Optimising training and performance through nutrition strategies is central to supporting elite sportspeople, much of which has focused on manipulating the relative intake of carbohydrate and fat and their contributions as fuels for energy provision. The ketone bodies, namely acetoacetate, acetone and β-hydroxybutyrate (βHB), are produced in the liver during conditions of reduced carbohydrate availability and serve as an alternative fuel source for peripheral tissues including brain, heart and skeletal muscle. Ketone bodies are oxidised as a fuel source during exercise, are markedly elevated during the post-exercise recovery period, and the ability to utilise ketone bodies is higher in exercise-trained skeletal muscle. The metabolic actions of ketone bodies can alter fuel selection through attenuating glucose utilisation in peripheral tissues, anti-lipolytic effects on adipose tissue, and attenuation of proteolysis in skeletal muscle. Moreover, ketone bodies can act as signalling metabolites, with βHB acting as an inhibitor of histone deacetylases, an important regulator of the adaptive response to exercise in skeletal muscle. Recent development of ketone esters facilitates acute ingestion of βHB that results in nutritional ketosis without necessitating restrictive dietary practices. Initial reports suggest this strategy alters the metabolic response to exercise and improves exercise performance, while other lines of evidence suggest roles in recovery from exercise. The present review focuses on the physiology of ketone bodies during and after exercise and in response to training, with specific interest in exploring the physiological basis for exogenous ketone supplementation and potential benefits for performance and recovery in athletes.
The edg-1 gene encodes an inducible G protein-coupled receptor (GPR) homologue that is induced during the in vitro differentiation of human endothelial cells. The aim of this study was to investigate the G proteincoupling and -signaling properties of the edg-1 polypeptide. The third cytosolic loop (i 3 ) of edg-1 associates with G i␣ and G o␣ polypeptides in a guanosine 5-O-(thiotriphosphate)-sensitive manner. Immunoprecipitation of the edg-1 polypeptide in transfected cells results in the co-precipitation of G i␣1 and G i␣3 polypeptides. These data strongly suggest that edg-1 is capable of coupling to the G i pathway. Overexpression of the edg-1 GPR in human embryonic kidney 293 cells results in the sustained activation of the MAP kinase activity that is blocked by pertussis toxin treatment. Moreover, NIH3T3 cells permanently transfected with edg-1 exhibit enhanced MAP kinase and phospholipase A 2 activities. These data suggest that the G i /mitogen-activated protein kinase pathway is a major signaling pathway regulated by the orphan receptor edg-1.
Purpose Preexercise ingestion of exogenous ketones alters the metabolic response to exercise, but effects on exercise performance have been equivocal. Methods On two occasions in a double-blind, randomized crossover design, eight endurance-trained runners performed 1 h of submaximal exercise at approximately 65% V˙O2max immediately followed by a 10-km self-paced time trial (TT) on a motorized treadmill. An 8% carbohydrate-electrolyte solution was consumed before and during exercise, either alone (CHO + PLA), or with 573 mg·kg−1 of a ketone monoester supplement (CHO + KME). Expired air, HR, and RPE were monitored during submaximal exercise. Serial venous blood samples were assayed for plasma glucose, lactate, and β-hydroxybutyrate concentrations. Results CHO + KME produced plasma β-hydroxybutyrate concentrations of approximately 1.0 to 1.3 mM during exercise (P < 0.001), but plasma glucose and lactate concentrations were similar during exercise in both trials. V˙O2, running economy, respiratory exchange ratio, HR, and RPE were also similar between trials. Performance in the 10-km TT was not different (P = 0.483) between CHO + KME (mean, 2402 s; 95% confidence interval, 2204–2600 s) and CHO + PLA (mean, 2422 s; 95% confidence interval, 2217–2628 s). Cognitive performance, measured by reaction time and a multitasking test, did not differ between trials. Conclusions Compared with carbohydrate alone, coingestion of KME by endurance-trained athletes elevated plasma β-hydroxybutyrate concentrations, but did not improve 10-km running TT or cognitive performance.
These results show that episomal HPV can be reliably determined by NISH type 1 signal, integrated HPV by type 2, and a combination of both episomal and integrated HPV, by a type 3 signal in archival paraffin wax embedded cervical biopsy specimens. This will add another variable to the epidemiological studies of HPV infection. In particular, it will now allow retrospective studies to be done to define the role ofepisomal and integrated HPV in the evolution of cervical intraepithelial neoplasia and other cervical disease associated with this virus.
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