Effect of Beta-Hydroxybutyrate on Gene Expression in Immunotherapy and Castration Resistant Prostate Cancer Cells
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE206297 | GEO | 2024/02/13
REPOSITORIES: GEO
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Project description:Anorexia and fasting are host adaptations to acute infection, inducing a metabolic switch towards ketogenesis and the production of ketone bodies, including β-hydroxybutyrate (BHB). However, whether ketogenesis metabolically influences the immune response in pulmonary infections remains unclear. Here we report impaired production of BHB in humans with SARS-CoV-2-induced but not influenza-induced acute respiratory distress syndrome (ARDS). BHB promotes the survival and the production of Interferon-g from CD4+ T cells. Using metabolic tracing analysis, we uncovered that BHB provides an alternative carbon source to fuel oxidative phosphorylation (OXPHOS) and the production of bioenergetic amino acids and glutathione, which is important for maintaining the redox balance. T cells from patients with SARS-CoV-2-induced ARDS were exhausted and skewed towards glycolysis, but can be metabolically reprogrammed by BHB to perform OXPHOS, thereby increasing their functionality. Finally, we find that ketogenic diet (KD) reduced pulmonary fibrosis, a feature particular pronounced in COVID-19 ARDS and delivery of BHB as ketone ester drink reduces the mortality of SARS-CoV-2 infected mice. Altogether, our data suggest that impaired ketogenesis in patients with SARS-CoV-2 infection accounts, at least partially for disease progression and that supplementation ketone ester might represent an easy-to-implement treatment to improve the clinical outcome of COVID-19 patients.
2022-07-01 | GSE207077 | GEO
Project description:Diets characterized by increased blood levels of ketone bodies can protect the brain against a variety of acute and chronic neurological diseases. Moreover, ketone bodies are neuroprotective in many in vitro models of neurological injury. The underlying mechanisms remain unknown however. Recently, we have shown that ketone bodies do not only decrease neuronal injury and death but also protect long-term potentiation in acute hippocampal slices exposed to oxidative stress in the form of exogenous hydrogen peroxide. Elucidating the mechanisms behind the effects of ketone bodies on neuronal survival and function will undoubtedly lead to the development of novel neuroprotective treatments. Our aim is to determine acute changes in gene expression of CA1 pyramidal neurons exposed to various duration of the ketone bodies acetoacetate and beta-hydroxybutyrate. CA1 hippocampal pyramidal neurons exposed to oxidative stress do not display any long-term potention following burst stimulation of Schaffer collaterals. Incubation with the ketone bodies acetoacetate and beta-hydroxybutyrate for at least 20 min prior to hydrogen peroxide application restores long-term potentiation to control levels. We hypothesize that the neuroprotective effects of ketone bodies are mediated by changes in gene expression. Acute hippocampal slices (400 microns in thickness) were obtained from 4 week-old rats and exposed to acetoacetate and beta-hydroxybutyrate (1 mM each) for 1 h and 6 h. A control group was incubated in artificial cerebrospinal fluid only. After treatment, the hippocampal slices were used immediately for RNA isolation. Isolated RNA was sent for analysis. Each sample sent for analysis included tissue from 7 separate animals. Hybridization to an Affymetrix array is being performed 3 times for each experimental condition.
2008-06-15 | E-GEOD-7323 | biostudies-arrayexpress
Project description:Diets characterized by increased blood levels of ketone bodies can protect the brain against a variety of acute and chronic neurological diseases. Moreover, ketone bodies are neuroprotective in many in vitro models of neurological injury. The underlying mechanisms remain unknown however. Recently, we have shown that ketone bodies do not only decrease neuronal injury and death but also protect long-term potentiation in acute hippocampal slices exposed to oxidative stress in the form of exogenous hydrogen peroxide. Elucidating the mechanisms behind the effects of ketone bodies on neuronal survival and function will undoubtedly lead to the development of novel neuroprotective treatments. Our aim is to determine acute changes in gene expression of CA1 pyramidal neurons exposed to various duration of the ketone bodies acetoacetate and beta-hydroxybutyrate. CA1 hippocampal pyramidal neurons exposed to oxidative stress do not display any long-term potention following burst stimulation of Schaffer collaterals. Incubation with the ketone bodies acetoacetate and beta-hydroxybutyrate for at least 20 min prior to hydrogen peroxide application restores long-term potentiation to control levels. We hypothesize that the neuroprotective effects of ketone bodies are mediated by changes in gene expression. Acute hippocampal slices (400 microns in thickness) were obtained from 4 week-old rats and exposed to acetoacetate and beta-hydroxybutyrate (1 mM each) for 1 h and 6 h. A control group was incubated in artificial cerebrospinal fluid only. After treatment, the hippocampal slices were used immediately for RNA isolation. Isolated RNA was sent for analysis. Each sample sent for analysis included tissue from 7 separate animals. Hybridization to an Affymetrix array is being performed 3 times for each experimental condition. Keywords: dose response
2007-03-20 | GSE7323 | GEO
Project description:The experiment was carried out in triplicates in untreated, etomoxir treated and etomoxir plus beta-hydroxybutyrate (3HB) treated conditions. MES83 (Glioma-derived Mesenchymal stem cells) were either untreated or treated with 40uM of etomoxir alone or in combination with 0.5mM of beta-hydroxybutyrate for 48 hrs. The cells were collected and total RNA was extracted and the library was prepared according to the manufacturer protocol.
2020-03-31 | E-MTAB-8017 | biostudies-arrayexpress
Project description:The aim of this study is to assess the feasibility of beta-hydroxybutyrate (BHB) supplementation in individuals who are undergoing a standard-of-care colonoscopy or flexible sigmoidoscopy.
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Project description:There is currently no established treatment for Cockayne syndrome, a disease characterized by progressive early onset neurodegeneration with features of premature aging and death in childhood. Here, we tested if acetyl-CoA precursors, citrate and beta-hydroxybutyrate, could reduce features of Cockayne syndrome. We identified the gene Helicase 89B (Hel89B) as a homologue of CSB in drosophila and found that the ketone beta-hydroxybutyrate rescued features of premature aging in Hel89B deficient flies. In mammals, loss of the citrate carrier Indy exacerbated the phenotype of Csbm/m mice, rescued by a ketogenic diet. The rescue effect appeared to be mediated through ketone stimulated histone acetylation and facilitation of transcriptional resolution of non-B DNA. Notably, this appears to be a common effect of a ketogenic diet.
2024-01-01 | GSE207368 | GEO
Project description:Various forms of fasting, including time-restricted feeding, alternate day fasting, and periodic fasting have shown promise in clinical and pre-clinical studies to normalize body weight, improve metabolic health, and protect against disease. Recent studies suggest that β-hydroxybutyrate (βOHB), a characteristic ketone body of the fasted metabolic state, acts as a potential signaling molecule mediating the beneficial effects of the various forms of fasting, potentially by acting as a histone deacetylase inhibitor. In the first part we investigated whether βOHB, in comparison to the well-established histone deacetylase inhibitor butyrate, influences cellular differentiation in vitro. In C2C12 myotubes, 3T3-L1 adipocytes, and THP-1 monocytes, millimolar concentrations of βOHB did not alter differentiation, as determined by gene expression and histological assessment, whereas equimolar concentrations of butyrate potently impaired differentiation in all cell types. RNA-sequencing revealed that unlike butyrate, βOHB minimally impacted gene expression in adipocytes, macrophages, and hepatocytes. However, in myocytes, βOHB upregulated genes involved in the TCA cycle and oxidative phosphorylation, while downregulating genes belonging to cytokine and chemokine signal transduction. Overall, our data do not support the notion that βOHB serves as a powerful signaling molecule regulating gene expression in adipocytes, macrophages and hepatocytes, but suggest that βOHB may act as a niche signaling molecule in muscle.
2021-08-10 | GSE179023 | GEO
Project description:Family with sequence similarity 172 member A (FAM172A) protein acts as a key physiological repressor of brown adipose tissue (BAT) activity that plays a key role in energy metabolism. Its expression in BAT is suppressed by cold and other adrenergic stimulators. Mechanistically, FAM172A inhibits BAT activity and thermogenesis, in part, by binding to 3-hydroxybutyrate dehydrogenase 1 (BDH1), which subsequently affects the levels of beta-hydroxybutyrate (BHB), a ketone body metabolite closely involved in adipose mitochondrial biogenesis.
2023-08-29 | GSE241732 | GEO
Project description:Investigating the gene expression profile changes upon β-hydroxybutyrate treatment in MDA-MB-231 breast cancer cells w/ or w/o MCT2 expression
2017-06-13 | GSE84053 | GEO
Project description:Lysine -hydroxybutyrylation (Kbhb) is a newly identified protein post-translational modification that derived from the ketone body β-hydroxybutyrate (BHB). BHB is synthesized in the liver from fatty acids and could be delivered to peripheral tissues when the supply of glucose is too low for the body’s energetic needs. The plasma concentration of BHB can increase up to 20 mM during starvation and in pathological conditions. Despite the progresses, how the cells that do not produce BHB respond to elevated environmental BHB remains largely unknown. Given that BHB significantly drives Kbhb, here we performed a quantitative proteomics study to characterize the BHB-induced lysine -hydroxybutyrylome and acetylome. A total of 840 unique Kbhb sites across 429 proteins were identified, with 42 sites from 39 proteins being increased by more than 50% in response to BHB. The upregulated β-hydroxybutyrylome induced by BHB are involved in aminoacyl-tRNA biosynthesis, 2-oxocarboxylic acid metabolism, citrate cycle (TCA cycle), glycolysis/gluconeogenesis, and pyruvate metabolism pathways. Moreover, some BHB-targeted Kbhb substrates are potentially linked to diseases such as cancer. Taken together, this study revealed the dynamics of lysine -hydroxybutyrylome and acetylome in response to environmental BHB, which sheds light on the roles for Khib in regulation of diverse cellular processes and provides new insights into the biological functions of BHB.
2022-04-04 | PXD029481 | Pride