Training Adaptations - Ketogenesis/Ketolysis

Endurance training causes a number of of adaptations in athletes, most of the attention has been placed on the enhanced delivery and utilisation of circulating carbohydrate and fat. Less is known about the adaptations relating to ketone body metabolism (ketogenesis - production and ketolysis - breakdown). 

The enzymes involved in ketogensis in the liver (BDH/ACAT/HMGCS) are unaltered as a result of athletic training and the overall activity of the pathway may even be lower. The activity of enzymes involved in ketolysis (BDH/OXCT/ACAT) are higher in skeletal muscle after 8-12 weeks of endurance training. When physiologically relevant amounts of BHB and AcAc (0.5mM and 1.0mM) are added to perfused muscle homogenates, their oxidation is increased by 2-3 fold. 

Ketogensis/Ketolysis pathways - Activity increased by endurance training indicated by +
From Evans et al (2016) - Journal of Physiology

While much of this work has been conducted in rats, it still has applications in a human model. The difference in trained and untrained humans being the rise in post exercise ketosis. We see attenuated ketosis in trained humans while untrained individuals experience an amplified level of ketosis up to 2.0mM i.e. acitivty of ketogenic pathway is lower and ketolysis is higher in trained individuals. 

From Walton (1972) - Journal of Experimental Physiology

Changes in ketolytic enzymes can also be detected in each muscle fibre type. Activity is highest in all enzymes in oxidative type 1 muscle fibres and lowest in type IIA and IIB fibres. 12 weeks of endurance training increased BDH activity in type 1 fibres threefold. OXCT and ACAT activity was increased by 26% and 40% respectively. These changes in ketolytic enzymes are localised to skeletal muscle and do not occur in the heart, kidney or brain. The transport of ketone bodies occurs via MCT1 transporters, a protein expressed highest in type 1 muscle fibres and is increased through exercise training. 

With this data in mind, increasing circulating ketone bodies through exogenous supplementation will likely benefit those who are aerobically trained with a high percentage of type I muscle fibres. These types of athletes usually compete endurance events such as long distance cycling and running. 

Next: Ketone Body Supplementation

References: 

Askew EW, Dohm GL & Huston RL (1975). Fatty acid and ketone body metabolism in the rat: response to diet and exercise. J Nutr 105, 1422–1432. 

Beattie MA & Winder WW (1984). Mechanism of training-induced attenuation of postexercise ketosis. Am J Physiol Regul Integr Comp Physiol 247, R780–R785. 

El Midaoui A, Chiasson JL, Tancrede G & Nadeau A (2006). Physical training reverses the increased activity of the hepatic ketone body synthesis pathway in chronically diabetic rats. Am J Physiol Endocrinol Metab 290, E207–E212. 

Johnson RH & Walton JL (1972). The effect of exercise upon acetoacetate metabolism in athletes and non-athletes. Q J Exp Physiol Cogn Med Sci 57, 73–79. 

Winder WW, Baldwin KM & Holloszy JO (1973). Exercise-induced adaptive increase in rate of oxidation of β-hydroxybutyrate by skeletal muscle. Proc Soc Exp Biol Med 143, 753–755. 

Winder WW, Baldwin KM & Holloszy JO (1974). Enzymes involved in ketone utilization in different types of muscle: adaptation to exercise. Eur J Biochem 47, 461–467.

Winder WW, Baldwin KM & Holloszy JO (1975). Exercise-induced increase in the capacity of rat skeletal muscle to oxidize ketones. Can J Physiol Pharmacol 53, 86–91