Effects of a low carbohydrate ketogenic diet on the expression of genes in mouse tissues
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ABSTRACT: Low carbohydrate ketogenic diet (LCKD) has been used for treatment obesity and epilepsy, however, the molecular mechanism of effect of a LCKD (F3666) on tissues has not been fully investigated. In this study, novel molecular targets of LCKD were explored by gene expression profiling in the liver and cerebral cortex of an LCKD-fed mouse model.
Project description:The ketogenic diet has long been used to treat epilepsy, but its mechanism is not yet clearly understood. To explore the potential mechanism, the changes in gene expression induced by the ketogenic diet in the rat kainic acid (KA) epilepsy model were analyzed. Two-condition experiment, Normal diet-fed rat brain vs. Ketogenic diet-fed rat brain. Duplicate per array
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.
Project description:The ketogenic diet has long been used to treat epilepsy, but its mechanism is not yet clearly understood. To explore the potential mechanism, the changes in gene expression induced by the ketogenic diet in the rat kainic acid (KA) epilepsy model were analyzed.
Project description:Metaproteomics is a valuable approach to characterize the biological functions involved in the gut microbiota (GM) response to dietary interventions. Ketogenic diets (KDs) are very effective in controlling seizure severity and frequency in drug-resistant epilepsy (DRE) and in the weight loss management in obese/overweight individuals. This case study provides proof of concept for the suitability of metaproteomics to monitor changes in taxonomic and functional GM features in an individual on a short-term very low-calorie ketogenic diet (VLCKD, 4 weeks), followed by a low-calorie diet (LCD). A marked increase in Akkermansia and Pseudomonadota was observed during VLCKD and reversed after the partial reintroduction of carbohydrates (LCD), in agreement with the results of previous metagenomic studies. In functional terms, the relative increase in Akkermansia was associated with an increased production of proteins involved in response to stress and biosynthesis of gamma-aminobutyric acid. In addition, VLCKD caused a relative increase in enzymes involved in the synthesis of the beta-ketoacid acetoacetate and of the ketogenic amino acid leucine. Our data support the potential of fecal metaproteomics to investigate the GM-dependent effect of KD as a therapeutic option in obese/overweight individuals and DRE patients.
Project description:We demonstrate that the ketogenic diet a low carbohydrate diet can induce fibrosis and NASH regardless of body weight loss compared to high-fat diet (HFD) fed mice. KD-fed mice develop severe hepatic injury, inflammation, and steatosis. In addition, KD increases IL-6-JNK signaling and aggravates diet induced-glucose intolerance and hepatic insulin resistance compared to HFD. Notably, pharmacological inhibition of IL-6 and JNK reverses KD‐induced glucose intolerance and restores insulin sensitivity.
Project description:The Ketogenic Diet (KD) was shown to extend lifespan and preserve memory in aged mice. We carried out RNA-seq on brains of mice aged 13-26 months on standard Carbohydrate-rich control Diet (CD) vs KD, to better understand KD's mechanism for memory preservation.
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.
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.
Project description:Specific pathogen free wild-type C57Bl/6 male mice fed ketogenic diet (Bio-Serv AIN-76-A) for 4 weeks Keywords: RNA Expression Array Hearts from 12 week-old mice that were maintained on a standard polysacchardide-rich chow until the age of 8 weeks, at which time they were switched to a ketogenic diet (ad libitum) and maintained for 4 additional weeks prior to collection of tissues