Ketone Body Utilization and Its Metabolic Effect in Resting Muscles of Normal and Streptozotocin-Diabetic Rats.

Okuda, Yukichi; Kawai, Koichi; Ohmori, Hitoshi; Yamashita, Kamejiro

doi:10.1507/endocrj1954.38.245

Cited by 14 publications

(10 citation statements)

References 16 publications

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“…Relatively little is known at the cellular level about SCOT gene and protein expression regulators. Oxct1 mRNA expression and SCOT protein and activity are diminished in ketotic states, possibly through PPAR-dependent mechanisms (Fenselau and Wallis, 1974; Fenselau and Wallis, 1976; Grinblat et al, 1986; Okuda et al, 1991; Turko et al, 2001; Wentz et al, 2010). In diabetic ketoacidosis, the mismatch between hepatic ketogenesis and extrahepatic oxidation becomes exacerbated by impairment of SCOT activity.…”

Section: Regulation Of Hmgcs2 and Scot/oxct1mentioning

confidence: 99%

Multi-dimensional Roles of Ketone Bodies in Fuel Metabolism, Signaling, and Therapeutics

2017

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Ketone body metabolism is a central node in physiological homeostasis. In this review, we discuss how ketones serve discrete fine-tuning metabolic roles that optimize organ and organism performance in varying nutrient states, and protect from inflammation and injury in multiple organ systems. Traditionally viewed as metabolic substrates enlisted only in carbohydrate restriction, recent observations underscore the importance of ketone bodies as vital metabolic and signaling mediators when carbohydrates are abundant. Complementing a repertoire of known therapeutic options for diseases of the nervous system, prospective roles for ketone bodies in cancer have arisen, as have intriguing protective roles in heart and liver, opening therapeutic options in obesity-related and cardiovascular disease. Controversies in ketone metabolism and signaling are discussed to reconcile classical dogma with contemporary observations.

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Section: Regulation Of Hmgcs2 and Scot/oxct1mentioning

confidence: 99%

Multi-dimensional Roles of Ketone Bodies in Fuel Metabolism, Signaling, and Therapeutics

2017

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“…Relative to ketogenesis, little is known about the regulation of mediators of ketone body oxidation. Perhaps paradoxically, expression of the gene encoding CoA transferase (Oxct1), CoA transferase protein abundance, and CoA transferase enzymatic activity are all diminished in rodent heart and muscle during states of sustained ketosis (53,54,71,152,213,228). In pathological contexts such as diabetic ketoacidosis, diminution of CoA transferase abundance and activity limit ketone body disposal, whereas insulin deficiency (or severe impairment of its signaling) stimulates peripheral fatty acid mobilization and unabated hepatic ketogenesis.…”

Section: Ketone Body Metabolismmentioning

confidence: 99%

Ketone body metabolism and cardiovascular disease

Cotter

Schugar

Crawford

2013

American Journal of Physiology-Heart and Circulatory Physiology

374

304

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Ketone bodies are metabolized through evolutionarily conserved pathways that support bioenergetic homeostasis, particularly in brain, heart, and skeletal muscle when carbohydrates are in short supply. The metabolism of ketone bodies interfaces with the tricarboxylic acid cycle, β-oxidation of fatty acids, de novo lipogenesis, sterol biosynthesis, glucose metabolism, the mitochondrial electron transport chain, hormonal signaling, intracellular signal transduction pathways, and the microbiome. Here we review the mechanisms through which ketone bodies are metabolized and how their signals are transmitted. We focus on the roles this metabolic pathway may play in cardiovascular disease states, the bioenergetic benefits of myocardial ketone body oxidation, and prospective interactions among ketone body metabolism, obesity, metabolic syndrome, and atherosclerosis. Ketone body metabolism is noninvasively quantifiable in humans and is responsive to nutritional interventions. Therefore, further investigation of this pathway in disease models and in humans may ultimately yield tailored diagnostic strategies and therapies for specific pathological states.

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“…During periods of limited availability of carbohydrates or when carbohydrates cannot be used effectively, ketolysis enables fat-derived energy to be used by such organs as the heart, kidney, skeletal muscle, and brain. Studies have demonstrated an impaired utilization of ketone bodies in diabetes (15,25) and decreased 3-ketoacid CoA-transferase activity (13,14).…”

mentioning

confidence: 99%

Physical training reverses defect in 3-ketoacid CoA-transferase activity in skeletal muscle of diabetic rats

Midaoui

Chiasson²,

Tancrède³

et al. 2005

American Journal of Physiology-Endocrinology and Metabolism

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. Physical training reverses defect in 3-ketoacid CoAtransferase activity in skeletal muscle of diabetic rats. Am J Physiol Endocrinol Metab 288: E748 -E752, 2005; doi:10.1152/ajpendo.00515. 2004.-To investigate one potential mechanism whereby physical training improves the plasma concentration of ketone bodies in experimental diabetes mellitus, we measured the activity of 3-ketoacid CoA-transferase, the key enzyme in the peripheral utilization of ketone bodies. Diabetes was induced with streptozotocin (50 mg/kg) and training carried out on a treadmill with a progressive 10-wk program. Diabetes resulted in an increase (P Ͻ 0.001) in plasma concentration of ␤-hydroxybutyric acid in sedentary rats, which was partly reversed by training (P Ͻ 0.001). Diabetes was also associated with a decreased activity of 3-ketoacid CoA-transferase in gastrocnemius muscle. When expressed per total gastrocnemius, training increased the activity of 3-ketoacid CoA-transferase by 66% in nondiabetic rats (P Ͻ 0.001) and by 150% in diabetic rats (P Ͻ 0.001), the decrease present in diabetic rats being fully reversed by training. Simple linear regression between the log of 3-ketoacid CoA-transferase activity and the log of plasma ␤-hydroxybutyric acid levels showed a statistically significant (r ϭ 0.563, P Ͻ 0.001) negative correlation. The beneficial effects of training on plasma ketone bodies in diabetic rats are probably explained, at least in part, by an increase in ketone body utilization, mediated by an increase in skeletal muscle 3-ketoacid CoA-transferase activity.

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Ketone Body Utilization and Its Metabolic Effect in Resting Muscles of Normal and Streptozotocin-Diabetic Rats.

Cited by 14 publications

References 16 publications

Multi-dimensional Roles of Ketone Bodies in Fuel Metabolism, Signaling, and Therapeutics

Multi-dimensional Roles of Ketone Bodies in Fuel Metabolism, Signaling, and Therapeutics

Ketone body metabolism and cardiovascular disease

Physical training reverses defect in 3-ketoacid CoA-transferase activity in skeletal muscle of diabetic rats

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