scholarly journals Modulation of Cellular Biochemistry, Epigenetics and Metabolomics by Ketone Bodies. Implications of the Ketogenic Diet in the Physiology of the Organism and Pathological States

Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 788 ◽  
Author(s):  
Arkadiusz Dąbek ◽  
Martyna Wojtala ◽  
Luciano Pirola ◽  
Aneta Balcerczyk
Keyword(s):  
Ketogenic Diet ◽  
Alternative Energy ◽  
Cardiovascular Health ◽  
Inflammatory Responses ◽  
Ketone Bodies ◽  
Molecular Signaling ◽  
Post Translational Modifications ◽  
Medical Benefits ◽  
Neuronal Disease ◽  
Cellular Biochemistry

Ketone bodies (KBs), comprising β-hydroxybutyrate, acetoacetate and acetone, are a set of fuel molecules serving as an alternative energy source to glucose. KBs are mainly produced by the liver from fatty acids during periods of fasting, and prolonged or intense physical activity. In diabetes, mainly type-1, ketoacidosis is the pathological response to glucose malabsorption. Endogenous production of ketone bodies is promoted by consumption of a ketogenic diet (KD), a diet virtually devoid of carbohydrates. Despite its recently widespread use, the systemic impact of KD is only partially understood, and ranges from physiologically beneficial outcomes in particular circumstances to potentially harmful effects. Here, we firstly review ketone body metabolism and molecular signaling, to then link the understanding of ketone bodies’ biochemistry to controversies regarding their putative or proven medical benefits. We overview the physiological consequences of ketone bodies’ consumption, focusing on (i) KB-induced histone post-translational modifications, particularly β-hydroxybutyrylation and acetylation, which appears to be the core epigenetic mechanisms of activity of β-hydroxybutyrate to modulate inflammation; (ii) inflammatory responses to a KD; (iii) proven benefits of the KD in the context of neuronal disease and cancer; and (iv) consequences of the KD’s application on cardiovascular health and on physical performance.

scholarly journals The Whitening Effect and Histological Safety of Nonthermal Atmospheric Plasma Inducing Tooth Bleaching

2021 ◽  
Vol 18 (9) ◽  
pp. 4714
Author(s):  
Seoul-Hee Nam ◽  
Byul Bo Ra Choi ◽  
Gyoo-Cheon Kim
Keyword(s):  
Alternative Energy ◽  
Soft Tissues ◽  
Inflammatory Responses ◽  
Color Change ◽  
Atmospheric Pressure Plasma ◽  
Atmospheric Plasma ◽  
Tooth Bleaching ◽  
Histological Evaluation ◽  
Light Sources ◽  
Tooth Color

Various light sources have been applied to enhance the bleaching effect. This study was to identify the histological evaluation in oral soft tissues, as well as tooth color change after tooth bleaching by nonthermal atmospheric pressure plasma (NAPP). Nine New Zealand adult female rabbits were randomly divided into three groups (n = 3): group 1 received no treatment; group 2 was treated with NAPP and 15% carbamide peroxide (CP), which contains 5.4% H2O2, and group 3 was treated with 15% CP without NAPP. Color change (ΔE) was measured using the Shade Eye NCC colorimeter. Animals were euthanized one day later to analyze the histological responses occurring in oral soft tissues, including pulp, gingiva, tongue, buccal mucosa, and hard and soft palates. Changes in all samples were analyzed by hematoxylin and eosin staining and Masson’s trichrome. Teeth treated with plasma showed higher ΔE than that obtained with bleaching agents alone. Overall, the histological characteristics observed no appreciable changes. The combinational treatment of plasma had not indicated inflammatory responses as well as thermal damages. NAPP did not cause histological damage in oral soft tissues during tooth bleaching. We suggest that NAPP could be a novel alternative energy source to conventional light sources for tooth bleaching.

scholarly journals New Tricks for an Old (Hedge)Hog: Sonic Hedgehog Regulation of Astrocyte Function

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1353
Author(s):  
A. Denise R. Garcia
Keyword(s):  
Signaling Pathway ◽  
Sonic Hedgehog ◽  
Synapse Formation ◽  
Inflammatory Responses ◽  
Molecular Signaling ◽  
Synaptic Organization ◽  
Shh Signaling ◽  
Broad Array ◽  
And Function ◽  
Molecular Signaling Pathway

The Sonic hedgehog (Shh) molecular signaling pathway is well established as a key regulator of neurodevelopment. It regulates diverse cellular behaviors, and its functions vary with respect to cell type, region, and developmental stage, reflecting the incredible pleiotropy of this molecular signaling pathway. Although it is best understood for its roles in development, Shh signaling persists into adulthood and is emerging as an important regulator of astrocyte function. Astrocytes play central roles in a broad array of nervous system functions, including synapse formation and function as well as coordination and orchestration of CNS inflammatory responses in pathological states. Neurons are the source of Shh in the adult, suggesting that Shh signaling mediates neuron–astrocyte communication, a novel role for this multifaceted pathway. Multiple roles for Shh signaling in astrocytes are increasingly being identified, including regulation of astrocyte identity, modulation of synaptic organization, and limitation of inflammation. This review discusses these novel roles for Shh signaling in regulating diverse astrocyte functions in the healthy brain and in pathology.

scholarly journals Patient with Recurrent Glioblastoma Responding Favorably to Ketogenic Diet Combined with Intranasal Delivery of Perillyl Alcohol: A Case Report and Literature Review

2017 ◽  
Vol 36 (03) ◽  
pp. 194-199 ◽  
Author(s):  
Juliana Santos ◽  
Wanise Cruz ◽  
Axel Schönthal ◽  
Marcela Salazar ◽  
Cristina Fontes ◽  
...  
Keyword(s):  
Ketogenic Diet ◽  
Ketone Bodies ◽  
Methylation Status ◽  
Perillyl Alcohol ◽  
Recurrent Glioblastoma ◽  
Intranasal Delivery ◽  
Reduced Body ◽  
Reduced Frequency ◽  
Methylguanine Methyltransferase ◽  
Magnetic Resonance Imaging Mri

Introduction Monoterpene perillyl alcohol (POH) is cytotoxic to temozolomide-resistant glioma cells, regardless of its O6-methylguanine-methyltransferase (MGMT) promoter methylation status. Moreover, adherence to a ketogenic diet (KD) produced successful outcomes in preclinical and clinical studies in the glioma setting. Case Presentation A 54-year-old Caucasian man had a confirmed diagnosis of refractory glioblastoma multiforme (GBM). The immunohistochemical evaluation was negative for methylation, and failed to detect mutations in the isocitrate dehydrogenase (IDH) 1 and 2 genes. In January 2016, the patient was enrolled in a clinical trial combining daily intranasal delivery of POH in combination with a KD. The KD was administered concomitantly with inhalation of POH (55 mg, 4 times a day) in an uninterrupted administration schedule for 3 months. Results The combination treatment was well-tolerated. The nutritional status and anthropometric measurements of the patient were measured. Adherence to the KD was confirmed by measuring the levels of ketone bodies in the urine. Throughout the treatment, a reduced frequency of seizures was observed. After three months of adherence to the treatment, the patient presented with weight loss, reduced body fat, increased water retention, and a slight increase in bone and muscle mass. A follow-up magnetic resonance imaging (MRI) scan after 3 months of treatment revealed marked reduction of the enhancing lesion. Conclusion Intranasal delivery of POH combined with concomitant adherence to a KD appeared to have a beneficial therapeutic effect in a patient with recurrent GBM. Further studies are needed to evaluate the efficacy of this therapeutic strategy in a larger cohort of treatment-refractory GBM patients.

scholarly journals Ketone Bodies as a Possible Adjuvant to Ketogenic Diet in PDHc Deficiency but Not in GLUT1 Deficiency

2017 ◽  
pp. 53-59 ◽  
Author(s):  
F. Habarou ◽  
N. Bahi-Buisson ◽  
E. Lebigot ◽  
C. Pontoizeau ◽  
M. T. Abi-Warde ◽  
...  
Keyword(s):  
Ketogenic Diet ◽  
Ketone Bodies ◽  
Glut1 Deficiency

scholarly journals Glioblastoma Utilizes Fatty Acids and Ketone Bodies for Growth Allowing Progression during Ketogenic Diet Therapy

iScience ◽  
2020 ◽  
Vol 23 (9) ◽  
pp. 101453
Author(s):  
Jantzen Sperry ◽  
Michael C. Condro ◽  
Lea Guo ◽  
Daniel Braas ◽  
Nathan Vanderveer-Harris ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Ketogenic Diet ◽  
Ketone Bodies ◽  
Diet Therapy

scholarly journals Satiating Effect of a Ketogenic Diet and Its Impact on Muscle Improvement and Oxidation State in Multiple Sclerosis Patients

Nutrients ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 1156 ◽  
Author(s):  
María Benlloch ◽  
María Mar López-Rodríguez ◽  
María Cuerda-Ballester ◽  
Eraci Drehmer ◽  
Sandra Carrera ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Body Composition ◽  
Ketogenic Diet ◽  
Oxidation State ◽  
Lean Mass ◽  
Ketone Bodies ◽  
Paraoxonase 1 ◽  
Before And After ◽  
Multiple Sclerosis Patients ◽  
Beta Hydroxybutyrate

Background: It was previously established that Multiple sclerosis (MS) generates energy alterations at the mitochondrial level related to the loss of muscle mass. Ketone bodies, mainly beta-hydroxybutyrate (BHB), re-establish this energy alteration causing satiety, changes in body composition and a decrease in hormone-dependant hunger, such as ghrelin. The aim of this study was to establish possible improvements in body composition and the level of oxidation in patients with MS, by means of the satiating effect of a ketogenic diet. Methods: A pilot study was carried out with 27 MS patients who were given a Mediterranean isocaloric and ketogenic diet for 4 months. Anthropometric measurements, as well as satiety and hunger perception (VAS scale), were taken. In addition, BHB and paraoxonase 1 (PON1), as an oxidation marker, were measured by spectrophotometric automated assays, and ghrelin was determined by an enzyme immunoassay in the serum. All measurements were taken before and after the intervention. Results: A significant increase in satiety perception at lunch and dinner and of BHB in the blood was obtained. Hunger perception decreased significantly at lunch and dinner with similar levels of ghrelin. In addition, an important increase in lean mass and PON1 was observed. To our knowledge, this is the first study addressing improvements in body composition, oxidation state and metabolism in MS patients, based on the satiating effect of a Mediterranean isocaloric diet. Conclusion: A ketogenic diet increases lean mass and decreases inflammation and oxidation possibly as a consequence of an increase in satiety and decrease in hunger in MS patients.

Ketogenic Diet, Aging, and Neurodegeneration

2016 ◽  
Author(s):  
Kui Xu ◽  
Joseph C. LaManna ◽  
Michelle A. Puchowicz
Keyword(s):  
Oxidative Stress ◽  
Energy Source ◽  
Blood Flow ◽  
Ketogenic Diet ◽  
Ketone Bodies ◽  
Neurovascular Unit ◽  
Cerebral Metabolic Rate ◽  
Downstream Effects ◽  
Atp Supply ◽  
The Brain

The brain is normally completely dependent on glucose, but is capable of using ketones as an alternate energy source, as occurs with prolonged starvation or chronic feeding of a ketogenic diet. Research has shown that ketosis is neuroprotective against ischemic insults in rodents. This review focuses on investigating the mechanistic links to neuroprotection by ketosis in the aged. Recovery from stroke and other pathophysiological conditions in the aged is challenging. Cerebral metabolic rate for glucose, cerebral blood flow, and the defenses against oxidative stress are known to decline with age, suggesting dysfunction of the neurovascular unit. One mechanism of neuroprotection by ketosis involves succinate-induced stabilization of hypoxic inducible factor-1alpha (HIF1α‎) and its downstream effects on intermediary metabolism. The chapter hypothesizes that ketone bodies play a role in the restoration of energy balance (stabilization of ATP supply) and act as signaling molecules through the up-regulation of salvation pathways targeted by HIF1α‎.

Exploiting metabolic susceptibilities in glioblastoma via glycolytic inhibition and ketogenic therapy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13558-e13558
Author(s):  
Frederic Anthony Vallejo ◽  
Sumedh Shah ◽  
Winston Walters ◽  
Katrina Kostenko ◽  
Ingrid Torrens ◽  
...  
Keyword(s):  
Stem Cell ◽  
Western Blot ◽  
Ketogenic Diet ◽  
Ketone Bodies ◽  
Combined Treatment ◽  
Glycolytic Enzymes ◽  
Parp Cleavage ◽  
Low Carbohydrate Diet ◽  
Dose Dependent Decrease ◽  
Dose Dependent

e13558 Background: Glioblastoma (GBM) remains one of the most lethal primary brain tumors in children and adults. Despite enormous efforts to elucidate the genetic and epigenetic drivers of this disease, the prognosis for patients diagnosed with GBM remains dismal. Because tumor cell metabolism differs greatly from that of normal non-cancerous cells, it is possible to develop therapies which more effectively target the cancer cell while sparing normal cells. Growing in popularity is the ketogenic diet, which is a high fat, very low carbohydrate diet resulting in the production of ketone bodies, acetoacetate (AA) and β-hydroxybutyrate (βHB) to generate ATP. Methods: Analysis conducted by open-access GBM patient database, mts assay, Western blot, neurosphere assay, and TEM. Results: Enzymes required for ketone metabolism (BDH1 and OXCT1) were significantly downregulated in GBM while glycolytic enzymes were significantly upregulated (HK2, HK1, SLC2A3, NAMPT, G6PD). GBM stem cell (GSC) markers (CD44, STAT3) positively correlated with glycolytic enzymes. Ultrastructural analysis of GSCs indicated that about half of the mitochondria were missing cristae, highly suggestive of an increased glycolytic dependency. Treatment of patient-derived GSC lines as well as non-stem cell lines SJGBM2 (pediatric) and U87 (adult) resulted in a dose-dependent decrease in viability in response to the glycolytic inhibitor 2-deoxy-D-glucose (2-DG). When cells were exposed to ketone bodies, AA but not βHB induced a dose-dependent decrease in cell viability with 10 mM reducing viability ranging from 20-80% of non-treated controls. Western blot analysis demonstrated robust caspase activation and PARP cleavage in response to AA. Furthermore, AA significantly reduced GSC neurosphere formation at 2.5 mM suggesting inhibition of GSC self-renewal pathways. Combined treatment of low dose 2-DG (50 μM) with increasing concentrations of AA resulted in more cell death than either treatment. The effect was more than additive at the low concentrations of AA (1- 5 mM) suggesting synergy. Conclusions: Glycolytic inhibition in conjunction with the ketogenic diet may be a promising therapeutic route for this difficult-to-treat cancer.

scholarly journals The efficacy of a ketogenic diet in preclinical models of IDH wild-type and IDH mutant glioma

2021 ◽  
Author(s):  
Rodrigo Javier ◽  
Wenxia Wang ◽  
Michael Drumm ◽  
Kathleen McCortney ◽  
Jann N. Sarkaria ◽  
...  
Keyword(s):  
Ketogenic Diet ◽  
Sleeping Beauty ◽  
Standard Diet ◽  
Wild Type ◽  
Preclinical Models ◽  
Isocitrate Dehydrogenase 1 ◽  
Low Carbohydrate ◽  
Cellular Biochemistry

ABSTRACTInfiltrative gliomas are the most common neoplasms arising in the brain, and remain largely incurable despite decades of research. A subset of these gliomas contains mutations in isocitrate dehydrogenase 1 (IDH1) or, less commonly, IDH2 (together called “IDHmut”). These mutations alter cellular biochemistry, and IDHmut gliomas are generally less aggressive than IDH wild-type (IDHwt) gliomas. Some preclinical studies and clinical trials have suggested that a ketogenic diet (KD), characterized by low-carbohydrate and high-fat content, may be beneficial in slowing glioma progression. However, not all studies have shown promising results, and to date, no study has addressed whether IDHmut gliomas might be more sensitive to KD. The aim of the current study was to compare the effects of KD in preclinical models of IDHwt versus IDHmut gliomas. In vitro, simulating KD by treatment with the ketone body β-hydroxybutyrate had no effect on the proliferation of patient-derived IDHwt or IDHmut glioma cells. Likewise, a cycling KD, wherein mice alternated between KD and a standard diet (SD), had no effect on the in vivo growth of patient-derived IDHwt or IDHmut gliomas, even though the cycling KD did result in persistently elevated circulating ketones. Furthermore, KD conferred no survival benefit in mice engrafted with Sleeping-Beauty transposase-engineered IDHmut glioma. These data suggest that neither IDHwt nor IDHmut gliomas are particularly responsive to KD.

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