Ketone Body, 3-Hydroxybutyrate: Minor Metabolite - Major Medical Manifestations

2020 ◽  
Vol 105 (9) ◽  
pp. 2884-2892 ◽  
Author(s):  
Niels Møller
Keyword(s):  
Ketone Body ◽  
Ketone Bodies ◽  
Muscle Protein ◽  
Neurological Diseases ◽  
Receptor Protein ◽  
Ketogenic Diets ◽  
Patients With Diabetes ◽  
Long Time ◽  
Free Fatty Acid Receptors ◽  
The Moment

Abstract Ketone bodies – 3-hydroxybutyrate (3-OHB), acetoacetate, and acetone – are ancient, evolutionarily preserved, small fuel substrates, which uniquely can substitute and alternate with glucose under conditions of fuel and food deficiency. Once canonized as a noxious, toxic pathogen leading to ketoacidosis in patients with diabetes, it is now becoming increasingly clear that 3-OHB possesses a large number of beneficial, life-preserving effects in the fields of clinical science and medicine. 3-OHB, the most prominent ketone body, binds to specific hydroxyl-carboxylic acid receptors and inhibits histone deacetylase enzymes, free fatty acid receptors, and the NOD-like receptor protein 3 inflammasome, tentatively inhibiting lipolysis, inflammation, oxidative stress, cancer growth, angiogenesis, and atherosclerosis, and perhaps contributing to the increased longevity associated with exercise and caloric restriction. Clinically ketone bodies/ketogenic diets have for a long time been used to reduce the incidence of seizures in epilepsy and may have a role in the treatment of other neurological diseases such as dementia. 3-OHB also acts to preserve muscle protein during systemic inflammation and is an important component of the metabolic defense against insulin-induced hypoglycemia. Most recently, a number of studies have reported that 3-OHB dramatically increases myocardial blood flow and cardiac output in control subjects and patients with heart failure. At the moment, scientific interest in ketone bodies, in particular 3-OHB, is in a hectic transit and, hopefully, future, much needed, controlled clinical studies will reveal and determine to which extent the diverse biological manifestations of 3-OHB should be introduced medically.

scholarly journals Ketone Body Metabolism in the Ischemic Heart

2021 ◽  
Vol 8 ◽  
Author(s):  
Stephen C. Kolwicz
Keyword(s):  
Ketone Body ◽  
Ketone Bodies ◽  
Ischemia Reperfusion ◽  
Ischemic Heart ◽  
Myocardial Infarctions ◽  
Ketogenic Diets ◽  
Health And Disease ◽  
Ketone Body Metabolism ◽  
Artery Disease ◽  
Fuel Source

Ketone bodies have been identified as an important, alternative fuel source in heart failure. In addition, the use of ketone bodies as a fuel source has been suggested to be a potential ergogenic aid for endurance exercise performance. These findings have certainly renewed interest in the use of ketogenic diets and exogenous supplementation in an effort to improve overall health and disease. However, given the prevalence of ischemic heart disease and myocardial infarctions, these strategies may not be ideal for individuals with coronary artery disease. Although research studies have clearly defined changes in fatty acid and glucose metabolism during ischemia and reperfusion, the role of ketone body metabolism in the ischemic and reperfused myocardium is less clear. This review will provide an overview of ketone body metabolism, including the induction of ketosis via physiological or nutritional strategies. In addition, the contribution of ketone body metabolism in healthy and diseased states, with a particular emphasis on ischemia-reperfusion (I-R) injury will be discussed.

scholarly journals Diabetic nephropathy: Pathogenesis and treatment

1996 ◽  
Vol 42 (4) ◽  
pp. 37-42
Author(s):  
A. V. Vorontsov ◽  
M. V. Shestakova
Keyword(s):  
Diabetic Nephropathy ◽  
Type I Diabetes ◽  
Clinical Manifestations ◽  
Type I ◽  
Clinical Methods ◽  
Patients With Diabetes ◽  
Long Time ◽  
Modern Classification ◽  
Insulin Dependent ◽  
The Moment

Currently, diabetic nephropathy (DN) is the leading cause of disability and mortality in patients with diabetes mellitus (DM). Developing in 4045% of patients, both insulin-dependent IDDM (type I) and non-insulin-dependent IDDM (type II) diabetes, this formidable complication leads to the development of chronic renal failure, and ultimately to the death of patients from uremia. The first kidney damage in diabetes was described by R. Kimmelstiel and C. Wilson in 1936. It is clinically characterized by the following manifestations: increasing proteinuria (with unchanged urinary sediment), hypertension, the formation of nephrotic syndrome (in about 30% of patients) and a progressive decrease in filtration kidney function. The insidiousness of this complication of diabetes lies in the fact that it develops gradually and remains unnoticed for a long time, since at the initial stages the patient does not cause discomfort. And in the later stages, when the presence of DN is no longer in doubt, preventing its further progression is extremely difficult, and often impossible. For many years in our country, the classification of DNs was used by V. R. Klyachko, according to which prenephrotic, nephrotic, and nephrosclerotic stages were distinguished. According to this classification, DN is diagnosed only from the moment when the patient develops proteinuria, registered by conventional laboratory methods, which indicates the severity and irreversibility of pathological changes in the kidneys. The modern classification, distinguishing stages at which clinical manifestations are still absent, and only functional disorders are detected, was proposed by S. Mogensen in 1983 (see table). In accordance with this classification, the first 3 stages are not detected by conventional clinical methods (preclinical stage of DN). The most informative marker of the early stages of DN is the determination of microalbuminuria (MAU), which means the excretion of albumin with urine in an amount of 30 to 300 mg / day. Identification of UIA in a patient with type I diabetes means that the probability of developing a clinical picture of DN in his next 10 years is 80%.

scholarly journals Ketogenic Diets and Exercise Performance

Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2296 ◽  
Author(s):  
Kristin L. Harvey ◽  
Lola E. Holcomb ◽  
Stephen C. Kolwicz
Keyword(s):  
Exercise Performance ◽  
Cardiac Dysfunction ◽  
Ketone Body ◽  
Ketone Bodies ◽  
Scientific Evidence ◽  
Blood Lipid ◽  
Potential Method ◽  
Mainstream Media ◽  
Ketogenic Diets ◽  
Ketone Body Metabolism

The ketogenic diet (KD) has gained a resurgence in popularity due to its purported reputation for fighting obesity. The KD has also acquired attention as an alternative and/or supplemental method for producing energy in the form of ketone bodies. Recent scientific evidence highlights the KD as a promising strategy to treat obesity, diabetes, and cardiac dysfunction. In addition, studies support ketone body supplements as a potential method to induce ketosis and supply sustainable fuel sources to promote exercise performance. Despite the acceptance in the mainstream media, the KD remains controversial in the medical and scientific communities. Research suggests that the KD or ketone body supplementation may result in unexpected side effects, including altered blood lipid profiles, abnormal glucose homeostasis, increased adiposity, fatigue, and gastrointestinal distress. The purpose of this review article is to provide an overview of ketone body metabolism and a background on the KD and ketone body supplements in the context of obesity and exercise performance. The effectiveness of these dietary or supplementation strategies as a therapy for weight loss or as an ergogenic aid will be discussed. In addition, the recent evidence that indicates ketone body metabolism is a potential target for cardiac dysfunction will be reviewed.

scholarly journals Ketogenic diets inhibit mitochondrial biogenesis and induce cardiac fibrosis

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Sha Xu ◽  
Hui Tao ◽  
Wei Cao ◽  
Li Cao ◽  
Yan Lin ◽  
...  
Keyword(s):  
Mitochondrial Biogenesis ◽  
Ketone Body ◽  
Cardiac Fibrosis ◽  
Cardiomyocyte Apoptosis ◽  
Healthy Individuals ◽  
Cell Respiration ◽  
Ketogenic Diets ◽  
Mitochondrial Ribosome ◽  
Encoding Genes ◽  
Human Atrial Fibrillation

AbstractIn addition to their use in relieving the symptoms of various diseases, ketogenic diets (KDs) have also been adopted by healthy individuals to prevent being overweight. Herein, we reported that prolonged KD exposure induced cardiac fibrosis. In rats, KD or frequent deep fasting decreased mitochondrial biogenesis, reduced cell respiration, and increased cardiomyocyte apoptosis and cardiac fibrosis. Mechanistically, increased levels of the ketone body β-hydroxybutyrate (β-OHB), an HDAC2 inhibitor, promoted histone acetylation of the Sirt7 promoter and activated Sirt7 transcription. This in turn inhibited the transcription of mitochondrial ribosome-encoding genes and mitochondrial biogenesis, leading to cardiomyocyte apoptosis and cardiac fibrosis. Exogenous β-OHB administration mimicked the effects of a KD in rats. Notably, increased β-OHB levels and SIRT7 expression, decreased mitochondrial biogenesis, and increased cardiac fibrosis were detected in human atrial fibrillation heart tissues. Our results highlighted the unknown detrimental effects of KDs and provided insights into strategies for preventing cardiac fibrosis in patients for whom KDs are medically necessary.

scholarly journals Ketone body 3-hydroxybutyrate as a biomarker of aggression

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
A. M. Whipp ◽  
E. Vuoksimaa ◽  
T. Korhonen ◽  
R. Pool ◽  
A. But ◽  
...  
Keyword(s):  
Young Adults ◽  
Ketone Body ◽  
Ketone Bodies ◽  
Population Based ◽  
Resonance Spectroscopy ◽  
Linear Regression Models ◽  
Complex Behaviour ◽  
Replication Sample ◽  
Discovery Sample ◽  
Independent Replication

AbstractHuman aggression is a complex behaviour, the biological underpinnings of which remain poorly known. To gain insights into aggression biology, we studied relationships with aggression of 11 low-molecular-weight metabolites (amino acids, ketone bodies), processed using 1H nuclear magnetic resonance spectroscopy. We used a discovery sample of young adults and an independent adult replication sample. We studied 725 young adults from a population-based Finnish twin cohort born 1983–1987, with aggression levels rated in adolescence (ages 12, 14, 17) by multiple raters and blood plasma samples at age 22. Linear regression models specified metabolites as the response variable and aggression ratings as predictor variables, and included several potential confounders. All metabolites showed low correlations with aggression, with only one—3-hydroxybutyrate, a ketone body produced during fasting—showing significant (negative) associations with aggression. Effect sizes for different raters were generally similar in magnitude, while teacher-rated (age 12) and self-rated (age 14) aggression were both significant predictors of 3-hydroxybutyrate in multi-rater models. In an independent replication sample of 960 adults from the Netherlands Twin Register, higher aggression (self-rated) was also related to lower levels of 3-hydroxybutyrate. These exploratory epidemiologic results warrant further studies on the role of ketone metabolism in aggression.

scholarly journals Low-Carb and Ketogenic Diets in Type 1 and Type 2 Diabetes

Nutrients ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 962 ◽  
Author(s):  
Bolla ◽  
Caretto ◽  
Laurenzi ◽  
Scavini ◽  
Piemonti
Keyword(s):  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Dietary Interventions ◽  
Ketogenic Diets ◽  
Patients With Diabetes ◽  
Intrinsic Complexity ◽  
Few Data ◽  
Reducing Carbohydrates

Low-carb and ketogenic diets are popular among clinicians and patients, but the appropriateness of reducing carbohydrates intake in obese patients and in patients with diabetes is still debated. Studies in the literature are indeed controversial, possibly because these diets are generally poorly defined; this, together with the intrinsic complexity of dietary interventions, makes it difficult to compare results from different studies. Despite the evidence that reducing carbohydrates intake lowers body weight and, in patients with type 2 diabetes, improves glucose control, few data are available about sustainability, safety and efficacy in the long-term. In this review we explored the possible role of low-carb and ketogenic diets in the pathogenesis and management of type 2 diabetes and obesity. Furthermore, we also reviewed evidence of carbohydrates restriction in both pathogenesis of type 1 diabetes, through gut microbiota modification, and treatment of type 1 diabetes, addressing the legitimate concerns about the use of such diets in patients who are ketosis-prone and often have not completed their growth.

scholarly journals Effects of 3-hydroxybutyrate and free fatty acids on muscle protein kinetics and signaling during LPS-induced inflammation in humans: anticatabolic impact of ketone bodies

2018 ◽  
Vol 108 (4) ◽  
pp. 857-867 ◽  
Author(s):  
Henrik H Thomsen ◽  
Nikolaj Rittig ◽  
Mogens Johannsen ◽  
Andreas B Møller ◽  
Jens Otto Jørgensen ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Free Fatty Acids ◽  
Acute Inflammation ◽  
Ketone Bodies ◽  
Muscle Protein ◽  
Initiation Factor ◽  
Whole Body ◽  
Protein Breakdown ◽  
Protein Kinetics ◽  
Nonesterified Fatty Acids

Abstract Background Acute inflammation, and subsequent release of bacterial products (e.g. LPS), inflammatory cytokines, and stress hormones, is catabolic, and the loss of lean body mass predicts morbidity and mortality. Lipid intermediates may reduce protein loss, but the roles of free fatty acids (FFAs) and ketone bodies during acute inflammation are unclear. Objective We aimed to test whether infusions of 3-hydroxybutyrate (3OHB), FFAs, and saline reduce protein catabolism during exposure to LPS and Acipimox (to restrict and control endogenous lipolysis). Design A total of 10 healthy male subjects were randomly tested 3 times, with: 1) LPS, Acipimox (Olbetam) and saline, 2) LPS, Acipimox, and nonesterified fatty acids (Intralipid), and 3) LPS, Acipimox, and 3OHB, during a 5-h basal period and a 2-h hyperinsulinemic, euglycemic clamp. Labeled phenylalanine, tyrosine, and urea tracers were used to estimate protein kinetics, and muscle biopsies were taken for Western blot analysis of protein metabolic signaling. Results 3OHB infusion increased 3OHB concentrations (P < 0.0005) to 3.5 mM and decreased whole-body phenylalanine-to-tyrosine degradation. Basal and insulin-stimulated net forearm phenylalanine release decreased by >70% (P < 0.005), with both appearance and phenylalanine disappearance being profoundly decreased. Phosphorylation of eukaryotic initiation factor 2α at Ser51 was increased in skeletal muscle, and S6 kinase phosphorylation at Ser235/236 tended (P = 0.074) to be decreased with 3OHB infusion (suggesting inhibition of protein synthesis), whereas no detectable effects were seen on markers of protein breakdown. Lipid infusion did not affect phenylalanine kinetics, and insulin sensitivity was unaffected by interventions. Conclusion During acute inflammation, 3OHB has potent anticatabolic actions in muscle and at the whole-body level; in muscle, reduction of protein breakdown overrides inhibition of synthesis. This trial was registered at clinicaltrials.gov as NCT01752348.

Overload-induced androgen receptor expression in the aged rat hindlimb receiving nandrolone decanoate

2003 ◽  
Vol 94 (3) ◽  
pp. 1153-1161 ◽  
Author(s):  
Won Jun Lee ◽  
Joseph McClung ◽  
G. A. Hand ◽  
James A. Carson
Keyword(s):  
Androgen Receptor ◽  
Muscle Mass ◽  
Protein Concentration ◽  
Muscle Protein ◽  
Receptor Expression ◽  
Receptor Protein ◽  
Nandrolone Decanoate ◽  
Muscle Weight ◽  
Aged Rat ◽  
Androgen Receptor Protein

This study's purpose was to examine whether functional overload with nandrolone decanoate (ND) administration increased muscle mass and steroid receptor concentration in aged rat soleus (Sol) and plantaris (Plan) muscle. ND (6 mg/kg body wt) was administered once a week for 4 wk, whereas control rats received sesame seed oil injections. Functional overload of the hindlimb Sol and Plan was induced by synergistic gastrocnemius muscle ablation at the beginning of the fourth week. Adult (5 mo of age) and aged rats (25 mo of age) were randomly assigned to four groups: control, overload, control-ND, and overload-ND. Seven days of functional overload increased adult Sol muscle mass 27%, whereas the aged Sol muscle mass did not change. The aged overloaded Sol muscle receiving ND significantly increased muscle weight by 35% and total muscle protein by 24%. Aged Plan muscle did not increase muscle weight with overload or ND treatment. Androgen receptor protein was induced by ND treatment and functional Ov, and combining the two treatments induced Sol androgen receptor protein concentration above either alone. Sol glucocorticoid receptor protein concentration increased in overload groups of both ages. ND administration can increase aged Sol muscle mass and protein content after 7 days of functional overload, and the cooperative induction of androgen receptor may be important for this response.

scholarly journals Gluconeogenesis in the cow. The effects of a glucocorticoid on hepatic intermediary metabolism

1970 ◽  
Vol 116 (5) ◽  
pp. 865-874 ◽  
Author(s):  
G. D. Baird ◽  
R. J. Heitzman
Keyword(s):  
Blood Glucose ◽  
Ketone Body ◽  
Ketone Bodies ◽  
Tyrosine Aminotransferase ◽  
Aspartate Transaminase ◽  
Blood Concentrations ◽  
Lactating Cows ◽  
Glycolytic Intermediates ◽  
Blood Glucose Concentrations ◽  
Parallel Measurements

1. The hepatic concentrations of the ketone bodies and of metabolites and activities of enzymes involved in gluconeogenesis were measured in healthy lactating and non-lactating cows 48h after administration of Voren, an ester of dexamethasone, and compared with those found in control animals given saline. Parallel measurements were also made of the blood concentrations of several of the metabolites. 2. Blood glucose concentrations were raised in the Voren-treated animals, whereas blood ketone body and free fatty acid concentrations were unaltered. Similarly there was no change in the hepatic concentrations of the ketone bodies. 3. Significant increases were found in the hepatic concentrations of citrate, 2-oxo-glutarate and malate in both groups of animals given Voren. 4. The hepatic concentrations of those glycolytic intermediates that were measured either decreased or did not change after Voren treatment. 5. The enzymes aspartate transaminase and fructose 1,6-diphosphatase were unchanged in activity after Voren administration, whereas phosphopyruvate carboxylase (EC 4.1.1.32) activity was depressed in the lactating group. However, glucose 6-phosphatase, tryptophan oxygenase and tyrosine aminotransferase increased in activity. 6. In several cases those hepatic metabolites that increased in concentration after Voren administration were present in lower concentration in normal lactating cows than in normal non-lactating cows. The same applied mutatis mutandis to those metabolites that were decreased by Voren. 7. These findings are discussed in relation to the use of glucocorticoids in the treatment of bovine ketosis.

scholarly journals Exogenous Ketone Bodies as Promising Neuroprotective Agents for Developmental Brain Injury

2018 ◽  
Vol 40 (5-6) ◽  
pp. 451-462 ◽  
Author(s):  
Thomas R. Wood ◽  
Brianna J. Stubbs ◽  
Sandra E. Juul
Keyword(s):  
Brain Injury ◽  
Ketone Bodies ◽  
Adult Brain ◽  
Metabolic Energy ◽  
Human Infant ◽  
Neuroprotective Effects ◽  
Ketogenic Diets ◽  
Promising Area ◽  
Fetus And Neonate ◽  
Uptake And Metabolism

Ketone bodies are a promising area of neuroprotection research that may be ideally suited to the injured newborn. During normal development, the human infant is in significant ketosis for at least the first week of life. Ketone uptake and metabolism is upregulated in the both the fetus and neonate, with ketone bodies providing at least 10% of cerebral metabolic energy requirements, as well as being the preferred precursors for the synthesis of fatty acids and cholesterol. At the same time, ketone bodies have been shown to have multiple neuroprotective effects, including being anticonvulsant, decreasing oxidative stress and inflammation, and epigenetically upregulating the production of neurotrophic factors. While ketogenic diets and exogenous ketosis are largely being investigated in the setting of adult brain injury, the adaptation of the neonate to ketosis suggests that developmental brain injury may be the area most suited to the use of ketones for neuroprotection. Here, we describe the mechanisms by which ketone bodies exert their neuroprotective effects, and how these may translate to benefits within each of the phases of neonatal asphyxial brain injury.

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