Impact of Ketogenic diet on aging associated gene expression in the brain.
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE230324 | GEO | 2024/10/21
REPOSITORIES: GEO
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Project description:The ketone body β-hydroxybutyrate (BHB) is produced during dietary restriction, fasting, and exercise. A ketogenic diet (KD) results in long-term production of BHB outside of these contexts. We sought to determine a protein-matched, non-obese ketogenic diet (KD) would affect the longevity and healthspan of C57BL/6 male mice. We find that feeding KD every-other-week to prevent obesity (cyclic KD) reduces mid-life mortality but does not affect maximum lifespan. Similar feeding of a non-ketogenic high-fat/low-carbohydrate (HF) diet may have an intermediate effect on mortality. Cyclic KD improves memory performance in old age, while modestly improving composite measures of healthspan. RNAseq gene expression analysis identifies down-regulation of insulin, TOR, and fatty acid synthesis pathways as possible longevity mechanisms common to KD and HF. However, up-regulation of fasting-related PPARα target genes is unique to KD, consistent across tissues, and preserved in old age, suggesting a mechanism for an incremental benefit from KD. In all, we show that a non-obese ketogenic diet improves survival, memory, and healthspan into old age. These gene expression studies were carried out on 12 month-old male C56BL/6 mice from the NIA Aged Rodent Colony, habituated to AIN-93M control diet and then either maintained on this diet or switched for one week to a 75% kcal fat non-ketogenic high-fat diet or a 90% kcal fat ketogenic diet (all diets with 10% kcal from carbohydrates). Tissues were harvested in the middle of the nighttime feeding period (MN-3am).
2017-09-05 | GSE101657 | GEO
Project description:The Ketogenic Diet (KD) improves memory and longevity in aged C57BL/6 mice. We tested 7 months KD vs. control diet (CD) in the mouse Alzheimer's Disease (AD) model APP/PS1. KD significantly rescued Long-Term-Potentiation (LTP) to wild-type levels, not by changing Amyloid-β (Aβ) levels. KD's 'main actor' is thought to be Beta-Hydroxy-butyrate (BHB) whose levels rose significantly in KD vs. CD mice, and BHB itself significantly rescued LTP in APP/PS1 hippocampi. KD's 6 most significant pathways induced in brains by RNAseq all related to Synaptic Plasticity. KD induced significant increases in synaptic plasticity enzymes p-ERK and p-CREB in both sexes, and of brain-derived neurotrophic factor (BDNF) in APP/PS1 females. We suggest KD rescues LTP through BHB's enhancement of synaptic plasticity. LTP falls in Mild-Cognitive Impairment (MCI) of human AD. KD and BHB, because they are an approved diet and supplement respectively, may be most therapeutically and translationally relevant to the MCI phase of Alzheimer's Disease.
2023-12-31 | GSE230469 | GEO
Project description:Influenza A virus (IAV) infection-associated morbidity and mortality are a key global healthcare concern, necessitating the identification of novel therapies capable of reducing the severity of IAV infections. In this study, we show that the consumption of a low-carbohydrate, high-fat ketogenic diet (KD) protects mice from lethal IAV infection and disease. KD feeding resulted in an expansion of γδ T cells in the lung that improved barrier functions, thereby enhancing anti-viral resistance. Expansion of these protective γδ T cells required metabolic adaptation to a ketogenic diet, as neither feeding mice a high-fat high-carbohydrate diet nor providing chemical ketone body substrate that bypasses hepatic ketogenesis protected against infection. Therefore, KD mediated immune-metabolic integration represents a viable avenue towards preventing or alleviating influenza disease.
2019-08-29 | GSE136536 | GEO
Project description:Pancreatic ductal adenocarcinoma (PDAC) continues to be a major health problem. A ketogenic diet (KD), characterized by a very low carbohydrate and high fat composition, has gained attention for its anti-tumor potential. We evaluated the effect and mechanisms of feeding a strict KD alone or in combination with gemcitabine in the autochthonous LSL-KrasG12D/+; LSL- Trp53 R172H/+; Pdx1-Cre (KPC) mouse model. For this purpose, both male and female pancreatic tumor-bearing KPC mice were allocated to a control diet (CD; %kcal: 70% carb, 14% protein, 16% fat), a KD (%kcal: 14% protein, 1% carb, 85% fat), a CD + gemcitabine (CG), or a KD + gemcitabine (KG) group. Mice fed a KD alone or in combination with gemcitabine showed significantly increased blood β-hydroxybutyrate levels compared to mice fed a CD or CG. KPC mice fed a KG had a significant increase in overall median survival compared to KPC mice fed a CD (increased overall median survival by 42%). Interestingly, when the data was disaggregated by sex, the effect of a KG was significant in female KPC mice (60% increase in median overall survival), but not in male KPC mice (28% increase in median overall survival). Mechanistically, the enhanced survival response to a KD combined with gemcitabine was multifactorial, including inhibition of ERK and AKT pathways, regulation of fatty acid metabolism and the modulation of the gut microbiota. In summary, a KD in combination with gemcitabine appears beneficial as a treatment strategy in PDAC in KPC mice, deserving further clinical evaluation.
2022-07-21 | GSE208398 | GEO
Project description:Aging is a complex biological process that compromises brain function and neuronal network activity, leading to cognitive decline and synaptic dysregulation. In recent years, a cyclic Ketogenic Diet (KD) has emerged as a potential treatment to ameliorate cognitive decline by improving memory in aged mice after long-term administration. However, whether short-term cyclic KD administration later in life preserves memory has not been addressed in detail. Accordingly, here we investigated how a short-term cyclic KD starting at 20-23 months-old regulates brain function of aged mice. Behavioral testing and long-term potentiation (LTP) recordings revealed that a cyclic KD improves working memory and hippocampal LTP in 24-27 months-old mice after 16 weeks of treatment. Moreover, the diet also promotes higher dendritic arborization complexity and dendritic spine density in the prefrontal cortex. Furthermore, to elucidate the molecular mechanisms underlying the memory improvements elicited by a cyclic KD, cortical synaptosomes of aged mice fed with this diet for 1 year were analyzed by mass spectrometry. Bioinformatics analysis revealed that long-term cyclic KD administration predominantly modulates the presynaptic compartment by inducing changes in the cAMP/PKA signaling pathway, the synaptic vesicle cycle and the actin/microtubule cytoskeleton. To test these findings in vivo, synaptic proteins from cortices of 24-27 month-old mice fed with control or cyclic KD for 16 weeks were analyzed by western blot. Interestingly, increased Brain Derived Neurotrophic Factor abundance, MAP2 phosphorylation and PKA activity were observed. Overall, we show that a cyclic KD regulates brain function and memory even when it is administered at late mid-life and significantly triggers several molecular features of long-term administration, including the PKA signaling pathway and cytoskeleton dynamics, thus promoting synaptic plasticity at advanced age.
2023-08-08 | MSV000092626 | MassIVE
Project description:To investigate the effects of transplanted pre-ketogenic diet (pre-KD) and post-ketogenic diet (post-KD) human fecal microbiota on recipient germ-free swiss webster brain gene expression profiles
2023-12-01 | GSE225682 | GEO
Project description:Analysis of liver gene transcription during feeding of a ketogenic diet. Ketogenic diets may alter physiologic and metabolic profiles in a direction that favors weight loss. C57BL/6J mice were maintained for six weeks on either chow or ketogenic diet. Mice eating KD had lower weights, 90% reduction in insulin levels and increased energy expenditure compared to animals fed chow. Despite consumption of a very high fat diet serum lipids remained normal. Here we show that consumption of KD shifted liver metabolism to drastically increased fatty acid oxidation. Concurrently, expression of genes involved in fatty acid synthesis were markedly suppressed. Reference: A high fat, ketogenic diet induces a unique metabolic state in mice. Kennedy AR, Pissios P, Out H, Xue B, Asakura K, Furukawa N, Marino FE, Liu FF, Kahn BB, Liberman TA, Maratos-Flier E. in press, 2007, Am J Physiol Metab 292. Experiment Overall Design: Eight week old C57BL/6 mice were fed either chow (Labdiet 5008, Pharmserv) or KD (F3666, Bio-Serv) for six weeks. Livers were harvested in the morning in ad lib fed animals. Total RNA from 2-3 animals in each group was used for Affymetrix analysis.
2007-12-13 | E-GEOD-7699 | biostudies-arrayexpress
Project description:Analysis of liver gene transcription during feeding of a ketogenic diet. Ketogenic diets may alter physiologic and metabolic profiles in a direction that favors weight loss. C57BL/6J mice were maintained for six weeks on either chow or ketogenic diet. Mice eating KD had lower weights, 90% reduction in insulin levels and increased energy expenditure compared to animals fed chow. Despite consumpiton of a very high fat diet serum lipids remained normal. Here we show that consumption of KD shifted liver metabolism to drastically increased fatty acid oxidation. Concurrently, expression of genes involved in fatty acid synthesis were markedly suppressed. Keywords: Hepatic profile
2007-05-04 | GSE7699 | GEO
Project description:Rationale: Sepsis patients suffer from severe metabolic and immunologic dysfunction that may be amplified by standard carbohydrate-based nutritional regimes. We therefore hypothesize that a ketogenic diet improves sepsis treatment. Objectives: We investigated the safety and feasibility of a ketogenic diet in sepsis patients. Methods: We conducted a monocentric open-labeled randomized controlled trial (DRKS00017710) enrolling adult sepsis patients randomly assigned to either ketogenic or standard high-carbohydrate diet for 14 days with follow-up until day 30. The primary outcome measure was β-hydroxybutyrate serum concentration on day 14. Secondary outcomes included safety, clinical and immunological changes. Measurements and Main Results: 40 critically ill septic patients were assigned to the study groups. Increase in β-hydroxybutyrate concentrations from baseline to day 14 was markedly greater under ketogenic diet (1.2 ±0.9) compared to controls (-0.3 ±0.4); estimated mean difference 1.4 (95%-CI 1.0-1.8; p<0.0001). During ketogenic diet, no patient required insulin treatment beyond day 4, whereas 35% to 60% of control patients did (p=0.0095). Metabolic side effects were not observed under ketogenic diet. Ventilation-free (IRR 1.7; 95%-CI: 1.5 to 2.1; p<0.0001), vasopressor-free (IRR 1.7; 95%-CI: 1.5 to 2.0; p<0.0001), dialysis-free (IRR 1.5; 95%-CI: 1.3 to 1.8; p<0.0001), and ICU-free days (IRR 1.7; 95%-CI: 1.4 to 2.1; p<0.0001) significantly increased in patients under ketogenic diet. There was no difference in 30-day mortality. Analyses indicated favorable changes towards immune homeostasis. Conclusions: Ketogenic diet is a feasible and safe nutritional regimen in septic patients promoting recovery from sepsis-related organ dysfunction and could become a new tool in modern treatment concepts.
2024-06-13 | PXD046061 | Pride
Project description:The ketogenic diet (KD) is an anticonvulsant treatment that has been used to manage medically-intractable epilepsies. The KD requires 10-12 days to become maximally effective, suggesting that changes in gene expression are involved in its anticonvulsant action. Using the Affymetrix rat arrays (RAE230A), 6 control samples and 5 KD samples were run.
2007-10-27 | E-GEOD-1155 | biostudies-arrayexpress