Gene expression profiling of mouse liver after a ketogenic diet (KD)
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE238099 | GEO | 2023/07/29
REPOSITORIES: GEO
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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:To investigate the impact of ketogenesis, we subjected 3-month-old mice with either a ketogenic diet (KD) or a control diet (Ctrl) group for 9 weeks. Similar to previous studies, KD led to a significantly decreased mice weight (Fig. 1b). Furthermore, adherence to a KD dramatically elevated blood β-OHB <<28877458/28877456>> and decreased blood glucose <33838492> (Fig. 1c, d). To investigate how KD affected mice liver proteomes post-translationally, we probed the liver tissues with various pan-PTM antibodies. KD dramatically increased the global levels of Kbhb, acetylation (Kac), and O-GlcNAcylation, with the level of Kbhb increased most (6 fold relative to control). On the other hand, KD led to the decreased levels of lactylation and succinylation, but did not alter the levels of phosphorylation, ubiquitination and sumoylation.For label-free proteomic and β-hydroxybutyrylomic quantifications, 6 liver samples of Ctrl or KD mice were pooled into two samples, and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). For metabolomic profilling, 6 liver samples from Ctrl or KD mice were also adopted for untargeted metabolomic profiling in Ctrl and KD mice, respectively.
2023-07-24 | PXD044027 | iProX
Project description:Epilepsy affects between 1-2% of people worldwide and is defined symptomatically by the appearance of spontaneous, recurrent seizures. The ketogenic diet (KD) is an anticonvulsant treatment that has been used to manage medically-intractable epilepsies. Both clinical and experimental reports show that the KD can be used to treat a variety of seizure types. During KD treatment, ketone bodies, rather than glucose, become the major energy substrate for the brain; somehow, metabolic conversion confers a potent anticonvulsant effect. The KD requires 10-12 days to become maximally effective, suggesting that changes in gene expression are involved in its anticonvulsant action. Despite its use for over 80 years, the mechanism of the diet remains unknown. It is expected that this work will help elucidate the underlying anticonvulsant action of the KD and contribute to future, rationale-based drug development. We propose to identify sets of genes activated/repressed within hippocampus after treatment with a KD. We hypothesize that gene expression patterns induced by alterations in metabolic pathways are critically involved with the anticonvulsant effects of the KD in mice. Mice (n=44, 129svJ) will be used for these experiments. Animals will be fed either a KD (n=22) or control diet (n=22) for 14 days. After this time, ten animals from each group will be subjected to flurothyl seizure testing to confirm seizure threshold elevation. Of the remaining KD- (n=12) or control-fed (n=12) animals, two left hippocampi will be pooled together such that six arrays from each treatment group can be tested. This is expected to reduce biological variability. Right hippocampi (n=12/group) will be maintained in our lab for corroborative analysis via RT-PCR and immunohistochemistry. All tissue samples will be rapidly dissected, frozen in liquid nitrogen, and stored at -80C until shipping/corroborative testing. Data analysis will be completed with Significance of Array Measurement (SAM) program using ANOVA from protection for multiple comparisons. Please use the Affy chip with known genes in lieu of the chip containing mostly EST's.
2008-06-11 | E-GEOD-1829 | biostudies-arrayexpress
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
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:The circadian clock orchestrates rhythms in physiology and behavior, allowing the organism to adapt to daily environmental changes. Recently, efforts have been made to unravel the connection between the circadian clock and metabolism and to understand how the peripheral clock in different organs coordinates circadian responses to maintain metabolic homeostasis. It is becoming clear that diet can influence diurnal rhythms, however, the molecular mechanisms responsible for alterations in daily oscillations and how tissue-specific clocks interpret a nutritional challenge are not well understood. Here, we reveal tissue-specific circadian plasticity in response to a ketogenic diet (KD) in both the liver and intestine and a remarkable deviation within these two tissues following subsequent carbohydrate supplementation. KD caused a dramatic change in the circadian transcriptome in both liver and intestine in a tissue-specific fashion. In particular, both the amplitude of clock genes as well as specific BMAL1 recruitment was profoundly altered by KD while the intestinal clock was devoid of such plasticity. While PPARG nuclear accumulation was circadian in both tissues, it showed substantial phase specificity as did downstream targets. Finally, the gut and liver clocks had distinct responses to carbohydrate supplementation to KD composition, suggesting a higher plasticity in the ileum whose gene expression was almost restored to control baseline. For the first time our results demonstrate how nutrients modulate clock function in a tissue-specific manner, suggesting that a food stress arouses unique circadian molecular signatures in distinct peripheral tissues.
2017-09-18 | GSE87425 | 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 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: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:The application of ketogenic diet (KD) (high fat/low carbohydrate/adequate protein) as an auxiliary cancer therapy is a field of growing attention. KD provides sufficient energy supply for healthy cells, while possibly impairing energy production in highly glycolytic tumor cells. Moreover, KD regulates insulin and tumor related growth factors (like insulin growth factor-1, IGF-1). In order to provide molecular evidence for the proposed additional inhibition of tumor growth when combining chemotherapy with KD, we applied untargeted quantitative metabolome analysis on a spontaneous breast cancer xenograft mouse model, using MDA-MB-468 cells. Healthy mice and mice bearing breast cancer xenografts and receiving cyclophosphamide chemotherapy were compared after treatment with control diet and KD. Metabolomic profiling was performed on plasma samples, applying high-performance liquid chromatography coupled to tandem mass spectrometry. Statistical analysis revealed metabolic fingerprints comprising numerous significantly regulated features in the group of mice bearing breast cancer. This fingerprint disappeared after treatment with KD, resulting in recovery to the metabolic status observed in healthy mice receiving control diet. Moreover, amino acid metabolism as well as fatty acid transport were found to be affected by both the tumor and the applied KD. Our results provide clear evidence of a significant molecular effect of adjuvant KD in the context of tumor growth inhibition and suggest additional mechanisms of tumor suppression beyond the proposed constrain in energy supply of tumor cells.
2019-10-08 | MTBLS1066 | MetaboLights
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.
2023-01-31 | GSE218025 | GEO