Ketone bodies: from enemy to friend and guardian angel

BMC Medicine, Journal Year: 2021, Volume and Issue: 19(1)

Published: Dec. 9, 2021

Abstract During starvation, fasting, or a diet containing little digestible carbohydrates, the circulating insulin levels are decreased. This promotes lipolysis, and breakdown of fat becomes major source energy. The hepatic energy metabolism is regulated so that under these circumstances, ketone bodies generated from β-oxidation fatty acids secreted as ancillary fuel, in addition to gluconeogenesis. Increased plasma thus indicate dietary shortage carbohydrates. Ketone not only serve fuel but also promote resistance oxidative inflammatory stress, there decrease anabolic insulin-dependent expenditure. It has been suggested beneficial non-metabolic actions on organ functions mediated by them acting ligand specific cellular targets. We propose here role different pathway initiated induction stress mitochondria during increased ketolysis. Oxidative induced body long term because it initiates an adaptive (hormetic) response characterized activation master regulators cell-protective mechanism, nuclear factor erythroid 2-related 2 (Nrf2), sirtuins, AMP-activated kinase. results resolving upregulation anti-oxidative anti-inflammatory activities, improved mitochondrial function growth, DNA repair, autophagy. In heart, enhanced ketolysis improves damage after ischemic insults cardiotoxic doxorubicin. Sodium-dependent glucose co-transporter (SGLT2) inhibitors may exert their cardioprotective action via increasing conclude synthesis use periods deficient food supply low causes latter protective which allows cells cope with lower availability. Keywords Ketogenic diet, bodies, Beta hydroxybutyrate, Insulin, Obesity, Type diabetes, Inflammation, Cardiovascular disease, SGLT2, Hormesis

Language: Английский

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The Potential Role of Gut Microbiota in Alzheimer’s Disease: From Diagnosis to Treatment

Nutrients, Journal Year: 2022, Volume and Issue: 14(3), P. 668 - 668

Published: Feb. 5, 2022

Gut microbiota is emerging as a key regulator of many disease conditions and its dysregulation implicated in the pathogenesis several gastrointestinal extraintestinal disorders. More recently, gut microbiome alterations have been linked to neurodegeneration through increasingly defined brain axis, opening possibility for new microbiota-based therapeutic options. Although studies conducted unravel possible relationship between Alzheimer’s Disease (AD) progression, diagnostic potential approaches aiming at restoring eubiosis remain be fully addressed. In this narrative review, we briefly summarize role homeostasis health disease, present evidence AD patients. Based on these observations, then discuss how dysbiosis might exploited tool early advanced stages, examine prebiotics, probiotics, fecal transplantation, diets complementary interventions thus offering insights into diagnosis treatment devastating progressive disease.

Language: Английский

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The Role of Ketogenic Diet in the Treatment of Neurological Diseases

Nutrients, Journal Year: 2022, Volume and Issue: 14(23), P. 5003 - 5003

Published: Nov. 24, 2022

Over a hundred years of study on the favourable effect ketogenic diets in treatment epilepsy have contributed to long-lasting discussion its potential influence other neurological diseases. A significant increase number scientific studies that field has been currently observed. The aim this paper is widespread, thorough analysis available evidence respect role diet therapy diseases such as: epilepsy, Alzheimer’s disease (AD), Parkinson’s (PD), multiple sclerosis (MS) and migraine. wide range mechanisms action demonstrated diseases, including, among effects, reduction inflammatory conditions amount reactive oxygen species (ROS), restoration myelin sheath neurons, formation regeneration mitochondria, neuronal metabolism, provision an alternative source energy for neurons (ketone bodies), glucose insulin concentrations, amyloid plaques, induction autophagy, alleviation microglia activation, excessive modulation intestinal microbiota, expression genes, dopamine production glutamine conversion into GABA. discussed (including randomised controlled studies), conducted patients, stressed effectiveness promising therapeutic frequent advantage was over non-ketogenic (in control groups) with simultaneous safety feasibility when conducting nutritional model.

Language: Английский

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The Ketogenic Diet for Refractory Mental Illness: A Retrospective Analysis of 31 Inpatients

Frontiers in Psychiatry, Journal Year: 2022, Volume and Issue: 13

Published: July 6, 2022

Background and Hypothesis The robust evidence base supporting the therapeutic benefit of ketogenic diets in epilepsy other neurological conditions suggests this same metabolic approach may also psychiatric conditions. Study Design In retrospective analysis clinical care, 31 adults with severe, persistent mental illness (major depressive disorder, bipolar schizoaffective disorder) whose symptoms were poorly controlled despite intensive management admitted to a hospital placed on diet restricted maximum 20 grams carbohydrate per day as an adjunct conventional inpatient care. duration intervention ranged from 6 248 days. Results Three patients unable adhere for >14 days excluded final analysis. Among included participants, means standard deviations (SDs) improved Hamilton Depression Rating Scale scores 25.4 (6.3) 7.7 (4.2), P < 0.001 Montgomery-Åsberg 29.6 (7.8) 10.1 (6.5), 0.001. 10 illness, mean (SD) Positive Negative Syndrome (PANSS) 91.4 (15.3) 49.3 (6.9), Significant improvements observed health measures including weight, blood pressure, glucose, triglycerides. Conclusions administration semi-controlled setting treatment-refractory was feasible, well-tolerated, associated significant substantial depression psychosis multiple markers health.

Language: Английский

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Targeting fatty acid metabolism in glioblastoma

Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 133(1)

Published: Jan. 2, 2023

Glioblastoma (GBM) is a primary tumor of the brain defined by its uniform lethality and resistance to conventional therapies. There have been considerable efforts untangle metabolic underpinnings this disease find novel therapeutic avenues for treatment. An emerging focus in field fatty acid (FA) metabolism, which critical numerous diverse biological processes involved GBM pathogenesis. These can be classified into four broad fates: anabolism, catabolism, regulation ferroptosis, generation signaling molecules. Each fate provides unique perspective we inspect biology gives us road map understanding complicated field. This Review discusses basic, translational, clinical insights each these fates provide contemporary FA GBM. It clear, based on literature, that there are far more questions than answers metabolism GBM, substantial should made complex intractable disease.

Language: Английский

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Exercise therapy to prevent and treat Alzheimer’s disease

Frontiers in Aging Neuroscience, Journal Year: 2023, Volume and Issue: 15

Published: Aug. 4, 2023

Alzheimer’s disease (AD) is a progressive neurodegenerative in the elderly with dementia, memory loss, and severe cognitive impairment that imposes high medical costs on individuals. The causes of AD include increased deposition amyloid beta (Aβ) phosphorylated tau, age, mitochondrial defects, neuroinflammation, decreased synaptic connections, nerve growth factors (NGF). While animals moderate-intensity exercise restores hippocampal amygdala through levels p-AKT, p-TrkB, p-PKC Aβ, tau phosphorylation, precursor proteins (APP) AD. Aerobic (with an intensity 50–75% VO2 max) prevents volume reduction, spatial learning reduction increasing flexibility. Exercise training induces binding brain-derived neurotrophic factor (BDNF) to TrkB NGF TrkA induce cell survival neuronal plasticity. After aerobic high-intensity interval training, increase VEGF, angiopoietin 1 2, NO, tPA, HCAR1 cerebral vessels blood flow angiogenesis cerebellum, motor cortex, striatum, hippocampus. In hippocampus, decreases fragmentation, DRP1, FIS1, improving OPA1, MFN1, MFN2, morphology. humans, acute as anti-inflammatory condition IL-6 such IL-1RA IL-10. Moderate-intensity also inhibits inflammatory markers IFN-γ, IL-1β, IL-6, CRP, TNF-α, sTNFR1, COX-2, NF-κB. significantly increases plasma BDNF, factor, plasticity, activity, memory, exploratory behavior subjects. Irisin myokine released from skeletal muscle during protects hippocampus by suppressing Aβ accumulation promoting proliferation STAT3 signaling. Therefore, combined strength balance coordination social activities seems provide important benefits for people

Language: Английский

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Astrocyte metabolism and signaling pathways in the CNS

Frontiers in Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: Sept. 4, 2023

Astrocytes comprise half of the cells in central nervous system and play a critical role maintaining metabolic homeostasis. Metabolic dysfunction astrocytes has been indicated as primary cause neurological diseases, such depression, Alzheimer’s disease, epilepsy. Although functionalities are well known, their relationship to disorders is poorly understood. The ways which regulate metabolism glucose, amino acids, lipids have all implicated diseases. Metabolism also exhibited significant influence on neuron functionality brain’s neuro-network. In this review, we focused processes present astrocytes, most notably glucose pathway, fatty acid amino-acid pathway. For metabolism, glycolysis pentose-phosphate oxidative phosphorylation followed oxidation, ketone body sphingolipid metabolism. summarized neurotransmitter serine kynurenine pathways. This review will provide an overview functional changes astrocyte overall perspective current treatment therapy for disorders.

Language: Английский

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Mitochondrial heterogeneity and adaptations to cellular needs

Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(5), P. 674 - 686

Published: May 1, 2024

Language: Английский

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Dysbiosis and Alzheimer’s Disease: A Role for Chronic Stress?

Biomolecules, Journal Year: 2021, Volume and Issue: 11(5), P. 678 - 678

Published: April 30, 2021

Alzheimer’s disease (AD) is an incurable, neuropsychiatric, pathological condition that deteriorates the worth of geriatric lives. AD characterized by aggregated senile amyloid plaques, neurofibrillary tangles, neuronal loss, gliosis, oxidative stress, neurotransmitter dysfunction, and bioenergetic deficits. The changes in GIT composition harmony have been recognized as a decisive interesting player pathologies including AD. Microbiota control influence oxidoreductase status, inflammation, immune system, endocrine system through which it may impact on cognitive domain. altered malfunctioned state microbiota associated with minor infections to complicated illnesses include psychosis neurodegeneration, several studies show regulates plasticity development. (dysbiosis) affect behavior, stress response, functions. Chronic stress-mediated progression also has well-defined role intermingles at various physiological levels directly impacts advancement stress-modulated alterations well-established markers but gut–brain axis mediation downstream signaling mechanisms modulate microbial commensals GIT. extensive literature reports chronic stressors composition, metabolic activities, capacities. present manuscript aims elucidate mechanistic pathways induces dysbiosis, turn escalates neuropathological cascade stress–dysbiosis appears feasible zone work direction treatment

Language: Английский

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Ketone Bodies in the Brain Beyond Fuel Metabolism: From Excitability to Gene Expression and Cell Signaling

Frontiers in Molecular Neuroscience, Journal Year: 2021, Volume and Issue: 14

Published: Aug. 27, 2021

Ketone bodies are metabolites that replace glucose as the main fuel of brain in situations scarcity, including prolonged fasting, extenuating exercise, or pathological conditions such diabetes. Beyond their role an alternative for brain, impact ketone on neuronal physiology has been highlighted by use so-called “ketogenic diets,” which were proposed about a century ago to treat infantile seizures. These diets mimic fasting reducing drastically intake carbohydrates and proteins replacing them with fat, thus promoting ketogenesis. The fact ketogenic have profound effect epileptic seizures points complex biological effects addition source ATP. In this review, we specifically focus ability regulate excitability gene expression respond oxidative stress. Finally, also discuss capacity signaling molecules cells.

Language: Английский

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