settlement of a complex gut microbiota can protect against gastro-intestinal dysbiosis, but the effects of neonatal microbiota colonization and early life feeding of medium chain triglycerides on the maturation of the porcine gastric mucosa are largely unknown. The transcriptome of the oxyntic mucosa of 24 caesarian-derived pigs previously associated with microbiota of different complexity and fed a diet fortified or not with medium chain fatty acids was studied. Pigs received pasteurized sow colostrum at birth (d0), 2 mL of starter microbiota (10^7 CFU of each Lactob. Amylovorus (LAM), Clostr. glycolicum, and Parabacteroides spp.) on d1-d3 of age and either a placebo inoculant (simple association, SA) or an inoculant consisting of diluted feces of an adult sow (complex association, CA) on d3-d4 of age. Then half of pigs was fed a moist diet (CON) or, for the remaining half, CTRL fortified in medium chain triglycerides with 7% coconut oil ( MCT). Gastric samples were obtained at on euthanised pigs at 3 weeks of age.
2016-09-21 | GSE87125 | GEO
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