Ketogenic Diet Decreases Alcohol Intake in Adult Male Mice

The classic ketogenic diet is a diet high in fat, low in carbohydrates, and well-adjusted proteins. The reduction in glucose levels induces changes in the body’s metabolism, since the main energy source happens to be ketone bodies. Recent studies have suggested that nutritional interventions may modulate drug addiction. The present work aimed to study the potential effects of a classic ketogenic diet in modulating alcohol consumption and its rewarding effects. Two groups of adult male mice were employed in this study, one exposed to a standard diet (SD, n = 15) and the other to a ketogenic diet (KD, n = 16). When a ketotic state was stable for 7 days, animals were exposed to the oral self-administration paradigm to evaluate the reinforcing and motivating effects of ethanol. Rt-PCR analyses were performed evaluating dopamine, adenosine, CB1, and Oprm gene expression. Our results showed that animals in a ketotic state displayed an overall decrease in ethanol consumption without changes in their motivation to drink. Gene expression analyses point to several alterations in the dopamine, adenosine, and cannabinoid systems. Our results suggest that nutritional interventions may be a useful complementary tool in treating alcohol-use disorders.

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Exposure to Bisphenol-A during Pregnancy Partially Mimics the Effects of a High-Fat Diet Altering Glucose Homeostasis and Gene Expression in Adult Male Mice

PLoS ONE ◽

10.1371/journal.pone.0100214 ◽

2014 ◽

Vol 9 (6) ◽

pp. e100214 ◽

Cited By ~ 98

Author(s):

Marta García-Arevalo ◽

Paloma Alonso-Magdalena ◽

Junia Rebelo Dos Santos ◽

Ivan Quesada ◽

Everardo M. Carneiro ◽

...

Keyword(s):

Gene Expression ◽

Bisphenol A ◽

Glucose Homeostasis ◽

Adult Male ◽

High Fat Diet ◽

Male Mice ◽

High Fat

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Maintenance of Energy Homeostasis during Calorically Restricted Ketogenic Diet and Fasting-MR-Spectroscopic Insights from the ERGO2 Trial

Cancers ◽

10.3390/cancers12123549 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3549

Author(s):

Katharina J. Wenger ◽

Marlies Wagner ◽

Patrick N. Harter ◽

Kea Franz ◽

Jörg Bojunga ◽

...

Keyword(s):

Ketogenic Diet ◽

Energy Homeostasis ◽

Tumor Tissue ◽

Ketone Bodies ◽

Basis Set ◽

Intermittent Fasting ◽

Standard Diet ◽

Significant Difference ◽

Group A ◽

Group B

Background: The ERGO2 (Ernaehrungsumstellung bei Patienten mit Rezidiv eines Glioblastoms) MR-spectroscopic imaging (MRSI) subtrial investigated metabolism in patients randomized to calorically restricted ketogenic diet/intermittent fasting (crKD-IF) versus standard diet (SD) in addition to re-irradiation (RT) for recurrent malignant glioma. Intracerebral concentrations of ketone bodies (KB), intracellular pH (pHi), and adenosine triphosphate (ATP) were non-invasively determined. Methods: 50 patients were randomized (1:1): Group A keeping a crKD-IF for nine days, and Group B a SD. RT was performed on day 4–8. Twenty-three patients received an extended MRSI-protocol (1H decoupled 31P MRSI with 3D chemical shift imaging (CSI) and 2D 1H point-resolved spectroscopy (PRESS)) at a 3T scanner at baseline and on day 6. Voxels were selected from the area of recurrent tumor and contralateral hemisphere. Spectra were analyzed with LCModel, adding simulated signals of 3-hydroxybutyrate (βOHB), acetone (Acn) and acetoacetate (AcAc) to the standard basis set. Results: Acn was the only reliably MRSI-detectable KB within tumor tissue and/or normal appearing white matter (NAWM). It was detected in 4/11 patients in Group A and in 0/8 patients in Group B. MRSI results showed no significant depletion of ATP in tumor tissue of patients at day 6 during crKD-IF, even though there were a significant difference in ketone serum levels between Group A and B at day 6 and a decline in fasting glucose in Group A from baseline to day 6. The tumor specific alkaline pHi was maintained. Conclusions: Our metabolic findings suggest that tumor cells maintain energy homeostasis even with reduced serum glucose levels and may generate additional ATP through other sources.

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Ketogenic Diet as a potential treatment for traumatic brain injury in mice

Scientific Reports ◽

10.1038/s41598-021-02849-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Meirav Har-Even ◽

Vardit Rubovitch ◽

Whitney A. Ratliff ◽

Bar Richmond-Hacham ◽

Bruce A. Citron ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Dentate Gyrus ◽

Ketogenic Diet ◽

Cognitive Abilities ◽

Ketone Bodies ◽

Temporal Cortex ◽

Closed Head Injury ◽

Standard Diet ◽

Post Injury

AbstractTraumatic brain injury (TBI) is a brain dysfunction without present treatment. Previous studies have shown that animals fed ketogenic diet (KD) perform better in learning tasks than those fed standard diet (SD) following brain injury. The goal of this study was to examine whether KD is a neuroprotective in TBI mouse model. We utilized a closed head injury model to induce TBI in mice, followed by up to 30 days of KD/SD. Elevated levels of ketone bodies were confirmed in the blood following KD. Cognitive and behavioral performance was assessed post injury and molecular and cellular changes were assessed within the temporal cortex and hippocampus. Y-maze and Novel Object Recognition tasks indicated that mTBI mice maintained on KD displayed better cognitive abilities than mTBI mice maintained on SD. Mice maintained on SD post-injury demonstrated SIRT1 reduction when compared with uninjured and KD groups. In addition, KD management attenuated mTBI-induced astrocyte reactivity in the dentate gyrus and decreased degeneration of neurons in the dentate gyrus and in the cortex. These results support accumulating evidence that KD may be an effective approach to increase the brain’s resistance to damage and suggest a potential new therapeutic strategy for treating TBI.

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Altered Gene Expression and Spine Density in Nucleus Accumbens of Adolescent and Adult Male Mice Exposed to Emotional and Physical Stress

Developmental Neuroscience ◽

10.1159/000362875 ◽

2014 ◽

Vol 36 (3-4) ◽

pp. 250-260 ◽

Cited By ~ 27

Author(s):

Brandon L. Warren ◽

Omar K. Sial ◽

Lyonna F. Alcantara ◽

Maria A. Greenwood ◽

Jacob S. Brewer ◽

...

Keyword(s):

Gene Expression ◽

Nucleus Accumbens ◽

Adult Male ◽

Physical Stress ◽

Spine Density ◽

Male Mice ◽

Altered Gene Expression ◽

Altered Gene

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Ketogenic diet and metabolic regulation of brain microglia

Neuro-Oncology ◽

10.1093/neuonc/noz167.035 ◽

2019 ◽

Vol 21 (Supplement_4) ◽

pp. iv8-iv9

Author(s):

Adrian Benito ◽

Nabil Hajji ◽

Kevin O’Neill ◽

Hector C Keun ◽

Nelofer Syed

Keyword(s):

Immune System ◽

Ketogenic Diet ◽

Brain Tumours ◽

Metabolic Regulation ◽

Ketone Bodies ◽

Tumour Progression ◽

Tumour Mass ◽

Nutritional Interventions ◽

New Knowledge ◽

The Brain

Abstract Ketogenic diet (KD) has been proposed as a coadjuvant therapy in the treatment of brain tumours. Reduction of blood glucose and increase in ketone bodies concentration are amongst the most important changes induced by KD in patients. Preliminary data collected in our lab indicates that KD induces substantial changes in the immune system in mice bearing brain tumours. Microglia are brain-resident immune cells that account for around 30% of the tumour mass and play a major role in controlling tumour progression by adopting a protumour (M2 polarisation) or antitumour (M1 polarisation) phenotype. We are interested in understating the molecular and metabolic determinants of microglia polarisation and how these can be modulated by the metabolic microenvironment and KD. We report some initial findings that indicate microglia adapt to changes in the metabolic microenvironment and that nutrient availability can modulate microglia activation and polarisation. We believe that the study of microglia metabolism and nutritional interventions like KD can provide new knowledge about the regulation of the brain immune system and unveil novel routes for brain cancer treatment.

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Effects of Developmental Arsenic Exposure on the Social Behavior and Related Gene Expression in C3H Adult Male Mice

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph16020174 ◽

2019 ◽

Vol 16 (2) ◽

pp. 174 ◽

Cited By ~ 7

Author(s):

Soe-Minn Htway ◽

Mya-Thanda Sein ◽

Keiko Nohara ◽

Tin-Tin Win-Shwe

Keyword(s):

Gene Expression ◽

Social Behavior ◽

Adult Male ◽

Arsenic Exposure ◽

Receptor Expression ◽

Heme Oxygenase 1 ◽

Male Mice ◽

Related Gene ◽

Gene Expressions ◽

Significant Difference

Arsenic is carcinogenic and teratogenic. In addition, it is also a developmental neurotoxicant. Little is known however about the effect of arsenic exposure during brain development on social behavior. This study aimed to detect the effect of developmental arsenic exposure on social behavior and related gene expression in C3H adult male mice. Pregnant C3H mice were exposed to sodium arsenite (NaAsO2, 85 ppm in the drinking water) from gestational day (GD) 8 to 18. The F1 generation male pups from different mothers were taken and social behavior tasks were examined. Social behavioral-related gene expression in the prefrontal cortex was determined by the real-time RT-PCR method. The mice with developmental arsenic exposure showed poor sociability and poor social novelty preference. Glutamate receptor expression (NMDA and AMPA receptor subunits) showed no significant difference, but gene expressions of serotonin receptor 5B (5-HT 5B) and brain-derived neurotrophic factor (BDNF) were significantly decreased (p < 0.05) in the arsenic-exposed group compared to control group. The heme oxygenase-1 (HO-1) and cyclooxygenase-2 (COX-2) gene expressions were not significantly different. Our findings indicate that developmental arsenic exposure might affect social behavior by modulating serotonin receptors and reducing BDNF. Some oxidative stress markers and inflammatory markers were not affected.

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Investigation of the effect of diazinon on CatSper 1 gene expression, sperm motility and germinal epithelium thickness in adult male mice

Scientific Journal of Kurdistan University of Medical Sciences ◽

10.29252/sjku.24.6.68 ◽

2020 ◽

Vol 24 (6) ◽

pp. 68-78

Author(s):

hamid reza faragnezhad ◽

shabnam mohammadi ◽

seyed morteza Seifati ◽

atena mansouri ◽

reyhaneh mahmoodian ◽

...

Keyword(s):

Gene Expression ◽

Sperm Motility ◽

Adult Male ◽

Germinal Epithelium ◽

Male Mice ◽

Epithelium Thickness

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Rescue of 2-Deoxyglucose Side Effects by Ketogenic Diet

International Journal of Molecular Sciences ◽

10.3390/ijms19082462 ◽

2018 ◽

Vol 19 (8) ◽

pp. 2462 ◽

Cited By ~ 8

Author(s):

Martin Voss ◽

Nadja Lorenz ◽

Anna-Luisa Luger ◽

Joachim Steinbach ◽

Johannes Rieger ◽

...

Keyword(s):

Side Effects ◽

Ketogenic Diet ◽

Cancer Metabolism ◽

Ketone Bodies ◽

Aerobic Glycolysis ◽

Glucose Consumption ◽

Maximum Tolerated Dose ◽

Standard Diet ◽

Sedative Effects

Cancer metabolism is characterized by extensive glucose consumption through aerobic glycolysis. No effective therapy exploiting this cancer trait has emerged so far, in part, due to the substantial side effects of the investigated drugs. In this study, we examined the side effects of a combination of isocaloric ketogenic diet (KD) with the glycolysis inhibitor 2-deoxyglucose (2-DG). Two groups of eight athymic nude mice were either fed a standard diet (SD) or a caloric unrestricted KD with a ratio of 4 g fat to 1 g protein/carbohydrate. 2-DG was investigated in commonly employed doses of 0.5 to 4 g/kg and up to 8 g/kg. Ketosis was achieved under KD (ketone bodies: SD 0.5 ± 0.14 mmol/L, KD 1.38 ± 0.28 mmol/L, p < 0.01). The intraperitoneal application of 4 g/kg of 2-DG caused a significant increase in blood glucose, which was not prevented by KD. Sedation after the 2-DG treatment was observed and a behavioral test of spontaneous motion showed that KD reduced the sedation by 2-DG (p < 0.001). A 2-DG dose escalation to 8 g/kg was lethal for 50% of the mice in the SD and for 0% of the mice in the KD group (p < 0.01). A long-term combination of KD and an oral 1 or 2 g 2-DG/kg was well-tolerated. In conclusion, KD reduces the sedative effects of 2-DG and dramatically increases the maximum tolerated dose of 2-DG. A continued combination of KD and anti-glycolytic therapy is feasible. This is, to our knowledge, the first demonstration of increased tolerance to glycolysis inhibition by KD.

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Ketogenic Diet as a Potential Treatment for Traumatic Brain Injury in Mice

10.21203/rs.3.rs-642407/v1 ◽

2021 ◽

Author(s):

Meirav Har-Even ◽

Vardit Rubovitch ◽

Whitney A. Ratliff ◽

Bruce A. Citron ◽

Chaim G. Pick

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Dentate Gyrus ◽

Ketogenic Diet ◽

Ketone Bodies ◽

Standard Diet ◽

Post Injury ◽

Maze Test ◽

Y Maze ◽

Primary Mouse

Abstract Background: Traumatic brain injury (TBI) is a brain dysfunction without present treatment. Previous studies have shown that animals fed a ketogenic diet (KD) perform better in learning tasks than those fed a standard diet (SD) following brain injury. The goal of this study was to examine whether KD is neuroprotective in a TBI mouse model. Methods: We utilized a closed head injury model to induce mild TBI (mTBI) in mice. Mice were fed KD or SD starting immediately following the trauma and throughout the following 30 days. Tail blood ketone bodies levels were checked at 0, 3, 7 and 30 days post injury. Behavioral tests took place at 7 and 30days post injury, visual and spatial memory impairments were assessed using the Novel object recognition (NOR) paradigm and the Y-maze test, respectively, and anxiety-like behavior was assessed using the elevated plus maze test. Primary mouse SIRT1 levels antibodies were used to detect changes in protein levels following TBI induction and treatments 7 and 30 days post injury and Immunohistochemical sections were stained with, NeuN (for mature neurons), Iba-1 (for microglia) and GFAP (for astrocyte). Results: Elevated levels of ketone bodies were confirmed in the blood following KD. Cognitive and behavioral performance was assessed post injury and molecular and cellular changes were assessed within the temporal cortex and hippocampus. Y‑maze and NOR tasks indicated that mTBI mice maintained on KD displayed better cognitive abilities than mTBI mice maintained on SD. Mice maintained on SD post-injury demonstrated SIRT1 reduction when compared with uninjured and KD groups. In addition, KD management attenuated mTBI-induced microglia activation and astrocyte reactivity in the dentate gyrus and decreased degeneration of neurons in the dentate gyrus and in the cortex. Conclusion: These results support accumulating evidence that KD may be an effective approach to increase the brain’s resistance to damage and suggest a potential new therapeutic strategy for treating mTBI.

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EXTH-01. A SYNGENIC MOUSE MODEL TO STUDY THE EFFICACY OF KETOGENIC DIET IN HIGH GRADE GLIOMAS

Neuro-Oncology ◽

10.1093/neuonc/noz175.335 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi82-vi82

Author(s):

Andrea Salmaggi ◽

Chiara Vasco ◽

Ambra Rizzo ◽

Francesco Padelli ◽

Ileana Zucca ◽

...

Keyword(s):

Tumor Cells ◽

Ketogenic Diet ◽

Tumor Tissue ◽

Metabolic Response ◽

Ketone Bodies ◽

Standard Diet ◽

Normal Brain ◽

Gamma Aminobutyric Acid ◽

In Vitro Proliferation

Abstract Glioblastoma multiforme is the most malignant subtype of brain tumor. Despite multimodal treatment (surgical resection and chemo/radiotherapy) the prognosis remains unsatisfactory. Based on the Warburg hypothesis, ketogenic diet (KD) has been suggested in the treatment of GBM. The syngenic, orthotopic GL261 mouse glioma model was used to evaluate the effects of KD on 7T magnetic resonance imaging/spectroscopy and metabolic response of the tumor to diet. Mice were injected with 10^5 GL261 cells into the caudate nucleus. Following implantation, animals were fed standard chow for five days then were randomly assigned to standard diet or ketogenic diet. 18 days after diet start, mice fed at KD displayed significantly higher plasmatic levels of ketone bodies. Mice fed with KD survived longer than those fed with standard diet (p< 0.05). Decreased concentrations of gamma-aminobutyric acid, N Acetyl Aspartate and N-acetylaspartylglutamate were found in tumor tissue after 9 days from the beginning of the KD diet while a huge increase in beta-hydroxybutyrate (bHB) was detected in tumor tissue as compared to normal brain. The addition of bHB at various concentrations to low-glucose culture medium did not significantly improve GL261 in vitro growth suggesting that this cell line has a limited ability to use bHB as a carbon source. The accumulation of bHB in the tumor tissue in KD fed mice, may suggest either elevated uptake of/release of bHB by tumor cells or inability of tumor cells in this context to use it in mitochondrial metabolism; the latter hypothesis is supported by the observation that GL261 cells did not display an increase in in vitro proliferation when exposed to bHB. The far less evident peak of bHB at MRI spectroscopy in the healthy brain tissue of KD fed mice, on the other hand suggests that normal brain is able to use bHB as energy source.

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